JP2001131137A - Peptide mimetic template - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a peptide mimetic template. SOLUTION: This compound is represented by the general formula (I) [wherein Ar is an aryl group; R1 and R2 are each H or a protecting group of amino group; R is hydrogen atom or a lower alkyl group; R4 is an amine residue or a group having the formula O-R7 (wherein R7 is H or an ester residue); R5 is hydrogen atom; n is 1-4; and R6 is hydroxy when the broken line is a single bond or R6 is oxygen atom when the broken line is a double bond] or a base addition salt or an acid addition salt thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a compound useful as a template for the synthesis of peptidomimetics, or a base or acid addition salt thereof, a peptidomimetic template composed of the compound, and the above-described peptidomimetic template incorporated therein. And a peptide mimetic library comprising a plurality of the above peptide mimetics.

[0002]

BACKGROUND OF THE INVENTION Proteins are involved in all biological processes involved in the expression of genetic information, including the transcription, translation and post-translational modification of genes, and are required for the functions required to ultimately embody the genetic information, It is a very important biological molecule with information and structure.

[0003] Proteins play a wide variety of biological roles as enzymes, secretory proteins (bioactive small peptides), membrane receptor proteins, transport proteins, defense proteins, motor proteins, structural proteins, nutritional proteins and the like. It is responsible for maintaining the body's homeostasis.

[0004] It is thought that many diseases are caused by qualitative or imbalance in these proteins and bioactive peptides. Therefore, proteins and physiologically active peptides involved in diseases have provided abundant resources as important targets for drug development.

[0005] However, the protein itself has a low biological absorption, oral activity, membrane permeability, unfavorable pharmacokinetics, antigenicity, dosage form for patients (injection, infusion, etc.).
There are various problems in developing as a medicament, such as restrictions and demands originated from.

[0006] Proteins often express their biological activity through a small region of secondary structure on the folded structural surface, and their function is, in principle, to maintain the active surface well. It is thought to be reproduced by a relatively small molecule (peptide mimetic) designed in U.S. Pat.

[0007] The above-mentioned problems of proteins and physiologically active peptides as pharmaceuticals are often derived from peptide bonds constituting the protein. Therefore, they imitate the biologically active region of the protein and make its structure and function non-functional. Numerous peptidomimetics have been devised to replace low molecular weight peptidic compounds [DP Fairli
e, Current Med. Chem., 1998, 5, GJ Moore, Advanc
es in Pharmacol., 1995, 33, 91].

However, many of the templates that have been developed so far are complex ones that require many steps to be synthesized, or can be used only as mimetics of some amino acids, or if the template is incorporated, the amino acid It has a drawback that the original activity is significantly reduced, and the degree of completion as a template is poor.

[0009] Therefore, a template which can form mimetics of various amino acids with a wide range of selection of substituents, has high versatility, and can be obtained by an easier process than conventional ones is desired. I was

As prior art relating to the present invention, for example, in the structural formula of compound (I) of the present invention, R ³ is a methyl group, R ⁴ is a methoxy group, a broken line indicates a single bond, and R ⁶ is The compound which is an oxygen atom is disclosed in JP-A-52-1.
No. 7432 discloses a compound in which R ³ is a parahydroxybenzyl group, R ⁴ is a hydroxy group, a broken line indicates a single bond, and R ⁶ is an oxygen atom.
No. 0 discloses this.

However, the compound (I) of the present invention
When R ³ is a methyl group, R ⁴ represents a group other than a methoxy group, and when R ³ is para-hydroxy benzyl group, R ⁴ is a point that indicates a group other than hydroxy group,
JP-A-52-17432 and WO94 / 00
No. 420, different from the compound disclosed, further,
The use as a peptidomimetic template is not disclosed or suggested in the above publication.

[0012]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive studies on the synthesis and physiological activity of a template for peptide mimetic synthesis over many years, and as a result, the synthesis is easy and versatile. Find the compound of the present invention,
The present invention has been completed.

Still another object of the present invention is to provide a peptidomimetic template comprising the compound of the present invention, a peptidomimetic obtained by incorporating the peptidomimetic template, and a peptidomimetic comprising a plurality of the peptidomimetics. To provide a tick library.

[0014]

Means for Solving the Problems (1) The compound of the present invention has the general formula (I).

[0015]

Embedded image [In the formula, Ar represents an aryl group or a heteroaryl group, and R ¹ and R ² are the same or different and each is a group selected from a hydrogen atom, a lower alkyl group, an aryl group, and a substituent group a. Represents a 3-substituted protecting group for an aryl group or an amino group, and R ³ is selected from a hydrogen atom, a lower alkyl group, a heteroaryl group, an aralkyl group, a heteroaryl lower alkyl group, and a substituent group a. Represents a lower alkyl group, a heteroaryl group, an aralkyl group or a heteroaryl lower alkyl group substituted by 1 to 3 groups, or a nitrogen atom adjacent to the carbon atom to which R ³ is bonded and R ³ May together form a ring, and R ⁴ represents an amine residue or a group having the formula —O—R ⁷ , wherein R ⁷ represents a hydrogen atom or an ester residue. But However, when R ³ is a methyl group, R ⁴ is not a methoxy group, and when R ³ is a parahydroxybenzyl group, R ⁴ is not a hydroxy group.
⁵ is a hydrogen atom, a lower alkyl group, an aryl group, an aralkyl group, a group selected from substituent group a, or a lower alkyl group substituted with 1 to 3 groups selected from substituent group a, aryl A group or an aralkyl group, n represents an integer of 1 to 4, provided that when n represents an integer of 2 or more, R ⁵ represents the same or different groups, and R ⁶ represents a single bond. Is a hydroxy group, and when the dashed line represents a double bond, R ⁶ is an oxygen atom;
Is a hydroxy group, a lower alkoxy group, an aryloxy group, an aralkyloxy group, a mercapto group, a lower alkylthio group, an arylthio group, an aralkylthio group, a formyl group, a lower alkylcarbonyl group, an arylcarbonyl group, an aralkylcarbonyl group, a carboxy group, Lower alkoxycarbonyl group, aryloxycarbonyl group, aralkyloxycarbonyl group, (mono- or di-substituted by a group selected from the group consisting of lower alkyl, aryl, aralkyl, carboxy, lower alkoxycarbonyl, aryloxycarbonyl and aralkyloxycarbonyl An amino group, which may be
(It may be mono- or di-substituted with a group selected from the group consisting of aryl and aralkyl.) Carbamoyl, amidino, guanidino, cyano, halogen, nitro, sulfo, and halogenoalkyl groups. ].

Among these, preferred compounds include
(2) a compound wherein the dashed line represents a double bond and R ⁶ is an oxygen atom, (3) a compound wherein a dashed line represents a single bond and the R ⁶ is a hydroxy group, (4) Ar is benzene, pyridine, A compound which is quinoline or thiophene, (5)
A compound in which R ¹ is a hydrogen atom, (6) a compound in which R ² is a protecting group for an amino group, (7) a compound in which R ³ is a hydrogen atom, lower alkyl, aralkyl, heteroaryl lower alkyl, or substituent group a 1 is three substituted with a group selected lower alkyl, aralkyl or heteroaryl-lower alkyl group, or a nitrogen atom and R ³ which is adjacent to the carbon atom to which R ³ is attached is a pyrrolidine ring or a piperidine ring Compound to be formed, (8) R ³ is a hydrogen atom, methyl, ethyl, propyl, isopropyl, isobutyl, benzyl, 2-methylthioethyl, 4- (benzyloxycarbonylamino) butyl, 4-benzyloxybenzyl, t-butoxy Carbonylmethyl, 1-
(T-butoxycarbonyl) ethyl, 2- (t-butoxycarbonyl) ethyl or 3-indolylmethyl, or a nitrogen atom adjacent to the carbon atom to which R ³ is bonded and R ³ are pyrrolidine rings Or a compound forming a piperidine ring, (9) a compound in which the configuration at the skeleton carbon to which R ³ is bonded is a configuration derived from a natural amino acid, (10) a compound wherein n is 1, (11)
A compound wherein R ⁵ is a hydrogen atom. (12) The present invention further provides a peptidomimetic template comprising a compound having the following general formula (II), a peptidomimetic obtained by incorporating the peptidomimetic template, and a peptide comprising a plurality of the peptidomimetics It provides a mimetic library.

[0017]

Embedded image [In the formula, Ar represents an aryl group or a heteroaryl group, and R ¹ and R ² are the same or different and each is a group selected from a hydrogen atom, a lower alkyl group, an aryl group, and a substituent group a. R ^3a represents a hydrogen atom, a lower alkyl group, an aryl group, a heteroaryl group, an aralkyl group, a heteroaryl lower alkyl group, or a substituent group a Represents a lower alkyl group, an aryl group, a heteroaryl group, an aralkyl group, or a heteroaryl lower alkyl group substituted by 1 to 3 groups selected with, or adjacent to the carbon atom to which R ^3a is bonded. The nitrogen atom and R ^3a may together form a ring, wherein R ⁴ is an amine residue or a group having the formula —O—R ⁷ , wherein R ⁷ is
Represents a hydrogen atom or an ester residue. ) And R
⁵ is a hydrogen atom, a lower alkyl group, an aryl group, an aralkyl group, a group selected from substituent group a, or a lower alkyl group substituted with 1 to 3 groups selected from substituent group a, aryl A group or an aralkyl group, n represents an integer of 1 to 4, provided that when n represents an integer of 2 or more, R ⁵ represents the same or different groups, and R ⁶ represents a single bond. Is a hydroxy group, and when the dashed line represents a double bond, R ⁶ is an oxygen atom;
Is a hydroxy group, a lower alkoxy group, an aryloxy group, an aralkyloxy group, a mercapto group, a lower alkylthio group, an arylthio group, an aralkylthio group, a formyl group, a lower alkylcarbonyl group, an arylcarbonyl group, an aralkylcarbonyl group, a carboxy group, Lower alkoxycarbonyl group, aryloxycarbonyl group, aralkyloxycarbonyl group, (mono- or di-substituted by a group selected from the group consisting of lower alkyl, aryl, aralkyl, carboxy, lower alkoxycarbonyl, aryloxycarbonyl and aralkyloxycarbonyl An amino group, which may be
(It may be mono- or di-substituted with a group selected from the group consisting of aryl and aralkyl.) Carbamoyl, amidino, guanidino, cyano, halogen, nitro, sulfo, and halogenoalkyl groups. ].

Of these, preferred compounds include
(13) a compound wherein the dashed line represents a double bond and R ⁶ is an oxygen atom, (14) a compound wherein a dashed line represents a single bond and the R ⁶ is a hydroxy group, (15) Ar is benzene, pyridine, A compound which is quinoline or thiophene, (16) a compound wherein R ¹ is a hydrogen atom, (17)
(18) a compound wherein R ² is a protecting group for an amino group,
^3a is a hydrogen atom, lower alkyl, aralkyl, heteroaryl lower alkyl, or a group selected from substituent group a by 1 to 3 substituents, lower alkyl, aralkyl or heteroaryl lower alkyl group, or R ^3a is A compound in which a nitrogen atom adjacent to a bonded carbon atom and R ^3a form a pyrrolidine ring or a piperidine ring, (1
9) R ^3a represents a hydrogen atom, methyl, ethyl, propyl,
Isopropyl, isobutyl, benzyl, 2-methylthioethyl, 4- (benzyloxycarbonylamino) butyl, 4-benzyloxybenzyl, t-butoxycarbonylmethyl, 1- (t-butoxycarbonyl) ethyl,
2-(t-butoxycarbonyl) ethyl or 3-in or drilling a methyl group, or a compound and a nitrogen atom R ^3a adjacent to the carbon atom R ^3a are attached to form a pyrrolidine ring or a piperidine ring, (20) a compound in which the configuration at the skeleton carbon to which R ^3a is bonded is a configuration derived from a natural amino acid; (21) a compound wherein n is 1; and (22) a compound wherein R ⁵ is a hydrogen atom.

In the above formula, 1 to 3 substituents are selected from Ar, R ¹ , R ² , R ^3a , R ⁵ and the group selected from “aryl group” and “substituent group a” in the definition of substituent group a. The aryl portion of the "aryl group" may be, for example, an aromatic hydrocarbon group having 6 to 10 carbon atoms such as phenyl, indenyl, and naphthyl, and is preferably a phenyl or naphthyl group, and most preferably Is a phenyl group.

In the above formula, a group selected from “heteroaryl group”, “heteroaryl lower alkyl group” and “substituent group a” in the definition of Ar, R ³ and R ^3a is 1 to 3
The heteroaryl portion of the “substituted heteroaryl lower alkyl group” represents a 5- to 7-membered heterocyclic group containing 1 to 3 sulfur atoms, oxygen atoms and / or nitrogen atoms, for example, furyl, thienyl, pyrrolyl, Azepinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl,
Examples include aromatic heterocyclic groups such as thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, and pyrazinyl. Further, the heteroaryl group may be condensed with another cyclic group such as a benzene ring, for example, benzothienyl, benzothiazolyl, benzoxazolyl, isobenzofuranyl, chromenyl, xanthenyl,
Mention may be made of groups such as phenoxathiinyl, indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolidinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, carbazolyl, carbolinyl, acridinyl, isoindolinyl. In such a heterocyclic group, a 5- or 6-membered aromatic heterocyclic group or a 5- or 6-membered aromatic heterocyclic group condensed with a benzene ring is preferable, and thienyl, furyl, pyrrolyl, Thiazolyl, oxazolyl, imidazolyl, pyridyl or a thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl or pyridyl group fused to a benzene ring, most preferably a pyridyl, quinolyl or thienyl group.

In the above formula, R¹, R^Two, R^Three, R^3a, R^Fiveas well as
“Lower alkyl group” and “hetero group” in the definition of substituent group a
Lower arylalkyl group "," substituent group a "
A lower alkyl group substituted with 1 to 3 groups by
"1 to 3 substituted with a group selected from the substituent group a
Lower alkyl moiety of "heteroaryl lower alkyl group"
Is, for example, methyl, ethyl, propyl, isopropyl
Butyl, isobutyl, s-butyl, t-butyl,
Pentyl, isopentyl, 2-methylbutyl, neopent pentyl
1-ethylpropyl, hexyl, isohexyl, 4
-Methylpentyl, 3-methylpentyl, 2-methylpetyl
Methyl, 1-methylpentyl, 3,3-dimethylbuty
1,2-dimethylbutyl, 1,1-dimethylbutyl
1,2-dimethylbutyl, 1,3-dimethylbutyl
2,3-dimethylbutyl and 2-ethylbutyl groups
A linear or branched alkyl group having 1 to 6 carbon atoms
And preferably C ₁-C_FourAlkyl group, more preferably
Is methyl, ethyl, propyl, isopropyl or iso
Butyl, most preferably methyl, ethyl or
It is a ropyl group.

In the above formula, the term "protecting group for amino group" in the definition of R ¹ and R ² means a protecting group for amino group generally used in the field of synthetic organic chemistry. , Acetyl, propionyl, butyryl, isobutyryl, pentanoyl, pivaloyl, valeryl, isovaleryl, octanoyl, nonanoyl, decanoyl, 3-methylnonanoyl, 8-methylnonanoyl, 3-ethyloctanoyl, 3,7-dimethyloctanoyl, undecanoyl, dodecanoyl, tridecanoyl , Tetradecanoyl, pentadecanoyl, hexadecanoyl, 1-methylpentadecanoyl, 14-methylpentadecanoyl, 1
Lower alkylcarbonyl groups such as 3,13-dimethyltetradecanoyl, heptadecanoyl, 15-methylhexadecanoyl, octadecanoyl, 1-methylheptadecanoyl, nonadecanoyl, eicosanoyl, henicosanoyl, chloroacetyl, dichloroacetyl, trichloroacetyl "Aliphatic acyls" such as halogeno lower alkylcarbonyl groups such as trifluoroacetyl and lower alkoxycarbonyl groups substituted by lower alkoxy such as methoxyacetyl; benzoyl such as benzoyl, α-naphthoyl and β-naphthoyl Halogenoarylcarbonyl groups such as 1,1-indanecarbonyl, 2-indancarbonyl, 1- or 2-naphthoyl, lower alkyls such as 2,4,6-trimethylbenzoyl and 4-toluoyl; Arylcarbonyl group substituted with lower alkoxy such as 4-anisoyl, 4-nitrobenzoyl,
Arylcarbonyl groups substituted by nitro, such as -nitrobenzoyl; arylcarbonyl groups substituted by lower alkoxycarbonyl, such as 2- (methoxycarbonyl) benzoyl; arylcarbonyl substituted by aryl, such as 4-phenylbenzoyl "Aromatic acyls" such as a group; methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, s
-Butoxycarbonyl, t-butoxycarbonyl, pentoxycarbonyl, isopentoxycarbonyl, 2-methylbutoxycarbonyl, neopentoxycarbonyl,
Hexyloxycarbonyl, 4-methylpentoxycarbonyl, 3-methylpentoxycarbonyl, 2-methylpentoxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 1,1
Lower alkoxycarbonyl groups such as -dimethylbutoxycarbonyl, 1,2-dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl, 2,3-dimethylbutoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl, 2-trimethylsilyl "Alkoxycarbonyls" such as lower alkoxycarbonyl groups substituted by halogen or tri-lower alkylsilyl such as ethoxycarbonyl; "alkenyloxycarbonyls" such as vinyloxycarbonyl and allyloxycarbonyl; benzyloxycarbonyl; "1" such as methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl
Aralkyloxycarbonyls in which the aryl ring may be substituted with up to two lower alkoxy or nitro ";
Tri-lower alkylsilyl groups such as trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-t-butylsilyl, triisopropylsilyl, diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl, phenyl "Silyls" such as silyl groups tri-substituted with aryl or aryl and lower alkyl such as diisopropylsilyl; benzyl, phenethyl, 3-phenylpropyl,
lower alkyl group substituted with 1 to 3 aryl groups such as α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthrylmethyl, 4-methylbenzyl , 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl,
Lower alkyl such as -nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, 4-cyanobenzyldiphenylmethyl, bis (2-nitrophenyl) methyl, piperonyl, lower alkoxy, nitro, halo or cyano 1-3 wherein the aryl ring is substituted with
"Aralkyls" such as lower alkyl groups substituted with two aryl groups; N, N-dimethylaminomethylene, benzylidene, 4-methoxybenzylidene, 4-nitrobenzylidene, salicylidene, 5-chlorosalicylidene, diphenylmethylene , (5-chloro-2-hydroxyphenyl) phenylmethylene, such as "substituted methylene groups forming a Schiff base", preferably with alkoxycarbonyls or one or two lower alkoxy or nitro groups. Aralkyloxycarbonyls in which the aryl ring may be substituted.

In the above formula, R ³ , R ^3a , R ⁵ and the substituent group a
The aralkyl moiety of the `` aralkyl group '' and the `` aralkyl group substituted by a group selected from the substituent group a '' in the definition of benzyl, α-naphthylmethyl, β-naphthylmethyl, indenylmethyl, diphenylmethyl,
Triphenylmethyl, 1-phenethyl, 2-phenethyl, 1-naphthylethyl, 2-naphthylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, 1-naphthylpropyl, 2-naphthylpropyl, 3-naphthyl Propyl, 1-phenylbutyl, 2-
Phenylbutyl, 3-phenylbutyl, 4-phenylbutyl, 1-naphthylbutyl, 2-naphthylbutyl, 3-
Naphthylbutyl, 4-naphthylbutyl, 1-phenylpentyl, 2-phenylpentyl, 3-phenylpentyl, 4-phenylpentyl, 5-phenylpentyl, 1
-Naphthylpentyl, 2-naphthylpentyl, 3-naphthylpentyl, 4-naphthylpentyl, 5-naphthylpentyl, 1-phenylhexyl, 2-phenylhexyl, 3-phenylhexyl, 4-phenylhexyl, 5
A C ₇ -C ₁₆ aralkyl group such as -phenylhexyl, 6-phenylhexyl, 1-naphthylhexyl, 2-naphthylhexyl, 3-naphthylhexyl, 4-naphthylhexyl, 5-naphthylhexyl or 6-naphthylhexyl; And preferably a benzyl group.

In the above formula, a ring formed by “the nitrogen atom adjacent to the carbon atom to which R ³ is bonded and R ³ together” or “the ring adjacent to the carbon atom to which R ^3a is bonded” The ring formed by the nitrogen atom and R ^3a together is:
For example, aziridine, pyrrolidine, piperidine, morpholine, piperazine, thiomorpholine, thiazolidine, homopiperidine can be mentioned, and preferred is pyrrolidine or piperidine.

In the above formula, the "amine residue" in the definition of R ⁴ is, for example, an amino group; methylamino group, ethylamino, isopropylamino, butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, diisopropyl "An amino group in which one or two lower alkyl groups are substituted" such as amino, dibutylamino and dipentylamino; a cycloalkyl group having 5 to 7 carbon atoms such as cyclopentylamino, cyclohexylamino, dicyclopentylamino and dicyclohexylamino Is an amino group substituted by 1 or 2 groups; pyrrolidino, piperidino, piperazino, N-methylpiperazino, morpholino,
"Saturated cyclic amine residue having a nitrogen atom in the ring" such as thiomorpholino; anilino, 2-carboxyanilino, 3-carboxyanilino, 4-carboxyanilino, 2-methoxycarbonylanilino, 3-methoxy Carbonylanilino, 4-methoxycarbonylanilino,
2-ethoxycarbonylanilino, 3-ethoxycarbonylanilino, 4-ethoxycarbonylanilino, 2-
Propoxycarbonylanilino, 3-propoxycarbonylanilino, 4-propoxycarbonylanilino, benzylamino, 2-carboxybenzylamino, 3-carboxybenzylamino, 4-carboxybenzylamino, 2-methoxycarbonylbenzylamino, 3-methoxy Carbonylbenzylamino, 4-methoxycarbonylbenzylamino, 2-ethoxycarbonylbenzylamino, 3-ethoxycarbonylbenzylamino, 4-ethoxycarbonylbenzylamino, 2-propoxycarbonylbenzylamino, 3-propoxycarbonylbenzylamino, 4-propoxycarbonyl An “arylamino or aralkylamino group optionally substituted with a carboxy group or a lower alkoxycarbonyl group”, such as benzylamino; "Aryl or aralkylamino groups in which a nitrogen atom is substituted with a lower alkyl group" such as methylanilino and N-methylbenzylamino; An amine residue bonded with a nitrogen atom such as a heteroarylamino group which may be substituted with
Preferably, an amino group, an amino group substituted with one or two lower alkyl groups, a saturated cyclic amine residue having a nitrogen atom in the ring, and an aryl or aralkyl optionally substituted with a nitrogen atom by a lower alkyl group An amino group can be mentioned, and preferably, "an amino group substituted by one or two lower alkyl groups", "saturated cyclic amine residue having a nitrogen atom in the ring" or "carboxy group or lower alkoxycarbonyl group" And an arylamino group or an aralkylamino group which may be substituted, and most preferably an "amino group substituted with one or two lower alkyl groups".

In the above formula, the term "ester residue" in the definition of R ⁷ means an atomic group which forms an ester by bonding to the acyloxy group, and is preferably one which is released by an enzyme in the body. For example, the lower alkyl group, phenyl, tolyl, ethylphenyl, methoxyphenyl,
Aryl group optionally substituted with lower alkyl such as fluorophenyl and chlorophenyl, lower alkoxy or halogen, substituted with lower alkyl such as benzyl, ethylbenzyl, methoxybenzyl, fluorobenzyl and chlorobenzyl, lower alkoxy or halogen Aralkyl, phthaldyl, pivaloyloxymethyl, 1-ethoxycarbonyloxymethyl, 5-methyl-2-oxo-1,3-dioxolen-
4-ylmethyl, 5-phenyl-2-oxo-1,3-
Dioxolen-4-ylmethyl and the like can be mentioned, preferably a lower alkyl group or an aralkyl group optionally substituted by lower alkyl, lower alkoxy or halogen, and most preferably a methyl or benzyl group.

In the above formula, the “lower alkoxy group” in the definition of the substituent group “a” indicates a group in which the above “lower alkyl group” is bonded to an oxygen atom, for example, methoxy, ethoxy,
Propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, pentoxy, isopentoxy, 2-methylbutoxy, neopentoxy, hexyloxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 3 Carbon atoms such as 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, and 2,3-dimethylbutoxy;
From 6 to 6 linear or branched alkoxy groups, preferably C ₁ -C ₄ alkoxy groups, more preferably C ₁ -C ₂ alkoxy groups.
An alkoxy group, most preferably a methoxy group.

In the above formula, the “aryloxy group” in the definition of the substituent group “a” indicates a group in which the above “aryl group” is bonded to an oxygen atom, for example, phenoxy, 1-indenyloxy, 2-indenyl An oxy, 1-naphthyloxy and 2-naphthyloxy group, preferably a phenoxy group.

In the above formula, the “aralkyloxy group” in the definition of the substituent group “a” indicates a group in which the above “aralkyl group” is bonded to an oxygen atom, for example, benzyloxy, α-
Naphthylmethoxy, β-naphthylmethoxy, indenylmethoxy, diphenylmethoxy, triphenylmethoxy, 1-phenethyloxy, 2-phenethyloxy,
-Naphthylethoxy, 2-naphthylethoxy, 1-phenylpropoxy, 2-phenylpropoxy, 3-phenylpropoxy, 1-naphthylpropoxy, 2-naphthylpropoxy, 3-naphthylpropoxy, 1-phenylbutoxy, 2-phenylbutoxy, -Phenylbutoxy, 4-phenylbutoxy, 1-naphthylbutoxy, 2
-Naphthylbutoxy, 3-naphthylbutoxy, 4-naphthylbutoxy, 1-phenylpentyloxy, 2-phenylpentyloxy, 3-phenylpentyloxy,
-Phenylpentyloxy, 5-phenylpentyloxy, 1-naphthylpentyloxy, 2-naphthylpentyloxy, 3-naphthylpentyloxy, 4-naphthylpentyloxy, 5-naphthylpentyloxy, 1-phenylhexyloxy, 2-phenyl Hexyloxy,
3-phenylhexyloxy, 4-phenylhexyloxy, 5-phenylhexyloxy, 6-phenylhexyloxy, 1-naphthylhexyloxy, 2-naphthylhexyloxy, 3-naphthylhexyloxy, 4-
A naphthylhexyloxy, 5-naphthylhexyloxy or 6-naphthylhexyloxy group, preferably
It is a benzyloxy group.

In the above formula, the “lower alkylthio group” in the definition of the substituent group “a” refers to a group in which the above “lower alkyl group” is bonded to a sulfur atom, such as methylthio, ethylthio, propylthio, isopropylthio, butylthio,
Isobutylthio, s-butylthio, t-butylthio, pentylthio, isopentylthio, 2-methylbutylthio, neopentylthio, hexylthio, 4-methylpentylthio, 3-methylpentylthio, 2-methylpentylthio, 3,3 -Dimethylbutylthio, 2,2-dimethylbutylthio, 1,1-dimethylbutylthio, 1,2-
Dimethylbutylthio, 1,3-dimethylbutylthio,
1 to 6 carbon atoms such as 2,3-dimethylbutylthio group
Linear or branched alkylthio groups, preferably
An ₁ -C ₄ alkylthio group, more preferably a C ₁ -C ₂ alkylthio group, most preferably a methylthio group.

In the above formula, the “arylthio group” in the definition of the substituent group “a” indicates a group in which the above “aryl group” is bonded to a sulfur atom, for example, phenylthio, 1-indenylthio, 2-indenylthio, 3-indenylthio. , 1
-Naphthylthio or 2-naphthylthio, preferably phenylthio.

In the above formula, the “aralkylthio group” in the definition of the substituent group “a” indicates a group in which the above “aralkyl group” is bonded to a sulfur atom, such as benzylthio, α-naphthylmethylthio, β-naphthylmethylthio Indenylmethylthio, diphenylmethylthio, triphenylmethylthio, 1-phenethylthio, 2-phenethylthio,
-Naphthylethylthio, 2-naphthylethylthio, 1-
Phenylpropylthio, 2-phenylpropylthio, 3
-Phenylpropylthio, 1-naphthylpropylthio,
2-naphthylpropylthio, 3-naphthylpropylthio, 1-phenylbutylthio, 2-phenylbutylthio, 3-phenylbutylthio, 4-phenylbutylthio, 1-naphthylbutylthio, 2-naphthylbutylthio, 3- Naphthylbutylthio, 4-naphthylbutylthio, 1-phenylpentylthio, 2-phenylpentylthio, 3-phenylpentylthio, 4-phenylpentylthio, 5-phenylpentylthio, 1-naphthylpentylthio, 2-naphthylpentch Ruthio, 3-naphthylpentylthio, 4-naphthylpentylthio, 5-naphthylpentylthio, 1-phenylhexylthio, 2-phenylhexylthio, 3-phenylhexylthio, 4-phenylhexylthio, 5-phenylhexylthio, 6-phenylhexylthio, 1-na Hexyl thio, 2-
Naphthylhexylthio, 3-naphthylhexylthio, 4
-Naphthylhexylthio, 5-naphthylhexylthio or 6-naphthylhexylthio, preferably benzylthio.

In the above formula, the “lower alkylcarbonyl group” in the definition of the substituent group “a” has the same meaning as described above, and is preferably a C ₁ -C ₅ alkylcarbonyl group,
More preferably, it is a C ₁ -C ₃ alkylcarbonyl group, most preferably a formyl or acetyl group.

In the above formula, the “arylcarbonyl group” in the definition of the substituent group “a” has the same meaning as described above, and is preferably a benzoyl group.

In the above formula, the “aralkylcarbonyl group” in the definition of the substituent group “a” represents a group in which a carbonyl group is bonded to the above “aralkyl group”. Ryl, 5-phenylpentanoyl and 6-phenylhexanoyl, preferably phenylacetyl.

In the above formula, the “lower alkoxycarbonyl group” in the definition of the substituent group “a” has the same meaning as described above, and is preferably a C ₁ -C ₄ alkoxycarbonyl group, more preferably a C ₁ -C ₄ alkoxycarbonyl group. an ₁ -C ₂ alkoxycarbonyl group, most preferably a methoxycarbonyl group.

In the above formula, the “aryloxycarbonyl group” in the definition of the substituent group “a” represents a group in which a carbonyl group is bonded to the above “aryloxy group”, for example, phenoxycarbonyl, 1-indenyloxycarbonyl,
2-indenyloxycarbonyl, 1-naphthyloxycarbonyl, 2-naphthyloxycarbonyl group,
Preferably, it is a phenoxy group.

In the above formula, the “aralkyloxycarbonyl group” in the definition of the substituent group a indicates a group in which a carbonyl group is bonded to the “aralkyloxy group”.
Benzyloxycarbonyl, α-naphthylmethoxycarbonyl, β-naphthylmethoxycarbonyl, indenylmethoxycarbonyl, diphenylmethoxycarbonyl,
Triphenylmethoxycarbonyl, 1-phenethyloxycarbonyl, 2-phenethyloxycarbonyl, 1-
Naphthylethoxycarbonyl, 2-naphthylethoxycarbonyl, 1-phenylpropoxycarbonyl, 2-phenylpropoxycarbonyl, 3-phenylpropoxycarbonyl, 1-naphthylpropoxycarbonyl, 2-
Naphthylpropoxycarbonyl, 3-naphthylpropoxycarbonyl, 1-phenylbutoxycarbonyl, 2-
Phenylbutoxycarbonyl, 3-phenylbutoxycarbonyl, 4-phenylbutoxycarbonyl, 1-naphthylbutoxycarbonyl, 2-naphthylbutoxycarbonyl, 3-naphthylbutoxycarbonyl, 4-naphthylbutoxycarbonyl, 1-phenylpentyloxycarbonyl, 2-phenyl Pentyloxycarbonyl, 3-
Phenylpentyloxycarbonyl, 4-phenylpentyloxycarbonyl, 5-phenylpentyloxycarbonyl, 1-naphthylpentyloxycarbonyl, 2
-Naphthylpentyloxycarbonyl, 3-naphthylpentyloxycarbonyl, 4-naphthylpentyloxycarbonyl, 5-naphthylpentyloxycarbonyl,
1-phenylhexyloxycarbonyl, 2-phenylhexyloxycarbonyl, 3-phenylhexyloxycarbonyl, 4-phenylhexyloxycarbonyl, 5-phenylhexyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1-naphthylhexyloxycarbonyl, 2 -Naphthylhexyloxycarbonyl, 3-naphthylhexyloxycarbonyl, 4-naphthylhexyloxycarbonyl, 5-naphthylhexyloxycarbonyl or 6-naphthylhexyloxycarbonyl group, preferably a benzyloxycarbonyl group.

In the above formula, “substituted or di-substituted with a group selected from the group consisting of lower alkyl, aryl, aralkyl, carboxy, lower alkoxycarbonyl, aryloxycarbonyl and aralkyloxycarbonyl in the definition of substituent group a. Specific examples of the “amino group” include, for example, the “mono-lower alkylamino group”; the “di-lower alkylamino group”; phenylamino, 1-indenylamino, 2-indenylamino,
An amino group in which one or two of the above “aryl groups” are substituted, such as 1-naphthylamino and 2-naphthylamino; benzylamino, α-naphthylmethylamino, β-naphthylmethylamino, indenylmethylamino, diphenylmethylamino , Triphenylmethylamino, 1-phenethylamino, 2-phenethylamino, 1-naphthylethylamino, 2-naphthylethylamino, 1-phenylpropylamino, 2-phenylpropylamino, 3-phenylpropylamino, 1-naphthylpropyl An amino group in which one or two of the above “aralkyl groups” are substituted, such as amino, 2-naphthylpropylamino and 3-naphthylpropylamino; carboxyamino, methoxycarbonylamino,
Ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, isobutoxycarbonylamino, s-butoxycarbonylamino, t-butoxycarbonylamino, pentoxycarbonylamino, isopentoxycarbonylamino, 2-methylbutoxycarbonyl amino,
Neopentoxycarbonylamino, hexyloxycarbonylamino, 4-methylpentoxycarbonylamino, 3-methylpentoxycarbonylamino, 2-methylpentoxycarbonylamino, 3,3-dimethylbutoxycarbonylamino, 2,2-dimethylbutoxy Carbonylamino, 1,1-dimethylbutoxycarbonylamino, 1,2-dimethylbutoxycarbonylamino,
1,3-dimethylbutoxycarbonylamino, 2,3-
An amino group substituted by one or two of the above “carboxy or lower alkoxycarbonyl group” such as dimethylbutoxycarbonylamino; phenoxycarbonylamino, 1-
An amino group in which one or two of the aforementioned “aryloxycarbonyl groups” are substituted, such as indenyloxycarbonylamino, 2-indenyloxycarbonylamino, 1-naphthyloxycarbonylamino, and 2-naphthyloxycarbonylamino; benzyloxycarbonyl Amino, α-
Naphthylmethoxycarbonylamino, β-naphthylmethoxycarbonylamino, indenylmethoxycarbonylamino, diphenylmethoxycarbonylamino, triphenylmethoxycarbonylamino, 1-phenethyloxycarbonylamino, 2-phenethyloxycarbonylamino, 1-naphthylethoxycarbonylamino, 2-
Such as naphthylethoxycarbonylamino, 1-phenylpropoxycarbonylamino, 2-phenylpropoxycarbonylamino, 3-phenylpropoxycarbonylamino, 1-naphthylpropoxycarbonylamino, 2-naphthylpropoxycarbonylamino, 3-naphthylpropoxycarbonylamino An amino group substituted with one or two "aralkyloxycarbonyl groups"; preferably an amino group substituted with one or two "aralkyloxycarbonyl groups"; most preferably benzyloxycarbonyl; Group.

In the above formula, specific examples of the “carbamoyl group mono- or di-substituted by a group selected from the group consisting of lower alkyl, aryl and aralkyl” in the definition of the substituent group a include, for example, methylcarbamoyl , Ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, isobutylcarbamoyl, s-butylcarbamoyl, t-butylcarbamoyl, pentylcarbamoyl, isopentylcarbamoyl, 2-methylbutylcarbamoyl, neopentylcarbamoyl, 1-ethylpropylcarbamoyl,
Hexylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl, N-ethylN-methylcarbamoyl,
An amino group in which one or two of the above "lower alkyl groups" are substituted, such as dipropylcarbamoyl, dibutylcarbamoyl, dipentylcarbamoyl, and dihexylcarbamoyl; phenylcarbamoyl, 1-indenylcarbamoyl, 2-indenylcarbamoyl, 1-naphthylcarbamoyl Carbamoyl groups in which one or two of the above “aryl groups” are substituted, such as benzylcarbamoyl, α-naphthylmethylcarbamoyl, β
-Naphthylmethylcarbamoyl, indenylmethylcarbamoyl, diphenylmethylcarbamoyl, triphenylmethylcarbamoyl, 1-phenethylcarbamoyl,
2-phenethylcarbamoyl, 1-naphthylethylcarbamoyl, 2-naphthylethylcarbamoyl, 1-phenylpropylcarbamoyl, 2-phenylpropylcarbamoyl, 3-phenylpropylcarbamoyl, 1-naphthylpropylcarbamoyl, 2-naphthylpropylcarbamoyl, 3-naphthylpropylcarbamoyl A carbamoyl group in which one or two such “aralkyl groups” are substituted; and preferably a methylcarbamoyl, phenylcarbamoyl or benzylcarbamoyl group.

In the above formula, the “halogen atom” in the definition of the substituent group “a” is a fluorine, chlorine, bromine or iodine atom,
Preferably, it is a fluorine atom or a chlorine atom.

In the above formula, the “halogeno lower alkyl group” in the definition of the substituent group “a” is a group in which the above “lower alkyl group” is substituted by a halogen atom. Dichloromethyl, dibromomethyl, fluoromethyl, 2,
2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2-iodoethyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl, , 2
- a dibromoethyl, preferably a C ₁ -C ₄ halogenated lower alkyl group, more preferably a C ₁ -C ₂ halogenated lower alkyl group, most preferably a trifluoromethyl group.

In the above formula, specific examples of “lower alkyl group substituted by 1 to 3 groups selected from substituent group a” in the definition of R ³ , R ^3a and R ⁵ include, for example, methoxymethyl , 1-methoxyethyl, 2-methoxyethyl,
1-methoxypropyl, 2-methoxypropyl, 3-methoxypropyl, ethoxymethyl, 1-ethoxyethyl, 2-ethoxyethyl, 1-propoxyethyl, 2-
Propoxyethyl, t-butoxymethyl, 1- (t-butoxy) ethyl, 2- (t-butoxy) ethyl, 1-
(T-butoxy) propyl, 2- (t-butoxy) propyl, 3- (t-butoxy) propyl, 1-pentyloxyethyl, 2-pentyloxyethyl, 1-phenoxyethyl, 2-phenoxyethyl, 1-benzyl Oxyethyl, 2-benzyloxyethyl, 1-mercaptoethyl, 2-mercaptosiethyl, methylthiomethyl,
-Methylthioethyl, 2-methylthioethyl, 1-methylthiopropyl, 2-methylthiopropyl, 3-methylthiopropyl, ethylthiomethyl, 1-ethylthioethyl, 2-ethylthioethyl, t-butylthiomethyl,
-(T-butylthio) ethyl, 2- (t-butylthio)
Ethyl, 1- (t-butylthio) propyl, 2- (t-
Butylthio) propyl, 3- (t-butylthio) propyl, 1-phenylthioethyl, 2-phenylthioethyl, 1-benzylthioethyl, 2-benzylthioethyl, 1-formylethyl, 2-formylethyl, 1-acetyl Ethyl, 2-acetylethyl, 1-benzoylethyl, 2-benzoylethyl, 1- (benzylcarbonyl) ethyl, 2- (benzylcarbonyl) ethyl, 1-
Carboxyethyl, 2-carboxyethyl, methoxycarbonylmethyl, 1-methoxycarbonylethyl, 2-
Methoxycarbonylethyl, 1-methoxycarbonylpropyl, 2-methoxycarbonylpropyl, 3-methoxycarbonylpropyl, ethoxycarbonylmethyl,
-Ethoxycarbonylethyl, 2-ethoxycarbonylethyl, t-butoxycarbonylmethyl, 1- (t-butoxycarbonyl) ethyl, 2- (t-butoxycarbonyl) ethyl, 1- (t-butoxycarbonyl) propyl, 2- ( t-bumethoxycarbonyl) propyl, 3-
(T-butoxycarbonyl) propyl, 1-phenoxycarbonylethyl, 2-phenoxycarbonylethyl,
Benzyloxycarbonylaminomethyl, 1- (benzyloxycarbonylamino) ethyl, 2- (benzyloxycarbonylamino) ethyl, 3- (benzyloxycarbonylamino) propyl, 4- (benzyloxycarbonylamino) butyl, 5- (benzyl) Oxycarbonylamino) pentyl, 1-aminoethyl, 2-aminoethyl, 1-methylaminoethyl, 2-methylaminoethyl, 1-ethylaminoethyl, 2-ethylaminoethyl, 1-dimethylaminoethyl, 2-dimethylamino Ethyl, 1-diethylaminoethyl, 2-diethylaminoethyl, 1-phenylaminoethyl, 2-phenylaminoethyl, 1-benzylaminoethyl, 2-benzylaminoethyl, 1-carboxyaminoethyl, 2-carboxyaminoethyl 1-methoxycarbonyl-aminoethyl, 2-methoxycarbonyl-aminoethyl, 1-phenoxycarbonyl-aminoethyl, 2-phenoxycarbonyl-aminoethyl, 1-benzyloxycarbonyl-aminoethyl, 2-benzyloxycarbonylamino-ethyl,
1-carbamoylethyl, 2-carbamoylethyl, 1
-Methylcarbamoylethyl, 2-methylcarbamoylethyl, 1-ethylcarbamoylethyl, 2-ethylcarbamoylethyl, 1-dimethylcarbamoylethyl,
2-dimethylcarbamoylethyl, 1-diethylcarbamoylethyl, 2-diethylcarbamoylethyl, 1-
Phenylcarbamoylethyl, 2-phenylcarbamoylethyl, 1-benzylcarbamoylethyl, 2-benzylcarbamoylnoethyl, 1-amidinoethyl, 2-
Amidinoethyl, 1-guanidinoethyl, 2-guanidinoethyl, 1-cyanoethyl, 2-cyanoethyl, the above “halogeno lower alkyl group”, 1-nitroethyl, 2-
Examples thereof include nitroethyl, 1-sulfoethyl and 2-sulfoethyl groups, and preferably a lower alkyl group substituted with lower alkoxy, lower alkylthio, lower alkoxycarbonyl or aralkyloxycarbonylamino.

In the above, the “base addition salt” means that when the compound (I) or (II) of the present invention has a basic group such as an amino group, it is made into a salt by reacting with an acid. Indicate the salt so that it can.

The salt based on a basic group is preferably
Inorganic acid salts such as hydrohalides such as hydrofluoride, hydrochloride, hydrobromide and hydroiodide, nitrates, perchlorates, sulfates and phosphates; methanesulfonic acid Salts, lower alkane sulfonates such as trifluoromethane sulfonate, ethane sulfonate, benzene sulfonate,
aryl sulfonates such as p-toluene sulfonate, acetate, malate, fumarate, succinate,
Organic acid salts such as citrate, ascorbate, tartrate, oxalate, and maleate; and amino acid salts such as glycine, lysine, arginine, ornithine, glutamate, and aspartate. be able to.

In the above, the term "acid addition salt" means that when the compound (I) or (II) of the present invention has an acidic group such as a carboxy group, it can be converted into a salt by reacting it with a base. Show the salt as it can.

The salt based on an acidic group is preferably an alkali metal salt such as a sodium salt, a potassium salt or a lithium salt, an alkaline earth metal salt such as a calcium salt or a magnesium salt, an aluminum salt, an iron salt and the like. Inorganic salts such as ammonium salts, t-octylamine salts, dibenzylamine salts, morpholine salts, glucosamine salts, phenylglycine alkyl ester salts, ethylenediamine salts, N-methylglucamine salts, guanidine salts, diethylamine salts , Triethylamine salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzylphenethylamine salt, piperazine salt,
Amine salts such as organic salts such as tetramethylammonium salt and tris (hydroxymethyl) aminomethane salt; and amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate and aspartate. be able to.

The compound having the general formula (I) or (II) of the present invention absorbs water by leaving it in the air or recrystallizing to absorb water, adhere to water, or form a hydrate. And such hydrates are also included in the salts of the present invention.

The compound having the general formula (I) or (II) of the present invention has various isomers due to the presence of an asymmetric carbon atom in the molecule.

For example, when the dashed line represents a double bond and R ⁶ represents an oxygen atom, the compound having the general formula (I) or (II) has the following general formula (I ′) or (II ′): And the configuration of * 1 may be R-configuration or S-configuration.

[0051]

Embedded image Further, the compound having the general formula (I) or (II) represents a compound having the following general formula (I ″) or (II ″) when the broken line represents a single bond and R ⁶ represents a hydroxy group,
The configurations of * 1 and * 2 are (R, R), (R, S)
It can be a body, (S, R) body or (S, S) body.

[0052]

Embedded image All of these isomers and mixtures of these isomers as described above have a single formula, ie, general formula (I) or (II)
Indicated by Accordingly, the present invention includes all these isomers and mixtures of these isomers in any proportion.

Specific examples of the compound having the general formula (I) or (II) of the present invention include, for example, the compounds shown in Tables 1 to 8 below. However, the present invention is not limited to this. The compounds shown in Tables 1 to 8 correspond to the compounds of the formulas (II-1) to (II-8), respectively.
Having the structural formula

The abbreviations in the table are as follows. Ac: acetyl group Bu: butyl group iBu: isobutyl group tBu: t-butyl group Bz: benzyl group Et: ethyl group Ind (3): indole-3-yl group Me: methyl group Ph: phenyl group Pip (1): Piperidin-1-yl group Pr: propyl group iPr: isopropyl group Pyr (6): pyridin-6-yl group Pyrd (1): pyrrolidin-1-yl group Thi (5): thiophen-5-yl group. [Table 1]

[0055]

Embedded image Compd. R ¹ R ² R ^3a AR ⁵ 1-1 -HH -Me -CONH ₂ H 1-2 -HH -Me -CONHMe H 1-3 -HH -Me -CON (Me) ₂ H 1-4 -HH -Me -CO ₂ HH 1-5- HH -Me -CO ₂ Me H 1-6 -HH -Me -CO ₂ Et H 1-7 -HH -Me -CO ₂ (CH ₂ ) ₂ Br H 1-8 -HH -iBu -CO ₂ Me H 1 -9 -HH -Bz -CO ₂ Me H 1-10 -HH -CH ₂ OtBu -CO ₂ Me H 1-11 -HH -CH ₂ CO ₂ tBu -CO ₂ Me H 1-12 -Me H -Me- CONH ₂ H 1-13 -Me H -Me -CONHMe H 1-14 -Me H -Me -CON (Me) ₂ H 1-15 -Me H -Me -CO ₂ HH 1-16 -Me H -Me- CO ₂ Me H 1-17 -Me H -Me -CO ₂ Et H 1-18 -Me H -Me -CO ₂ (CH ₂ ) ₂ Br H 1-19 -Me H -iBu -CO ₂ Me H 1- 20 -Me H -Bz -CO ₂ Me H 1-21 -Me H -CH ₂ OtBu -CO ₂ Me H 1-22 -Me H -CH ₂ CO ₂ tBu -CO ₂ Me H 1-23 -Ph H- Me -CONH ₂ H 1-24 -Ph H -Me -CONHMe H 1-25 -Ph H -Me -CON (Me) ₂ H 1-26 -Ph H -Me -CO ₂ HH 1-27 -Ph H- Me -CO ₂ Me H 1-28 -Ph H -Me -CO ₂ Et H 1-29 -Ph H -Me -CO ₂ (CH ₂ ) ₂ Br H 1-30 -Ph H -iBu -CO ₂ Me H 1-31 -Ph H -Bz -CO ₂ Me H 1-32 -Ph H -CH ₂ OtBu -CO ₂ Me H 1-33 -Ph H -CH ₂ CO ₂ tBu -CO ₂ Me H 1-34 -Ac H -Me -CONH ₂ H 1-35 -Ac H -Me -CONHMe H 1-36 -Ac H -Me -CON (Me) ₂ H 1-37 -Ac H -Me -CO ₂ HH 1-38 -Ac H -Me -CO ₂ Me H 1-39 -Ac H -Me -CO ₂ Et H 1-40 -Ac H -Me -CO ₂ (CH ₂ ) ₂ Br H 1- 41 -Ac H -iBu -CO ₂ Me H 1-42 -Ac H -Bz -CO ₂ Me H 1-43 -Ac H -CH ₂ OtBu -CO ₂ Me H 1-44 -Ac H -CH ₂ CO ₂ tBu -CO ₂ Me H 1-45 -CO ₂ tBu H -H -CONH ₂ H 1-46 -CO ₂ tBu H -H -CONHMe H 1-47 -CO ₂ tBu H -H -CON (Me) ₂ H 1-48 -CO ₂ tBu H -H -CO ₂ HH 1-49 -CO ₂ tBu H -H -CO ₂ Me H 1-50 -CO ₂ tBu H -H -CO ₂ Et H 1-51 -CO ₂ tBu H -Me -CONH ₂ H 1-52 -CO ₂ tBu H -Me -CONHMe H 1-53 -CO ₂ tBu H -Me -CON (Me) ₂ H 1-54 -CO ₂ tBu H -Me -CONHBu H 1-55 -CO ₂ tBu H -Me -CON (Bu) ₂ H 1-56 -CO ₂ tBu H -Me -CO-Pyrd (1) H 1-57 -CO ₂ tBu H -Me -CONH (2 -CO ₂ Me-Ph) H 1-58 -CO ₂ tBu H -Me -CONH (3-CO ₂ H-Ph) H 1-59 -CO ₂ tBu H -Me -CONH (3-CO ₂ Me-Ph ) H 1-60 -CO ₂ tBu H -Me -CONH (4-CO ₂ H-Ph) H 1-61 -CO ₂ tBu H -Me -CONH (4-CO ₂ Me-Ph) H 1-62- CO ₂ tBu H -Me -CO ₂ HH 1-63 -CO ₂ tBu H -Me -CO ₂ Me H 1-64 -CO ₂ tBu H -Me -CO ₂ Et H 1-65 -CO ₂ tBu H -Me -CO ₂ Bz H 1-66 -CO ₂ tBu H -Me -CO ₂ (CH ₂ ) ₂ Br H 1-67 -CO ₂ tBu H- Me -CO ₂ (CH ₂ ) ₂ Cl H 1-68 -CO ₂ tBu H -Me -CO ₂ H 6-Me 1-69 -CO ₂ tBu H -Me -CO ₂ H 5-Me 6-Me 1- 70 -CO ₂ tBu H -Me -CO ₂ H 6-OMe 5-Me 1-71 -CO ₂ tBu H -Me -CO ₂ Me 6-Me 1-72 -CO ₂ tBu H -Me -CO ₂ Me 6 -Me 5-Me 1-73 -CO ₂ tBu H -Me -CO ₂ Me 6-OMe 5-Me 1-74 -CO ₂ tBu Me -Me -CONHMe H 1-75 -CO ₂ tBu Me -Me -CONHBu H 1-76 -CO ₂ tBu Me -Me -CON (Me) ₂ H 1-77 -CO ₂ tBu Me -Me -CON (Bu) ₂ H 1-78 -CO ₂ tBu Me -Me -CO ₂ HH 1 -79 -CO ₂ tBu Me -Me -CO ₂ Me H 1-80 -CO ₂ tBu H -iPr -CONH ₂ H 1-81 -CO ₂ tBu H -iPr -CONHMe H 1-82 -CO ₂ tBu H- iPr -CON (Me) ₂ H 1-83 -CO ₂ tBu H -iPr -CO ₂ HH 1-84 -CO ₂ tBu H -iPr -CO ₂ Me H 1-85 -CO ₂ tBu H -iPr -CO ₂ Et H 1-86 -CO ₂ tBu H -iBu -CONH ₂ H 1-87 -CO ₂ tBu H -iBu -CONHMe H 1-88 -CO ₂ tBu H -iBu -CON (Me) ₂ H 1-89- CO ₂ tBu H -iBu -CONHBu H 1-90 -CO ₂ tBu H -iBu -CON (Bu) ₂ H 1-91 -CO ₂ tBu H -iBu -CO-Pyrd (1) H 1-92 -CO ₂ tBu H -iBu -CONH (2-CO ₂ Me-Ph) H 1-93 -CO ₂ tBu H -iBu -CONH (3-CO ₂ Me-Ph) H 1-94 -CO ₂ tBu H -iBu -CONH (4-CO ₂ Me-Ph) H 1-95 -CO ₂ tBu H -i _{Bu -CO 2 HH 1-96 -CO 2 tBu} H -iBu -CO 2 Me H 1-97 -CO 2 tBu H -iBu -CO 2 Et H 1-98 -CO 2 tBu H -iBu -CO 2 Bz H 1-99 -CO ₂ tBu H -iBu -CO ₂ (CH ₂ ) ₂ Br H 1-100 -CO ₂ tBu H -iBu -CO ₂ H 6-Me 1-101 -CO ₂ tBu H -iBu -CO ₂ H 6-Me 5-Me 1-102 -CO ₂ tBu H -iBu -CO ₂ H 6-OMe 5-Me 1-103 -CO ₂ tBu H -iBu -CO ₂ Me 6-Me 1-104 -CO ₂ tBu H -iBu -CO ₂ Me 6-Me 5-Me 1-105 -CO ₂ tBu H -iBu -CO ₂ Me 6-OMe 5-Me 1-106 -CO ₂ tBu H -Ph -CONH ₂ H 1- _{107 -CO 2 tBu H -Ph -CONHMe H} 1-108 -CO 2 tBu H -Ph -CON (Me) 2 H 1-109 -CO 2 tBu H -Ph -CO 2 HH 1-110 -CO 2 tBu H -Ph -CO ₂ Me H 1-111 -CO ₂ tBu H -Ph -CO ₂ Et H 1-112 -CO ₂ tBu H -Bz -CONH ₂ H 1-113 -CO ₂ tBu H -Bz -CONHMe H 1 -114 -CO ₂ tBu H -Bz -CON (Me) ₂ H 1-115 -CO ₂ tBu H -Bz -CONHBu H 1-116 -CO ₂ tBu H -Bz -CON (Bu) ₂ H 1-117- CO ₂ tBu H -Bz -CO-Pyrd (1) H 1-118 -CO ₂ tBu H -Bz -CONH (2-CO ₂ Me-Ph) H 1-119 -CO ₂ tBu H -Bz -CONH (3 -CO ₂ Me-Ph) H 1-120 -CO ₂ tBu H -Bz -CONH (4-CO ₂ Me-Ph) H 1-121 -CO ₂ tBu H -Bz -CO ₂ HH 1-122 -CO ₂ tBu H -Bz -CO ₂ Me H 1-123 -CO ₂ tBu H -Bz -CO ₂ Et H 1-124 -CO ₂ tBu H -Bz -CO ₂ Bz H 1-125 -CO ₂ tBu H -Bz -CO ₂ (CH ₂ ) ₂ Br H 1-126 -CO ₂ tBu H -Bz -CO ₂ H 6-Me 1-127 -CO ₂ tBu H -Bz -CO ₂ H 6-Me 5-Me 1-128 -CO ₂ tBu H -Bz -CO ₂ H 6-OMe 5- Me 1-129 -CO ₂ tBu H -Bz -CO ₂ Me 6-Me 1-130 -CO ₂ tBu H -Bz -CO ₂ Me 6-Me 5-Me 1-131 -CO ₂ tBu H -Bz -CO ₂ Me 6-OMe 5-Me 1-132 -CO ₂ tBu H -CH ₂ -Ind (3) -CONH ₂ H 1-133 -CO ₂ tBu H -CH ₂ -Ind (3) -CONHMe H 1-134 -CO ₂ tBu H -CH ₂ -Ind (3) -CON (Me) ₂ H 1-135 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ HH 1-136 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Me H 1-137 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Et H 1-138 -CO ₂ tBu H -CH ₂ OtBu -CONH ₂ H 1- 139 -CO ₂ tBu H -CH ₂ OtBu -CONHMe H 1-140 -CO ₂ tBu H -CH ₂ OtBu -CON (Me) ₂ H 1-141 -CO ₂ tBu H -CH ₂ OtBu -CONHBu H 1-142 -CO ₂ tBu H -CH ₂ OtBu -CON (Bu) ₂ H 1-143 -CO ₂ tBu H -CH ₂ OtBu -CO-Pyrd (1) H 1-144 -CO ₂ tBu H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 1-145 -CO ₂ tBu H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 1-146 -CO ₂ tBu H -CH ₂ OtBu -CONH (4 -CO ₂ Me-Ph) H 1-147 -CO ₂ tB u H -CH ₂ OtBu -CO ₂ HH 1-148 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me H 1-149 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Et H 1-150 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Bz H 1-151 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ (CH ₂ ) ₂ Br H 1-152 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 6 -Me 1-153 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 6-Me 5-154 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 6-OMe 5-Me 1-155- CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 6-Me 1-156 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 6-Me 5-Me 1-157 -CO ₂ tBu H -CH ₂ OtBu- CO ₂ Me 6-OMe 5-Me 1-158 -CO ₂ tBu H -CH (Me) OtBu -CONH ₂ H 1-159 -CO ₂ tBu H -CH (Me) OtBu -CONHMe H 1-160 -CO ₂ tBu H -CH (Me) OtBu -CON (Me) ₂ H 1-161 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ HH 1-162 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Me H 1-163 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Et H 1-164 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CONH ₂ H 1-165 -CO ₂ tBu H-( CH ₂ ) ₂ SMe -CONHMe H 1-166 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 1-167 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ HH 1 -168 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Me H 1-169 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Et H 1-170 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH ₂ H 1-171 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHMe H 1-172 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 1-173 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHBu H 1-174 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 1-175 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO- Pyrd (1) H 1-176 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 1-177 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (3- (CO ₂ Me-Ph) H 1-178 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 1-179 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ HH 1-180 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me H 1-181 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Et H 1-182 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Bz H 1-183 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ (CH ₂ ) ₂ Br H 1-184 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 6-Me 1-185 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 6-Me 5-Me 1-186 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 6-OMe 5- Me 1-187 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 6-Me 1-188 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 6-Me 5-Me 1-189- CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 6-OMe 5-Me 1-190 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 1-191 -CO ₂ t Bu H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 1-192 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 1-193 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 1-194 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 1-195 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 1-196 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 1-197 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 1-198 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 1-199 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 1-200 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 1-201 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 1-202 -CO ₂ tBu H -CH ₂ (4-BzO-Ph ) -CONH ₂ H 1-203 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONHMe H 1-204 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 1-205 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ HH 1-206 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 1-207- CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 1-208 -CO ₂ tBu-(CH ₂ ) ₃ --CONH ₂ H 1-209 -CO ₂ tBu-(CH ₂ ) ₃ --CONHMe H 1-210 -CO ₂ tBu-(CH ₂ ) ₃ --CON (Me) ₂ H 1-211 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ HH 1-212 -CO ₂ tBu -(CH ₂ ) ₃ --CO ₂ Me H 1-213 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ Et H 1-214 -CO ₂ Bz H -H -CONH ₂ H 1-215 -CO ₂ Bz H -H -CONHMe H 1-216- CO ₂ Bz H -H -CON (Me) ₂ H 1-217 -CO ₂ Bz H -H -CO ₂ HH 1-218 -CO ₂ Bz H -H -CO ₂ Me H 1-219 -CO ₂ Bz H -H -CO ₂ Et H 1-220 -CO ₂ Bz H -Me -CONH ₂ H 1-221 -CO ₂ Bz H -Me -CONHMe H 1-222 -CO ₂ Bz H -Me -CON (Me) ₂ H 1-223 -CO ₂ Bz H -Me -CONHBu H 1-224 -CO ₂ Bz H -Me -CON (Bu) ₂ H 1-225 -CO ₂ Bz H -Me -CO-Pyrd (1) H 1 -226 -CO ₂ Bz H -Me -CONH (2-CO ₂ Me-Ph) H 1-227 -CO ₂ Bz H -Me -CONH (3-CO ₂ H-Ph) H 1-228 -CO ₂ Bz H -Me -CONH (3-CO ₂ Me-Ph) H 1-229 -CO ₂ Bz H -Me -CONH (4-CO ₂ H-Ph) H 1-230 -CO ₂ Bz H -Me -CONH ( 4-CO ₂ Me-Ph) H 1-231 -CO ₂ Bz H -Me -CO ₂ HH 1-232 -CO ₂ Bz H -Me -CO ₂ Me H 1-233 -CO ₂ Bz H -Me -CO ₂ Et H 1-234 -CO ₂ Bz H -Me -CO ₂ (CH ₂ ) ₂ Br H 1-235 -CO ₂ Bz H -Me -CO ₂ H 6-Me 1-236 -CO ₂ Bz H -Me -CO ₂ H 6-Me 5-Me 1-237 -CO ₂ Bz H -Me -CO ₂ H 6-OMe 5-Me 1-238 -CO ₂ Bz H -Me -CO ₂ Me 6-Me 1-239 -CO ₂ Bz H -Me -CO ₂ Me 6-Me 5-Me 1-240 -CO ₂ Bz H -Me -CO ₂ Me 6-OMe 5-Me 1 -241 -CO ₂ Bz Me -Me -CONHMe H 1-242 -CO ₂ Bz Me -Me -CONHBu H 1-243 -CO ₂ Bz Me -Me -CON (Me) ₂ H 1-244 -CO ₂ Bz Me -Me -CON (Bu) ₂ H 1-245 -CO ₂ Bz Me -Me -CO ₂ HH 1-246 -CO ₂ Bz Me -Me -CO ₂ Me H 1-247 -CO ₂ Bz H -iPr -CONH ₂ H 1-248 -CO ₂ Bz H -iPr -CONHMe H 1-249 -CO ₂ Bz H -iPr -CON (Me) ₂ H 1-250 -CO ₂ Bz H -iPr -CO ₂ HH 1-251- CO ₂ Bz H -iPr -CO ₂ Me H 1-252 -CO ₂ Bz H -iPr -CO ₂ Et H 1-253 -CO ₂ Bz H -iPr -CO ₂ (CH ₂ ) ₂ Br H 1-254- CO ₂ Bz H -iBu -CONH ₂ H 1-255 -CO ₂ Bz H -iBu -CONHMe H 1-256 -CO ₂ Bz H -iBu -CON (Me) ₂ H 1-257 -CO ₂ Bz H -iBu -CONHBu H 1-258 -CO ₂ Bz H -iBu -CON (Bu) ₂ H 1-259 -CO ₂ Bz H -iBu -CO-Pyrd (1) H 1-260 -CO ₂ Bz H -iBu -CONH (2-CO ₂ Me-Ph) H 1-261 -CO ₂ Bz H -iBu -CONH (3-CO ₂ Me-Ph) H 1-262 -CO ₂ Bz H -iBu -CONH (4-CO ₂ Me -Ph) H 1-263 -CO ₂ Bz H -iBu -CO ₂ HH 1-264 -CO ₂ Bz H -iBu -CO ₂ Me H 1-265 -CO ₂ Bz H -iBu -CO ₂ Et H 1- 266 -CO ₂ Bz H -iBu -CO ₂ Bz H 1-267 -CO ₂ Bz H -iBu -CO ₂ (CH ₂ ) ₂ Br H 1-268 -CO ₂ Bz H -iBu -CO ₂ H 6-Me 1-269 -CO ₂ Bz H -iBu -CO ₂ H 6-Me 5-Me 1-270 -CO ₂ Bz H -iBu -CO ₂ H 6-OMe 5-Me 1-271 -CO ₂ Bz H -iBu -CO ₂ Me 6-Me 1-272 -CO ₂ Bz H -iBu -CO ₂ Me 6-Me 5-Me 1-273 -CO ₂ Bz H -iBu -CO ₂ Me 6-OMe 5-Me 1-274 -CO ₂ Bz H -Ph -CONH ₂ H 1-275 -CO ₂ Bz H -Ph -CONHMe H 1-276 -CO ₂ Bz H -Ph -CON (Me) ₂ H 1-277 -CO ₂ Bz H -Ph -CO ₂ HH 1-278 -CO ₂ Bz H -Ph -CO ₂ Me H 1-279 -CO ₂ Bz H -Ph -CO ₂ Et H 1-280 -CO ₂ Bz H -Ph -CO ₂ (CH ₂ ) ₂ Br H 1-281 -CO ₂ Bz H -Bz -CONH ₂ H 1-282 -CO ₂ Bz H -Bz -CONHMe H 1-283 -CO ₂ Bz H -Bz -CON (Me) ₂ H 1-284 -CO ₂ Bz H -Bz- CONHBu H 1-285 -CO ₂ Bz H -Bz -CON (Bu) ₂ H 1-286 -CO ₂ Bz H -Bz -CO-Pyrd (1) H 1-287 -CO ₂ Bz H -Bz -CONH ( 2-CO ₂ Me-Ph) H 1-288 -CO ₂ Bz H -Bz -CONH (3-CO ₂ Me-Ph) H 1-289 -CO ₂ Bz H -Bz -CONH (4-CO ₂ Me- Ph) H 1-290 -CO ₂ Bz H -Bz -CO ₂ HH 1-291 -CO ₂ Bz H -Bz -CO ₂ Me H 1-292 -CO ₂ Bz H -Bz -CO ₂ Et H 1-293 -CO ₂ Bz H -Bz -CO ₂ HH 1-294 -CO ₂ Bz H -Bz -CO ₂ H 6-Me 1-295 -CO ₂ Bz H -Bz -CO ₂ H 6-Me 5-Me 1- 296 -CO ₂ Bz H -Bz -CO ₂ H 6-OMe 5-Me 1-297 -CO ₂ Bz H -Bz -CO ₂ M e 6-Me 1-298 -CO ₂ Bz H -Bz -CO ₂ Me 6-Me 5-Me 1-299 -CO ₂ Bz H -Bz -CO ₂ Me 6-OMe 5-Me 1-300 -CO ₂ Bz H -Bz -CO ₂ (CH ₂ ) ₂ Br H 1-301 -CO ₂ Bz H -CH ₂ -Ind (3) -CONH ₂ H 1-302 -CO ₂ Bz H -CH ₂ -Ind (3) -CONHMe H 1-303 -CO ₂ Bz H -CH ₂ -Ind (3) -CON (Me) ₂ H 1-304 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ HH 1-305- CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Me H 1-306 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Et H 1-307 -CO ₂ Bz H -CH _2- Ind (3) -CO ₂ (CH ₂ ) ₂ Br H 1-308 -CO ₂ Bz H -CH ₂ OtBu -CONH ₂ H 1-309 -CO ₂ Bz H -CH ₂ OtBu -CONHMe H 1-310 -CO ₂ Bz H -CH ₂ OtBu -CON (Me) ₂ H 1-311 -CO ₂ Bz H -CH ₂ OtBu -CONHBu H 1-312 -CO ₂ Bz H -CH ₂ OtBu -CON (Bu) ₂ H 1- 313 -CO ₂ Bz H -CH ₂ OtBu -CO-Pyrd (1) H 1-314 -CO ₂ Bz H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 1-315 -CO ₂ Bz H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 1-316 -CO ₂ Bz H -CH ₂ OtBu -CONH (4-CO ₂ Me-Ph) H 1-317 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ HH 1-318 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me H 1-319 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Et H 1-320 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Bz H 1-321 -CO ₂ Bz H -CH ₂ OtB u -CO ₂ (CH ₂ ) ₂ Br H 1-322 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 6-Me 1-323 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 6-Me 5 -Me 1-324 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 6-OMe 5-Me 1-325 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 6-Me 1-326 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 6-Me 5-Me 1-327 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 6-OMe 5-Me 1-328 -CO ₂ Bz H -CH (Me) OtBu -CONH ₂ H 1-329 -CO ₂ Bz H -CH (Me) OtBu -CONHMe H 1-330 -CO ₂ Bz H -CH (Me) OtBu -CON (Me) ₂ H 1-331 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ HH 1-332 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Me H 1-333 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Et H 1 -334 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ (CH ₂ ) ₂ Br H 1-335 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONH ₂ H 1-336 -CO ₂ Bz H -(CH ₂ ) ₂ SMe -CONHMe H 1-337 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 1-338 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ HH 1-339 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Me H 1-340 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Et H 1-341 -CO ₂ Bz H- (CH ₂ ) ₂ SMe -CO ₂ (CH ₂ ) ₂ Br H 1-342 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH ₂ H 1-343 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHMe H 1-344 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 1-345 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHBu H 1-346 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 1-347 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 1-348 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 1-349 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 1-350 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 1-351 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ HH 1-352 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me H 1-353 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Et H 1-354 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Bz H 1-355 -CO2B H -CH ₂ CO ₂ tBu -CO ₂ (CH ₂ ) ₂ Br H 1-356 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 6-Me 1-357 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 6-Me 5-Me 1-358 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 6-OMe 5-Me 1-359 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 6-Me 1-360 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 6-Me 5-Me 1-361 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 6-OMe 5-Me 1-362 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu- CONH ₂ H 1-363 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 1-364 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 1-365 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 1-366 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 1-367 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 1-368 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ (CH ₂ ) ₂ Br H 1-369 -CO ₂ Bz H-(CH ₂ ) ₂ NHCO ₂ Bz -CO ₂ Me H 1-370 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 1-371 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 1-372 -CO ₂ Bz H -(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 1-373 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 1-374 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 1-375 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 1-376 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ (CH ₂ ) ₂ Br H 1-377 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONH ₂ H 1-378 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONHMe H 1-379 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 1-380 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ HH 1- 381 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 1-382 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 1-383 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ (CH ₂ ) ₂ Br H 1-384 -CO ₂ Bz-(CH ₂ ) ₃ --CONH ₂ H 1-385 -CO ₂ Bz-(CH ₂ ) ₃ --CONHMe H 1-386 -CO ₂ Bz-(CH ₂ ) _3- -CON (Me) ₂ H 1-387 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ HH 1-388 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ Me H 1-389 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ Et H 1-390 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ (CH ₂ ) ₂ Br H . [Table 2]

[0056]

Embedded image Compd. R ¹ R ² R ^3a AR ⁵ 2-1 -HH -Me -CONH ₂ H 2-2 -HH -Me -CONHMe H 2-3 -HH -Me -CON (Me) ₂ H 2-4 -HH -Me -CONHBu H 2-5 -HH -Me -CON (Bu) ₂ H 2-6 -HH -Me -CO-Pyrd (1) H 2-7 -HH -Me -CO ₂ HH 2-8 -HH -Me -CO ₂ Me H 2-9 -HH -Me -CO ₂ Et H 2-10 -HH -Me -CO ₂ Bz H 2-11 -HH -iBu -CO ₂ HH 2-12 -HH -iBu -CO ₂ Me H 2-13 -HH- Bz -CO ₂ HH 2-14 -HH -Bz -CO ₂ Me H 2-15 -HH -CH ₂ OtBu -CO ₂ HH 2-16 -HH -CH ₂ OtBu -CO ₂ Me H 2-17 -HH- CH ₂ CO ₂ tBu -CO ₂ HH 2-18 -HH -CH ₂ CO ₂ tBu -CO ₂ Me H 2-19 -Me H -Me -CONH ₂ H 2-20 -Me H -Me -CONHMe H 2- 21 -Me H -Me -CON (Me) ₂ H 2-22 -Me H -Me -CONHBu H 2-23 -Me H -Me -CON (Bu) ₂ H 2-24 -Me H -Me -CO- Pyrd (1) H 2-25 -Me H -Me -CO ₂ HH 2-26 -Me H -Me -CO ₂ Me H 2-27 -Me H -Me -CO ₂ Et H 2-28 -Me H- Me -CO ₂ Bz H 2-29 -Me H -iBu -CO ₂ HH 2-30 -Me H -iBu -CO ₂ Me H 2-31 -Me H -Bz -CO ₂ HH 2-32 -Me H- Bz -CO ₂ Me H 2-33 -Me H -CH ₂ OtBu -CO ₂ HH 2-34 -Me H -CH ₂ OtBu -CO ₂ Me H 2-35 -Me H -CH ₂ CO ₂ tBu -CO ₂ HH 2-36 -Me H -CH ₂ CO ₂ tBu -CO ₂ Me H 2-37 -Ph H -Me -CONH ₂ H 2-38 -Ph H -Me -CONH Me H 2-39 -Ph H -Me -CON (Me) ₂ H 2-40 -Ph H -Me -CONHBu H 2-41 -Ph H -Me -CON (Bu) ₂ H 2-42 -Ph H- Me -CO-Pyrd (1) H 2-43 -Ph H -Me -CO ₂ HH 2-44 -Ph H -Me -CO ₂ Me H 2-45 -Ph H -Me -CO ₂ Et H 2-46 -Ph H -Me -CO ₂ Bz H 2-47 -Ph H -iBu -CO ₂ HH 2-48 -Ph H -iBu -CO ₂ Me H 2-49 -Ph H -Bz -CO ₂ HH 2-50 -Ph H -Bz -CO ₂ Me H 2-51 -Ph H -CH ₂ OtBu -CO ₂ HH 2-52 -Ph H -CH ₂ OtBu -CO ₂ Me H 2-53 -Ph H -CH ₂ CO ₂ tBu -CO ₂ HH 2-54 -Ph H -CH ₂ CO ₂ tBu -CO ₂ Me H 2-55 -Ac H -Me -CONH ₂ H 2-56 -Ac H -Me -CONHMe H 2-57 -Ac H -Me -CON (Me) ₂ H 2-58 -Ac H -Me -CONHBu H 2-59 -Ac H -Me -CON (Bu) ₂ H 2-60 -Ac H -Me -CO-Pyrd (1 ) H 2-61 -Ac H -Me -CO ₂ HH 2-62 -Ac H -Me -CO ₂ Me H 2-63 -Ac H -Me -CO ₂ Et H 2-64 -Ac H -Me -CO ₂ Bz H 2-65 -Ac H -iBu -CO ₂ HH 2-66 -Ac H -iBu -CO ₂ Me H 2-67 -Ac H -Bz -CO ₂ HH 2-68 -Ac H -Bz -CO ₂ Me H 2-69 -Ac H -CH ₂ OtBu -CO ₂ HH 2-70 -Ac H -CH ₂ OtBu -CO ₂ Me H 2-71 -Ac H -CH ₂ CO ₂ tBu -CO ₂ HH 2- 72 -Ac H -CH ₂ CO ₂ tBu -CO ₂ Me H 2-73 -CO ₂ tBu H -H -CONH ₂ H 2-74 -CO ₂ tBu _{H -H -CONHMe H 2-75 -CO 2 tBu} H -H -CON (Me) 2 H 2-76 -CO 2 tBu H -H -CONHBu H 2-77 -CO 2 tBu H -H -CON (Bu ) ₂ H 2-78 -CO ₂ tBu H -H -CO-Pyrd (1) H 2-79 -CO ₂ tBu H -H -CO ₂ HH 2-80 -CO ₂ tBu H -H -CO ₂ Me H 2-81 -CO ₂ tBu H -H -CO ₂ Et H 2-82 -CO ₂ tBu H -H -CO ₂ Bz H 2-83 -CO ₂ tBu H -Me -CONH ₂ H 2-84 -CO _{2 tBu H -Me -CONHMe H 2-85 -CO 2} tBu H -Me -CON (Me) 2 H 2-86 -CO 2 tBu H -Me -CONHEt H 2-87 -CO 2 tBu H -Me -CONHBu H 2-88 -CO ₂ tBu H -Me -CON (Bu) ₂ H 2-89 -CO ₂ tBu H -Me -CO-Pyrd (1) H 2-90 -CO ₂ tBu H -Me -CO-Pip ( 1) H 2-91 -CO ₂ tBu H -Me -CONHPh H 2-92 -CO ₂ tBu H -Me -CONH (2-CO ₂ H-Ph) H 2-93 -CO ₂ tBu H -Me -CONH (2-CO ₂ Me-Ph) H 2-94 -CO ₂ tBu H -Me -CONH (2-CO ₂ Et-Ph) H 2-95 -CO ₂ tBu H -Me -CONH (3-CO ₂ H -Ph) H 2-96 -CO ₂ tBu H -Me -CONH (3-CO ₂ Me-Ph) H 2-97 -CO ₂ tBu H -Me -CONH (3-CO ₂ Et-Ph) H 2- 98 -CO ₂ tBu H -Me -CONH (4-CO ₂ H-Ph) H 2-99 -CO ₂ tBu H -Me -CONH (4-CO ₂ Me-Ph) H 2-100 -CO ₂ tBu H -Me -CONH (4-CO ₂ Et-Ph) H 2-101 -CO ₂ tBu H -Me -CONHBz H 2-102 -CO ₂ tBu H -Me -C O ₂ HH 2-103 -CO ₂ tBu H -Me -CO ₂ Me H 2-104 -CO ₂ tBu H -Me -CO ₂ Et H 2-105 -CO ₂ tBu H -Me -CO ₂ Bz H 2- 106 -CO ₂ tBu H -Me -CO2 (2-OH-Bz) H 2-107 -CO ₂ tBu H -Me -CO2 (2-OMe-Bz) H 2-108 -CO ₂ tBu H -Me -CO2 (3-OH-Bz) H 2-109 -CO ₂ tBu H -Me -CO2 (3-OMe-Bz) H 2-110 -CO ₂ tBu H -Me -CO2 (4-OH-Bz) H 2- 111 -CO ₂ tBu H -Me -CO2 (4-OMe-Bz) H 2-112 -CO ₂ tBu H -Me -CO ₂ H 2-OH 2-113 -CO ₂ tBu H -Me -CO ₂ H 2 -Me 2-114 -CO ₂ tBu H -Me -CO ₂ H 2-OMe 2-115 -CO ₂ tBu H -Me -CO ₂ H 5-OH 2-116 -CO ₂ tBu H -Me -CO ₂ H 5-Me 2-117 -CO ₂ tBu H -Me -CO ₂ H 5-OMe 2-118 -CO ₂ tBu H -Me -CO ₂ H 2-Me 5-Me 2-119 -CO ₂ tBu H -Me -CO ₂ H 2-OH 5-Me 2-120 -CO ₂ tBu H -Me -CO ₂ H 2-OMe 5-Me 2-121 -CO ₂ tBu H -Me -CO ₂ Me 2-OH 2-122 -CO ₂ tBu H -Me -CO ₂ Me 2-Me 2-123 -CO ₂ tBu H -Me -CO ₂ Me 2-OMe 2-124 -CO ₂ tBu H -Me -CO ₂ Me 5-OH 2- 125 -CO ₂ tBu H -Me -CO ₂ Me 5-Me 2-126 -CO ₂ tBu H -Me -CO ₂ Me 5-OMe 2-127 -CO ₂ tBu H -Me -CO ₂ Me 2-Me 5 -Me 2-128 -CO ₂ tBu H -Me -CO ₂ Me 2-OH 5-Me 2-129 -CO ₂ tBu H -Me -CO ₂ Me 2-OMe 5-Me 2-130 -CO ₂ tBu Me -Me -CONHMe H 2-131 -CO ₂ tBu Me -Me -CONHBu H 2-132 -CO ₂ tBu Me -Me -CON (Me) ₂ H 2 _{-134 -CO 2 tBu Me -Me -CON (} Bu) 2 H 2-135 -CO 2 tBu Me -Me -CO-Pyrd (1) H 2-136 -CO 2 tBu Me -Me -CONH (2-CO ₂ Me-Ph) H 2-137 -CO ₂ tBu Me -Me -CONH (3-CO ₂ Et-Ph) H 2-138 -CO ₂ tBu Me -Me -CONH (4-CO ₂ Me-Ph) H _{2-139 -CO 2 tBu Me -Me -CO 2} HH 2-140 -CO 2 tBu Me -Me -CO 2 Me H 2-141 -CO 2 tBu Me -Me -CO 2 Bz H 2-142 -CO 2 tBu Me -Me -CO2 (4-OMe-Bz) H 2-143 -CO ₂ tBu H -Et -CO ₂ Me H 2-144 -CO ₂ tBu H -Pr -CO ₂ Me H 2-145 -CO _{2 tBu H -iPr -CONH 2 H 2-146 -CO} 2 tBu H -iPr -CONHMe H 2-147 -CO 2 tBu H -iPr -CON (Me) 2 H 2-148 -CO 2 tBu H -iPr -CONHBu H 2-149 -CO ₂ tBu H -iPr -CON (Bu) ₂ H 2-150 -CO ₂ tBu H -iPr -CO-Pyrd (1) H 2-151 -CO ₂ tBu H -iPr -CO ₂ HH 2-152 -CO ₂ tBu H -iPr -CO ₂ Me H 2-153 -CO ₂ tBu H -iPr -CO ₂ Et H 2-154 -CO ₂ tBu H -iPr -CO2 (4-MeO-Bz) H 2-155 -CO ₂ tBu H -Bu -CO ₂ Me H 2-156 -CO ₂ tBu H -iBu -CONH ₂ H 2-157 -CO ₂ tBu H -iBu -CONHMe H 2-158 -CO ₂ tBu H -iBu -C ON (Me) ₂ H 2-159 -CO ₂ tBu H -iBu -CONHBu H 2-160 -CO ₂ tBu H -iBu -CON (Bu) ₂ H 2-161 -CO ₂ tBu H -iBu -CO-Pyrd (1) H 2-162 -CO ₂ tBu H -iBu -CONH (2-CO ₂ Me-Ph) H 2-163 -CO ₂ tBu H -iBu -CONH (3-CO ₂ H-Ph) H 2- 164 -CO ₂ tBu H -iBu -CONH (3-CO ₂ Me-Ph) H 2-165 -CO ₂ tBu H -iBu -CONH (4-CO ₂ H-Ph) H 2-166 -CO ₂ tBu H -iBu -CONH (4-CO ₂ Me-Ph) H 2-167 -CO ₂ tBu H -iBu -CO ₂ HH 2-168 -CO ₂ tBu H -iBu -CO ₂ Me H 2-169 -CO ₂ tBu H -iBu -CO ₂ Et H 2-170 -CO ₂ tBu H -iBu -CO ₂ Bz H 2-171 -CO ₂ tBu H -iBu -CO ₂ H 2-Me 2-172 -CO ₂ tBu H -iBu -CO ₂ H 2-Me 5-Me 2-173 -CO ₂ tBu H -iBu -CO ₂ H 2-OMe 5-Me 2-174 -CO ₂ tBu H -iBu -CO ₂ Me 2-Me 2-175 -CO ₂ tBu H -iBu -CO ₂ Me 2-Me 5-Me 2-176 -CO ₂ tBu H -iBu -CO ₂ Me 2-OMe 5-Me 2-177 -CO ₂ tBu Me -iBu -CONHMe H 2-178 -CO ₂ tBu Me -iBu -CONHBu H 2-179 -CO ₂ tBu Me -iBu -CON (Me) ₂ H 2-180 -CO ₂ tBu Me -iBu -CON (Bu) ₂ H 2-181 -CO ₂ tBu Me -iBu -CO ₂ HH 2-182 -CO ₂ tBu Me -iBu -CO ₂ Me H 2-183 -CO ₂ tBu H -Ph -CONH ₂ H 2-184 -CO ₂ tBu H -Ph -CONHMe H 2-185 -CO ₂ tBu H -Ph -CON (Me) ₂ H 2-186 -CO ₂ tBu H -Ph -CONHBu H 2-187 -CO ₂ tBu H -Ph -CON (Bu) ₂ H 2-188 -CO ₂ tBu H- Ph -CO-Pyrd (1) H 2-189 -CO ₂ tBu H -Ph -CO ₂ HH 2-190 -CO ₂ tBu H -Ph -CO ₂ Me H 2-191 -CO ₂ tBu H -Ph -CO ₂ Et H 2-192 -CO ₂ tBu H -Ph -CO ₂ Bz H 2-193 -CO ₂ tBu H -Bz -CONH ₂ H 2-194 -CO ₂ tBu H -Bz -CONHMe H 2-195 -CO ₂ tBu H -Bz -CON (Me) ₂ H 2-196 -CO ₂ tBu H -Bz -CONHBu H 2-197 -CO ₂ tBu H -Bz -CON (Bu) ₂ H 2-198 -CO ₂ tBu H -Bz -CO-Pyrd (1) H 2-199 -CO ₂ tBu H -Bz -CONH (2-CO ₂ Me-Ph) H 2-200 -CO ₂ tBu H -Bz -CONH (3-CO ₂ H -Ph) H 2-201 -CO ₂ tBu H -Bz -CONH (3-CO ₂ Me-Ph) H 2-202 -CO ₂ tBu H -Bz -CONH (4-CO ₂ H-Ph) H 2- 203 -CO ₂ tBu H -Bz -CONH (4-CO ₂ Me-Ph) H 2-204 -CO ₂ tBu H -Bz -CO ₂ HH 2-205 -CO ₂ tBu H -Bz -CO ₂ Me H 2 -206 -CO ₂ tBu H -Bz -CO ₂ Et H 2-207 -CO ₂ tBu H -Bz -CO ₂ Bz H 2-208 -CO ₂ tBu H -Bz -CO ₂ H 2-Me 2-209- CO ₂ tBu H -Bz -CO ₂ H 2-Me 5-Me 2-210 -CO ₂ tBu H -Bz -CO ₂ H 2-OMe 5-Me 2-211 -CO ₂ tBu H -Bz -CO ₂ Me 2-Me 2-212 -CO ₂ tBu H -Bz -CO ₂ Me 2-Me 5-Me 2-213 -CO ₂ tBu H -Bz -CO ₂ Me 2-OMe 5-Me 2-214 -CO ₂ tBu Me -Bz -CONHMe H 2-215 -CO ₂ tBu Me -Bz -CONHBu H 2-216- CO ₂ tBu Me -Bz -CON (Me) ₂ H 2-217 -CO ₂ tBu Me -Bz -CON (Bu) ₂ H 2-218 -CO ₂ tBu Me -Bz -CO ₂ HH 2-219 -CO ₂ tBu Me -Bz -CO ₂ Me H 2-220 -CO ₂ tBu H -CH ₂ -Ind (3) -CONH ₂ H 2-221 -CO ₂ tBu H -CH ₂ -Ind (3) -CONHMe H 2- 222 -CO ₂ tBu H -CH ₂ -Ind (3) -CON (Me) ₂ H 2-223 -CO ₂ tBu H -CH ₂ -Ind (3) -CONHBu H 2-224 -CO ₂ tBu H -CH ₂ -Ind (3) -CON (Bu) ₂ H 2-225 -CO ₂ tBu H -CH ₂ -Ind (3) -CO-Pyrd (1) H 2-226 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ HH 2-227 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Me H 2-228 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Et H 2 -229 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Bz H 2-230 -CO ₂ tBu H -CH ₂ OH -CO ₂ Me H 2-231 -CO ₂ tBu H -CH ₂ OMe- CO ₂ Me H 2-232 -CO ₂ tBu H -CH ₂ OtBu -CONH ₂ H 2-233 -CO ₂ tBu H -CH ₂ OtBu -CONHMe H 2-234 -CO ₂ tBu H -CH ₂ OtBu -CON ( Me) ₂ H 2-235 -CO ₂ tBu H -CH ₂ OtBu -CONHBu H 2-236 -CO ₂ tBu H -CH ₂ OtBu -CON (Bu) ₂ H 2-237 -CO ₂ tBu H -CH ₂ OtBu -CO-Pyrd (1) H 2 -238 -CO ₂ tBu H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 2-239 -CO ₂ tBu H -CH ₂ OtBu -CONH (3-CO ₂ H-Ph) H 2-240 -CO ₂ tBu H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 2-241 -CO ₂ tBu H -CH ₂ OtBu -CONH (4-CO ₂ H-Ph) H 2-242 -CO ₂ tBu H -CH ₂ OtBu -CONH (4-CO ₂ Me-Ph) H 2-243 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ HH 2-244 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me H 2-245 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Et H 2-246 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Bz H 2-247 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-Me 2-248 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-Me 5-Me 2-249 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-OMe 5-Me 2 -250 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-Me 2-251 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-Me 5-Me 2-252 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-OMe 5-Me 2-253 -CO ₂ tBu Me -CH ₂ OtBu -CONHMe H 2-254 -CO ₂ tBu Me -CH ₂ OtBu -CONHBu H 2-255 -CO ₂ tBu Me -CH ₂ OtBu -CON (Me) ₂ H 2-256 -CO ₂ tBu Me -CH ₂ OtBu -CON (Bu) ₂ H 2-257 -CO ₂ tBu Me -CH ₂ OtBu -CO ₂ HH 2-258- CO ₂ tBu Me -CH ₂ OtBu -CO ₂ Me H 2-259 -CO ₂ tBu H -CH (Me) OH -CO ₂ Me H 2-260 -CO ₂ tBu H -CH (Me) OtB u -CONH ₂ H 2-261 -CO ₂ tBu H -CH (Me) OtBu -CONHMe H 2-262 -CO ₂ tBu H -CH (Me) OtBu -CON (Me) ₂ H 2-263 -CO ₂ tBu H -CH (Me) OtBu -CONHBu H 2-264 -CO ₂ tBu H -CH (Me) OtBu -CON (Bu) ₂ H 2-265 -CO ₂ tBu H -CH (Me) OtBu -CO-Pyrd ( 1) H 2-266 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ HH 2-267 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Me H 2-268 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Et H 2-269 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Bz H 2-270 -CO ₂ tBu H -CH ₂ SMe -CO ₂ Me H 2-271 -CO _{2 tBu H - (CH 2)} 2 SMe -CONH 2 H 2-272 -CO 2 tBu H - (CH 2) 2 SMe -CONHMe H 2-273 -CO 2 tBu H - (CH 2) 2 SMe -CON ( _{Me) 2 H 2-274 -CO 2 tBu} H - (CH 2) 2 SMe -CONHBu H 2-275 -CO 2 tBu H - (CH 2) 2 SMe -CON (Bu) 2 H 2-276 -CO 2 tBu H-(CH ₂ ) ₂ SMe -CO-Pyrd (1) H 2-277 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ HH 2-278 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Me H 2-279 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Et H 2-280 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Bz H 2-281- CO ₂ tBu H -CH ₂ CO ₂ H -CO ₂ Me H 2-282 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ H -CO ₂ Me H 2-283 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH ₂ H 2-2 84 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHMe H 2-285 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 2-286 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHBu H 2-287 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 2-288 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 2-289- CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 2-290 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ H-Ph) H 2- 291 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 2-292 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ H-Ph) H 2-293 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 2-294 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ HH 2-295 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me H 2-296 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Et H 2-297 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Bz H 2-298 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 2-299 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-Me 2-300- CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-OMe 5-Me 2-301 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 2-302 -CO ₂ tBu H- CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 5-Me 2-303 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-OMe 5-Me 2-304 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CONHMe H 2-305 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CONHBu H 2-306 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CON (Me) ₂ H 2-307 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 2-308 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CO ₂ HH 2-309 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CO ₂ Me H 2-310 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 2-311 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 2-312 -CO ₂ tBu H- (CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 2-313 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CONHBu H 2-314 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CON (Bu) ₂ H 2-315 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO-Pyrd (1) H 2-316 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 2-317 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 2-318 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 2 -319 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Bz H 2-320 -CO ₂ tBu H -CH ₂ NH ₂ -CO ₂ Me H 2-321 -CO ₂ tBu H-(CH ₂ ) ₂ NH ₂ -CO ₂ Me H 2-322 -CO ₂ tBu H -CH ₂ NHCO ₂ tBu -CO ₂ Me H 2-323 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ tBu -CO ₂ Me H 2-324 -CO ₂ tBu H-(CH ₂ ) ₂ NHCO ₂ Bz -CO ₂ Me H 2-325 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO _{2 Bz -CONH 2 H 2-326 -CO 2 tBu} H - (CH 2) 4 NHCO 2 Bz -CONHMe H 2-327 -CO 2 tBu H - (CH 2) 4 NHCO 2 Bz -CON (Me) 2 H 2 _{-328 -CO 2 tBu H - (CH} 2) 4 NHCO 2 Bz -CONHBu H 2-329 -CO 2 tBu H - (CH 2) 4 NHCO 2 Bz -CON (Bu) 2 H 2-330 -CO 2 tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO-Pyrd (1) H 2-331 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 2-332 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 2-333 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 2-334 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Bz H 2-335 -CO ₂ tBu H -CH ₂ (4-OH-Ph) -CO ₂ Me H 2-336 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONH ₂ H 2-337 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONHMe H 2-338 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 2-339- CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONHBu H 2-340 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CON (Bu) ₂ H 2-341 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO-Pyrd (1) H 2-342 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ HH 2-343 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 2-344 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 2-345 -CO ₂ tBu H -CH ₂ (4- BzO-Ph) -CO ₂ Bz H 2-346 -CO ₂ Bz H -H -CONH ₂ H 2-347 -CO ₂ Bz H -H -CONHMe H 2-348 -CO ₂ Bz H -H -CON (Me) ₂ H 2-349 -CO ₂ Bz H -H -CONHBu H 2-350 -CO ₂ Bz H -H -CON (Bu) ₂ H 2-351 -CO ₂ Bz H -H -CO-Pyrd (1) H 2-352 -CO ₂ Bz H -H -CO ₂ HH 2-353 -CO ₂ Bz H -H -CO ₂ Me H 2-354 -CO ₂ Bz H -H -CO ₂ Et H 2-355 -CO ₂ Bz H -H -CO ₂ Bz H 2-356 -CO ₂ Bz H -Me -CONH ₂ H 2-357 -CO ₂ Bz H -Me -CONHMe H 2-358 -CO ₂ Bz H -Me -CON (Me) ₂ H 2-359 -CO ₂ Bz H -Me -CONHEt H 2-360 -CO ₂ Bz H -Me -CONHBu H 2-361 -CO ₂ Bz H -Me -CON (Bu) ₂ H 2-362 -CO ₂ Bz H -Me -CO-Pyrd (1) H 2-363 -CO ₂ Bz H -Me -CO-Pip (1) H 2-364 -CO ₂ Bz H -Me -CONHPh H 2-365 -CO ₂ Bz H -Me -CONH (2-CO ₂ H-Ph) H 2-366- CO ₂ Bz H -Me -CONH (2-CO ₂ Me-Ph) H 2-367 -CO ₂ Bz H -Me -CONH (2-CO ₂ Et-Ph) H 2-368 -CO ₂ Bz H -Me -CONH (3-CO ₂ H-Ph) H 2-369 -CO ₂ Bz H -Me -CONH (3-CO ₂ Me-Ph) H 2-370 -CO ₂ Bz H -Me -CONH (3-CO ₂ Et-Ph) H 2-371 -CO ₂ Bz H -Me -CONH (4-CO ₂ H-Ph) H 2-372 -CO ₂ Bz H -Me -CONH (4-CO ₂ Me-Ph) H 2-373 -CO ₂ Bz H -Me -CONH (4-CO ₂ Et-Ph) H 2-374 -CO ₂ Bz H -Me -CONHBz H 2-375 -C O ₂ Bz H -Me -CO ₂ HH 2-376 -CO ₂ Bz H -Me -CO ₂ Me H 2-377 -CO ₂ Bz H -Me -CO ₂ Et H 2-378 -CO ₂ Bz H -Me -CO ₂ Bz H 2-379 -CO ₂ Bz H -Me -CO2 (2-OH-Bz) H 2-380 -CO ₂ Bz H -Me -CO2 (2-OMe-Bz) H 2-381 -CO ₂ Bz H -Me -CO2 (3-OH-Bz) H 2-382 -CO ₂ Bz H -Me -CO2 (3-OMe-Bz) H 2-383 -CO ₂ Bz H -Me -CO2 (4- OH-Bz) H 2-384 -CO ₂ Bz H -Me -CO2 (4-OMe-Bz) H 2-385 -CO ₂ Bz H -Me -CO ₂ H 2-OH 2-386 -CO ₂ Bz H -Me -CO ₂ H 2-Me 2-387 -CO ₂ Bz H -Me -CO ₂ H 2-OMe 2-388 -CO ₂ Bz H -Me -CO ₂ H 5-OH 2-389 -CO ₂ Bz H -Me -CO ₂ H 5-Me 2-390 -CO ₂ Bz H -Me -CO ₂ H 5-OMe 2-391 -CO ₂ Bz H -Me -CO ₂ H 2-Me 5-Me 2-392 -CO ₂ Bz H -Me -CO ₂ H 2-OH 5-Me 2-393 -CO ₂ Bz H -Me -CO ₂ H 2-OMe 5-Me 2-394 -CO ₂ Bz H -Me -CO ₂ Me 2-OH 2-395 -CO ₂ Bz H -Me -CO ₂ Me 2-Me 2-396 -CO ₂ Bz H -Me -CO ₂ Me 2-OMe 2-397 -CO ₂ Bz H -Me -CO ₂ Me 5-OH 2-398 -CO ₂ Bz H -Me -CO ₂ Me 5-Me 2-399 -CO ₂ Bz H -Me -CO ₂ Me 5-OMe 2-400 -CO ₂ Bz H -Me- CO ₂ Me 2-Me 5-Me 2-401 -CO ₂ Bz H -Me -CO ₂ Me 2-OH 5-Me 2-402 -CO ₂ Bz H -Me -CO ₂ Me 2-OMe 5-Me 2-403 -CO ₂ Bz Me -Me -CONHMe H 2-404 -CO ₂ Bz Me -Me -CONHBu H 2-405 -CO ₂ Bz Me -Me -CON (Me) ₂ H 2-406 -CO ₂ Bz Me -Me -CON (Bu) ₂ H 2-407 -CO ₂ Bz Me -Me -CO-Pyrd (1) H 2-408 -CO ₂ Bz Me -Me -CONH (2-CO ₂ Me-Ph) H 2-409 -CO ₂ Bz Me -Me -CONH (3-CO ₂ Et-Ph) H 2-410 -CO ₂ Bz Me -Me -CONH (4-CO ₂ Me-Ph) H 2-411 -CO ₂ Bz Me -Me -CO ₂ HH 2-412 -CO ₂ Bz Me -Me -CO ₂ Me H 2-413 -CO ₂ Bz Me -Me -CO ₂ Bz H 2-414 -CO ₂ Bz Me -Me -CO2 (4-OMe-Bz) H 2-415 -CO ₂ Bz H -Et -CO ₂ Me H 2-416 -CO ₂ Bz H -Pr -CO ₂ Me H 2-417 -CO ₂ Bz H -iPr -CONH ₂ H 2-418 -CO ₂ Bz H -iPr -CONHMe H 2-419 -CO ₂ Bz H -iPr -CON (Me) ₂ H 2-420 -CO ₂ Bz H -iPr -CONHBu H 2-421 -CO ₂ Bz H -iPr -CON (Bu) ₂ H 2-422 -CO ₂ Bz H -iPr -CO-Pyrd (1) H 2-423 -CO ₂ Bz H -iPr -CO ₂ HH 2-424 -CO ₂ Bz H -iPr -CO ₂ Me H 2-425 -CO ₂ Bz H -iPr -CO ₂ Et H 2-426 -CO ₂ Bz H -iPr -CO ₂ Bz H 2-427 -CO ₂ Bz H -Bu- CO ₂ Me H 2-428 -CO ₂ Bz H -iBu -CONH ₂ H 2-429 -CO ₂ Bz H -iBu -CONHMe H 2-430 -CO ₂ Bz H -iBu -CON (Me) ₂ H 2- 431 -CO ₂ Bz H -iBu -CONHBu H 2-4 32 -CO ₂ Bz H -iBu -CON (Bu) ₂ H 2-433 -CO ₂ Bz H -iBu -CO-Pyrd (1) H 2-434 -CO ₂ Bz H -iBu -CONH (2-CO ₂ Me-Ph) H 2-435 -CO ₂ Bz H -iBu -CONH (3-CO ₂ H-Ph) H 2-436 -CO ₂ Bz H -iBu -CONH (3-CO ₂ Me-Ph) H 2 -437 -CO ₂ Bz H -iBu -CONH (4-CO ₂ H-Ph) H 2-438 -CO ₂ Bz H -iBu -CONH (4-CO ₂ Me-Ph) H 2-439 -CO ₂ Bz H -iBu -CO ₂ HH 2-440 -CO ₂ Bz H -iBu -CO ₂ Me H 2-441 -CO ₂ Bz H -iBu -CO ₂ Et H 2-442 -CO ₂ Bz H -iBu -CO ₂ Bz H 2-443 -CO ₂ Bz H -iBu -CO ₂ H 2-Me 2-444 -CO ₂ Bz H -iBu -CO ₂ H 2-Me 5-Me 2-445 -CO ₂ Bz H -iBu- CO ₂ H 2-OMe 5-Me 2-446 -CO ₂ Bz H -iBu -CO ₂ Me 2-Me 2-447 -CO ₂ Bz H -iBu -CO ₂ Me 2-Me 5-Me 2-448- CO ₂ Bz H -iBu -CO ₂ Me 2-OMe 5-Me 2-449 -CO ₂ Bz Me -iBu -CONHMe H 2-450 -CO ₂ Bz Me -iBu -CONHBu H 2-451 -CO ₂ Bz Me -iBu -CON (Me) ₂ H 2-452 -CO ₂ Bz Me -iBu -CON (Bu) ₂ H 2-453 -CO ₂ Bz Me -iBu -CO ₂ HH 2-454 -CO ₂ Bz Me -iBu -CO ₂ Me H 2-455 -CO ₂ Bz H -Ph -CONH ₂ H 2-456 -CO ₂ Bz H -Ph -CONHMe H 2-457 -CO ₂ Bz H -Ph -CON (Me) ₂ H 2 -458 -CO ₂ Bz H -Ph -CONHBu H 2-459 -CO ₂ Bz H- Ph -CON (Bu) ₂ H 2-460 -CO ₂ Bz H -Ph -CO-Pyrd (1) H 2-461 -CO ₂ Bz H -Ph -CO ₂ HH 2-462 -CO ₂ Bz H -Ph -CO ₂ Me H 2-463 -CO ₂ Bz H -Ph -CO ₂ Et H 2-464 -CO ₂ Bz H -Ph -CO ₂ Bz H 2-465 -CO ₂ Bz H -Bz -CONH ₂ H 2 -466 -CO ₂ Bz H -Bz -CONHMe H 2-467 -CO ₂ Bz H -Bz -CON (Me) ₂ H 2-468 -CO ₂ Bz H -Bz -CONHBu H 2-469 -CO ₂ Bz H -Bz -CON (Bu) ₂ H 2-470 -CO ₂ Bz H -Bz -CO-Pyrd (1) H 2-471 -CO ₂ Bz H -Bz -CONH (2-CO ₂ Me-Ph) H 2 -472 -CO ₂ Bz H -Bz -CONH (3-CO ₂ H-Ph) H 2-473 -CO ₂ Bz H -Bz -CONH (3-CO ₂ Me-Ph) H 2-474 -CO ₂ Bz H -Bz -CONH (4-CO ₂ H-Ph) H 2-475 -CO ₂ Bz H -Bz -CONH (4-CO ₂ Me-Ph) H 2-476 -CO ₂ Bz H -Bz -CO ₂ HH 2-477 -CO ₂ Bz H -Bz -CO ₂ Me H 2-478 -CO ₂ Bz H -Bz -CO ₂ Et H 2-479 -CO ₂ Bz H -Bz -CO ₂ Bz H 2-480- CO ₂ Bz H -Bz -CO ₂ H 2-Me 2-481 -CO ₂ Bz H -Bz -CO ₂ H 2-Me 5-Me 2-482 -CO ₂ Bz H -Bz -CO ₂ H 2-OMe 5-Me 2-483 -CO ₂ Bz H -Bz -CO ₂ Me 2-Me 2-484 -CO ₂ Bz H -Bz -CO ₂ Me 2-Me 5-Me 2-485 -CO ₂ Bz H -Bz -CO ₂ Me 2-OMe 5-Me 2-486 -CO ₂ Bz Me -Bz -CONHMe H 2-487 -CO ₂ Bz Me -Bz -CONH Bu H 2-488 -CO ₂ Bz Me -Bz -CON (Me) ₂ H 2-489 -CO ₂ Bz Me -Bz -CON (Bu) ₂ H 2-490 -CO ₂ Bz Me -Bz -CO ₂ HH 2-491 -CO ₂ Bz Me -Bz -CO ₂ Me H 2-492 -CO ₂ Bz H -CH ₂ -Ind (3) -CONH ₂ H 2-493 -CO ₂ Bz H -CH ₂ -Ind (3 ) -CONHMe H 2-494 -CO ₂ Bz H -CH ₂ -Ind (3) -CON (Me) ₂ H 2-495 -CO ₂ Bz H -CH ₂ -Ind (3) -CONHBu H 2-496- CO ₂ Bz H -CH ₂ -Ind (3) -CON (Bu) ₂ H 2-497 -CO ₂ Bz H -CH ₂ -Ind (3) -CO-Pyrd (1) H 2-498 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ HH 2-499 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Me H 2-500 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Et H 2-501 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Bz H 2-502 -CO ₂ Bz H -CH ₂ OH -CO ₂ Me H 2-503 -CO ₂ Bz H -CH ₂ OMe -CO ₂ Me H 2-504 -CO ₂ Bz H -CH ₂ OtBu -CONH ₂ H 2-505 -CO ₂ Bz H -CH ₂ OtBu -CONHMe H 2-506 -CO ₂ Bz H- CH ₂ OtBu -CON (Me) ₂ H 2-507 -CO ₂ Bz H -CH ₂ OtBu -CONHBu H 2-508 -CO ₂ Bz H -CH ₂ OtBu -CON (Bu) ₂ H 2-509 -CO ₂ Bz H -CH ₂ OtBu -CO-Pyrd (1) H 2-510 -CO ₂ Bz H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 2-511 -CO ₂ Bz H -CH ₂ OtBu -CONH (3-CO ₂ H-Ph) H 2-512 -CO ₂ Bz H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 2-513 -CO ₂ Bz H -CH ₂ OtBu -CONH (4-CO ₂ H-Ph) H 2-514 -CO ₂ Bz H -CH ₂ OtBu -CONH (4-CO ₂ Me-Ph) H 2-515 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ HH 2-516 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me H 2-517 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Et H 2-518 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Bz H 2-519 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-Me 2-520- CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-Me 5-Me 2-521 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-OMe 5-Me 2-522 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-Me 2-523 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-Me 5-Me 2-524 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-OMe 5-Me 2-525 -CO ₂ Bz Me -CH ₂ OtBu -CONHMe H 2-526 -CO ₂ Bz Me -CH ₂ OtBu -CONHBu H 2-527 -CO ₂ Bz Me -CH ₂ OtBu -CON (Me) ₂ H 2-528 -CO ₂ Bz Me -CH ₂ OtBu -CON (Bu) ₂ H 2-529 -CO ₂ Bz Me -CH ₂ OtBu -CO ₂ HH 2-530 -CO ₂ Bz Me -CH ₂ OtBu- CO ₂ Me H 2-531 -CO ₂ Bz H -CH (Me) OH -CO ₂ Me H 2-532 -CO ₂ Bz H -CH (Me) OtBu -CONH ₂ H 2-533 -CO ₂ Bz H- CH (Me) OtBu -CONHMe H 2-534 -CO ₂ Bz H -CH (Me) OtBu -CON (Me) ₂ H 2-535 -CO ₂ Bz H -CH (Me) OtBu -CONHBu H 2-536- CO ₂ Bz H -CH (Me) OtBu -CON (Bu) ₂ H 2-537 -CO ₂ Bz H -CH (Me) OtBu -CO-Pyrd (1) H 2-538 -CO ₂ Bz H -CH (Me) OtBu- CO ₂ HH 2-539 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Me H 2-540 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Et H 2-541 -CO ₂ Bz H- CH (Me) OtBu -CO ₂ Bz H 2-542 -CO ₂ Bz H -CH ₂ SMe -CO ₂ Me H 2-543 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONH ₂ H 2-544- CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONHMe H 2-545 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 2-546 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONHBu H 2-547 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CON (Bu) ₂ H 2-548 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO-Pyrd (1) H 2 -549 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ HH 2-550 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Me H 2-551 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Et H 2-552 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Bz H 2-553 -CO ₂ Bz H -CH ₂ CO ₂ H -CO ₂ Me H 2-554 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ H -CO ₂ Me H 2-555 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH ₂ H 2-556 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHMe H 2-557 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 2-558 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHBu H 2-559 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 2-560 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 2-561 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 2- 562 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ H-Ph) H 2-563 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 2-564 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ H-Ph) H 2-565 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph ) H 2-566 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ HH 2-567 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me H 2-568 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Et H 2-569 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Bz H 2-570 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 2- 571 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-Me 2-572 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-OMe 5-Me 2-573- CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 2-574 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 5-Me 2-575 -CO ₂ Bz H- CH ₂ CO ₂ tBu -CO ₂ Me 2-OMe 5-Me 2-576 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CONHMe H 2-577 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CONHBu H 2 -578 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CON (Me) ₂ H 2-579 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 2-580 -CO ₂ Bz Me- CH ₂ CO ₂ tBu -CO ₂ HH 2 -581 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CO ₂ Me H 2-582 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 2-583 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 2-584 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 2-585 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONHBu H 2-586 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CON (Bu) ₂ H 2-587 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO-Pyrd (1 ) H 2-588 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 2-589 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 2-590 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 2-591 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Bz H 2-592 -CO ₂ Bz H -CH ₂ NH ₂ -CO ₂ Me H 2-593 -CO ₂ Bz H-(CH ₂ ) ₂ NH ₂ -CO ₂ Me H 2-594 -CO ₂ Bz H -CH ₂ NHCO ₂ tBu -CO ₂ Me H 2-595 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ tBu -CO ₂ Me H 2-596 -CO ₂ Bz H-(CH ₂ ) ₂ NHCO ₂ Bz -CO ₂ Me H 2-597 -CO ₂ Bz H- (CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 2-598 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 2-599 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz- _{CON (Me) 2 H 2-600 -CO} 2 Bz H - (CH 2) 4 NHCO 2 Bz -CONHBu H 2-601 -CO 2 Bz H - (CH 2) 4 NHCO 2 Bz -CON (Bu) 2 H 2- 602 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO-Pyrd (1) H 2-603 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 2-604 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 2-605 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 2-606 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Bz H 2-607 -CO ₂ Bz H -CH ₂ (4-OH-Ph) -CO ₂ Me H 2-608 -CO ₂ Bz H -CH ₂ (4-BzO-Ph ) -CONH ₂ H 2-609 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONHMe H 2-610 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 2-611 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONHBu H 2-612 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CON (Bu) ₂ H 2-613 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO-Pyrd (1) H 2-614 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ HH 2-615 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 2-616 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 2-617 -CO ₂ Bz H- CH ₂ (4-BzO-Ph) -CO ₂ Bz H 2-618 -CO ₂ tBu-(CH ₂ ) ₃ --CONH ₂ H 2-619 -CO ₂ tBu-(CH ₂ ) ₃ --CONHMe H 2 _{-620 -CO 2 tBu - (CH 2} ) 3 - -CON (Me) 2 H 2-621 -CO 2 tBu - (CH 2) 3 - -CO 2 HH 2-622 -CO 2 tBu - (CH 2) ₃ --CO ₂ Me H 2-623 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ Et H 2-624 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ (CH ₂ ) ₂ Br H 2-625 -CO ₂ Bz-(CH ₂ ) ₃ --CONH ₂ H 2-626 -CO ₂ Bz-(CH ₂ ) ₃ --CONHMe H 2- _{627 -CO 2 Bz - (CH 2} ) 3 - -CON (Me) 2 H 2-628 -CO 2 Bz - (CH 2) 3 - -CO 2 HH 2-629 -CO 2 Bz - (CH 2) 3 --CO ₂ Me H 2-630 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ Et H 2-631 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ (CH ₂ ) ₂ Br H . [Table 3]

[0057]

Embedded image Compd. R ¹ R ² R ^3a AR ⁵ 3-1 -HH -Me -CONH ₂ H 3-2 -HH -Me -CONHMe H 3-3 -HH -Me -CON (Me) ₂ H 3-4 -HH -Me -CO ₂ HH 3-5- HH -Me -CO ₂ Me H 3-6 -HH -Me -CO ₂ Et H 3-7 -HH -iBu -CO ₂ Me H 3-8 -HH -Bz -CO ₂ Me H 3-9 -HH- CH ₂ OtBu -CO ₂ Me H 3-10 -HH -CH ₂ CO ₂ tBu -CO ₂ Me H 3-11 -Me H -Me -CONH ₂ H 3-12 -Me H -Me -CONHMe H 3-13 -Me H -Me -CON (Me) ₂ H 3-14 -Me H -Me -CO ₂ HH 3-15 -Me H -Me -CO ₂ Me H 3-16 -Me H -Me -CO ₂ Et H 3-17 -Me H -iBu -CO ₂ Me H 3-18 -Me H -Bz -CO ₂ Me H 3-19 -Me H -CH ₂ OtBu -CO ₂ Me H 3-20 -Me H -CH ₂ CO ₂ tBu -CO ₂ Me H 3-21 -Ph H -Me -CONH ₂ H 3-22 -Ph H -Me -CONHMe H 3-23 -Ph H -Me -CON (Me) ₂ H 3-24- Ph H -Me -CO ₂ HH 3-25 -Ph H -Me -CO ₂ Me H 3-26 -Ph H -Me -CO ₂ Et H 3-27 -Ph H -iBu -CO ₂ Me H 3-28 -Ph H -Bz -CO ₂ Me H 3-29 -Ph H -CH ₂ OtBu -CO ₂ Me H 3-30 -Ph H -CH ₂ CO ₂ tBu -CO ₂ Me H 3-31 -Ac H -Me -CONH ₂ H 3-32 -Ac H -Me -CONHMe H 3-33 -Ac H -Me -CON (Me) ₂ H 3-34 -Ac H -Me -CO ₂ HH 3-35 -Ac H -Me -CO ₂ Me H 3-36 -Ac H -Me -CO ₂ Et H 3-37 -Ac H -iBu -CO ₂ Me H 3-38 -Ac H -Bz -C O ₂ Me H 3-39 -Ac H -CH ₂ OtBu -CO ₂ Me H 3-40 -Ac H -CH ₂ CO ₂ tBu -CO ₂ Me H 3-41 -CO ₂ tBu H -H -CONH ₂ H _{3-42 -CO 2 tBu H -H -CONHMe H} 3-43 -CO 2 tBu H -H -CON (Me) 2 H 3-44 -CO 2 tBu H -H -CO 2 HH 3-45 -CO 2 tBu H -H -CO ₂ Me H 3-46 -CO ₂ tBu H -H -CO ₂ Et H 3-47 -CO ₂ tBu H -Me -CONH ₂ H 3-48 -CO ₂ tBu H -Me -CONHMe H 3-49 -CO ₂ tBu H -Me -CON (Me) ₂ H 3-50 -CO ₂ tBu H -Me -CONHBu H 3-51 -CO ₂ tBu H -Me -CON (Bu) ₂ H 3- 52 -CO ₂ tBu H -Me -CO-Pyrd (1) H 3-53 -CO ₂ tBu H -Me -CONH (2-CO ₂ Me-Ph) H 3-54 -CO ₂ tBu H -Me -CONH (3-CO ₂ H-Ph) H 3-55 -CO ₂ tBu H -Me -CONH (3-CO ₂ Me-Ph) H 3-56 -CO ₂ tBu H -Me -CONH (4-CO ₂ H -Ph) H 3-57 -CO ₂ tBu H -Me -CONH (4-CO ₂ Me-Ph) H 3-58 -CO ₂ tBu H -Me -CO ₂ HH 3-59 -CO ₂ tBu H -Me -CO ₂ Me H 3-60 -CO ₂ tBu H -Me -CO ₂ Et H 3-61 -CO ₂ tBu H -Me -CO ₂ Bz H 3-62 -CO ₂ tBu H -Me -CO ₂ H 2 -Me 3-63 -CO ₂ tBu H -Me -CO ₂ H 2-Me 5-Me 3-64 -CO ₂ tBu H -Me -CO ₂ H 2-OMe 5-Me 3-65 -CO ₂ tBu H -Me -CO ₂ Me 2-Me 3-66 -CO ₂ tBu H -Me -CO ₂ Me 2-Me 5-Me 3-67 -CO ₂ tBu H -Me -CO ₂ Me 2-OMe 5-Me 3-68 -CO ₂ tBu Me -Me -CONHMe H 3-69 -CO ₂ tBu Me -Me -CONHBu H 3-70 -CO ₂ tBu Me -Me- CON (Me) ₂ H 3-71 -CO ₂ tBu Me -Me -CON (Bu) ₂ H 3-72 -CO ₂ tBu Me -Me -CO ₂ HH 3-73 -CO ₂ tBu Me -Me -CO ₂ Me H 3-74 -CO ₂ tBu H -iPr -CONH ₂ H 3-75 -CO ₂ tBu H -iPr -CONHMe H 3-76 -CO ₂ tBu H -iPr -CON (Me) ₂ H 3-77- CO ₂ tBu H -iPr -CO ₂ HH 3-78 -CO ₂ tBu H -iPr -CO ₂ Me H 3-79 -CO ₂ tBu H -iPr -CO ₂ Et H 3-80 -CO ₂ tBu H -iBu -CONH ₂ H 3-81 -CO ₂ tBu H -iBu -CONHMe H 3-82 -CO ₂ tBu H -iBu -CON (Me) ₂ H 3-83 -CO ₂ tBu H -iBu -CONHBu H 3-84 -CO ₂ tBu H -iBu -CON (Bu) ₂ H 3-85 -CO ₂ tBu H -iBu -CO-Pyrd (1) H 3-86 -CO ₂ tBu H -iBu -CONH (2-CO ₂ Me -Ph) H 3-87 -CO ₂ tBu H -iBu -CONH (3-CO ₂ Me-Ph) H 3-88 -CO ₂ tBu H -iBu -CONH (4-CO ₂ Me-Ph) H 3- _{89 -CO 2 tBu H -iBu -CO 2} HH 3-90 -CO 2 tBu H -iBu -CO 2 Me H 3-91 -CO 2 tBu H -iBu -CO 2 Et H 3-92 -CO 2 tBu H -iBu -CO ₂ Bz H 3-93 -CO ₂ tBu H -iBu -CO ₂ H 2-Me 3-94 -CO ₂ tBu H -iBu -CO ₂ H 2-Me 5-Me 3-95 -CO ₂ tBu H -iBu -CO ₂ H 2-OMe 5-Me 3-96 -CO ₂ tBu H -iBu -CO ₂ Me 2-Me 3-97 -CO ₂ tBu H -iBu -CO ₂ Me 2-Me 5-Me 3-98 -CO ₂ tBu H -iBu -CO ₂ Me 2-OMe 5-Me 3-99 -CO ₂ tBu H -Ph -CONH ₂ H 3-100 -CO ₂ tBu H -Ph -CONHMe H 3-101 -CO ₂ tBu H -Ph -CON (Me) ₂ H 3-102 -CO ₂ tBu H -Ph -CO ₂ HH 3-103 -CO ₂ tBu H -Ph -CO ₂ Me H 3-104 -CO ₂ tBu H -Ph -CO ₂ Et H 3-105 -CO ₂ tBu H -Bz -CONH ₂ H 3-106 -CO ₂ tBu H -Bz -CONHMe H 3-107 -CO ₂ tBu H -Bz -CON (Me) ₂ H 3-108 -CO ₂ tBu H -Bz- CONHBu H 3-109 -CO ₂ tBu H -Bz -CON (Bu) ₂ H 3-110 -CO ₂ tBu H -Bz -CO-Pyrd (1) H 3-111 -CO ₂ tBu H -Bz -CONH ( 2-CO ₂ Me-Ph) H 3-112 -CO ₂ tBu H -Bz -CONH (3-CO ₂ Me-Ph) H 3-113 -CO ₂ tBu H -Bz -CONH (4-CO ₂ Me- Ph) H 3-114 -CO ₂ tBu H -Bz -CO ₂ HH 3-115 -CO ₂ tBu H -Bz -CO ₂ Me H 3-116 -CO ₂ tBu H -Bz -CO ₂ Et H 3-117 _{-CO 2 tBu H -Bz -CO 2 Bz} H 3-118 -CO 2 tBu H -Bz -CO 2 H 2-Me 3-119 -CO 2 tBu H -Bz -CO 2 H 2-Me 5-Me 3 _{-120 -CO 2 tBu H -Bz -CO 2} H 2-OMe 5-Me 3-121 -CO 2 tBu H -Bz -CO 2 Me 2-Me 3-122 -CO 2 tBu H -Bz -CO 2 Me 2-Me 5-Me 3-123 -CO ₂ tBu H -Bz -CO ₂ Me 2-OMe 5-Me 3-124 -CO ₂ tBu H -CH ₂ -Ind (3) -CONH ₂ H 3-125 -CO ₂ tBu H -CH ₂ -Ind (3) -CONHMe H 3-126- CO ₂ tBu H -CH ₂ -Ind (3) -CON (Me) ₂ H 3-127 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ HH 3-128 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Me H 3-129 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Et H 3-130 -CO ₂ tBu H -CH ₂ OtBu -CONH ₂ H 3-131 -CO ₂ tBu H -CH ₂ OtBu -CONHMe H 3-132 -CO ₂ tBu H -CH ₂ OtBu -CON (Me) ₂ H 3-133 -CO ₂ tBu H -CH ₂ OtBu -CONHBu H 3-134- CO ₂ tBu H -CH ₂ OtBu -CON (Bu) ₂ H 3-135 -CO ₂ tBu H -CH ₂ OtBu -CO-Pyrd (1) H 3-136 -CO ₂ tBu H -CH ₂ OtBu -CONH ( 2-CO ₂ Me-Ph) H 3-137 -CO ₂ tBu H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 3-138 -CO ₂ tBu H -CH ₂ OtBu -CONH (4- (CO ₂ Me-Ph) H 3-139 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ HH 3-140 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me H 3-141 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Et H 3-142 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Bz H 3-143 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-Me 3-144 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-Me 5-Me 3-145 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-OMe 5-Me 3-146 -CO ₂ tBu H -CH ₂ OtBu- CO ₂ Me 2-Me 3-147 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-Me 5-Me 3-148 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-OMe 5-Me 3-149 -CO ₂ tBu H -CH (Me) OtBu -CONH ₂ H 3-150 -CO ₂ tBu H -CH (Me) OtBu -CONHMe H 3-151 -CO ₂ tBu H -CH (Me) OtBu -CON (Me ) ₂ H 3-152 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ HH 3-153 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Me H 3-154 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Et H 3-155 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CONH ₂ H 3-156 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CONHMe H 3-157- CO ₂ tBu H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 3-158 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ HH 3-159 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Me H 3-160 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Et H 3-161 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH ₂ H 3-162 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHMe H 3-163 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 3-164 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHBu H 3-165 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 3-166 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 3-167 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 3-168 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 3-169 -CO ₂ tB u H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 3-170 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ HH 3-171 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me H 3-172 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Et H 3-173 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Bz H 3-174 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 3-175 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-Me 3-176 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-OMe 5-Me 3-177 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 3-178 -CO ₂ tBu H -CH ₂ CO ₂ tBu- CO ₂ Me 2-Me 5-Me 3-179 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-OMe 5-Me 3-180 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu _{-CONH 2 H 3-181 -CO 2 tBu H} - (CH 2) 2 CO 2 tBu -CONHMe H 3-182 -CO 2 tBu H - (CH 2) 2 CO 2 tBu -CON (Me) 2 H 3- 183 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 3-184 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 3-185 -CO ₂ tBu H- (CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 3-186 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 3-187 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 3-188 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 3-189 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 3-190 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 3-191 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 3-192- CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONH ₂ H 3-193 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONHMe H 3-194 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 3-195 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ HH 3-196 -CO ₂ tBu H -CH ₂ (4- BzO-Ph) -CO ₂ Me H 3-197 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 3-198 -CO ₂ Bz H -H -CONH ₂ H 3-199- CO ₂ Bz H -H -CONHMe H 3-200 -CO ₂ Bz H -H -CON (Me) ₂ H 3-201 -CO ₂ Bz H -H -CO ₂ HH 3-202 -CO ₂ Bz H -H -CO ₂ Me H 3-203 -CO ₂ Bz H -H -CO ₂ Et H 3-204 -CO ₂ Bz H -Me -CONH ₂ H 3-205 -CO ₂ Bz H -Me -CONHMe H 3-206 -CO ₂ Bz H -Me -CON (Me) ₂ H 3-207 -CO ₂ Bz H -Me -CONHBu H 3-208 -CO ₂ Bz H -Me -CON (Bu) ₂ H 3-209 -CO ₂ Bz H -Me -CO-Pyrd (1) H 3-210 -CO ₂ Bz H -Me -CONH (2-CO ₂ Me-Ph) H 3-211 -CO ₂ Bz H -Me -CONH (3-CO ₂ H-Ph) H 3-212 -CO ₂ Bz H -Me -CONH (3-CO ₂ Me-Ph) H 3-213 -CO ₂ Bz H -Me -CONH (4-CO ₂ H-Ph) H 3-214 -CO ₂ Bz H -Me -CONH (4-CO ₂ Me-Ph) H 3-215 -CO ₂ Bz H -Me -CO ₂ HH 3-216 -CO ₂ Bz H -Me -CO ₂ Me H 3-217 -CO ₂ Bz H -Me -CO ₂ Et H 3-218 -CO ₂ Bz H -Me -CO ₂ Bz H 3-219- CO ₂ Bz H -Me -CO ₂ H 2-Me 3-220 -CO ₂ Bz H -Me -CO ₂ H 2-Me 5-Me 3-221 -CO ₂ Bz H -Me -CO ₂ H 2-OMe 5-Me 3-222 -CO ₂ Bz H -Me -CO ₂ Me 2-Me 3-223 -CO ₂ Bz H -Me -CO ₂ Me 2-Me 5-Me 3-224 -CO ₂ Bz H -Me -CO ₂ Me 2-OMe 5-Me 3-225 -CO ₂ Bz Me -Me -CONHMe H 3-226 -CO ₂ Bz Me -Me -CONHBu H 3-227 -CO ₂ Bz Me -Me -CON (Me ) ₂ H 3-228 -CO ₂ Bz Me -Me -CON (Bu) ₂ H 3-229 -CO ₂ Bz Me -Me -CO ₂ HH 3-230 -CO ₂ Bz Me -Me -CO ₂ Me H 3 -231 -CO ₂ Bz H -iPr -CONH ₂ H 3-232 -CO ₂ Bz H -iPr -CONHMe H 3-233 -CO ₂ Bz H -iPr -CON (Me) ₂ H 3-234 -CO ₂ Bz H -iPr -CO ₂ HH 3-235 -CO ₂ Bz H -iPr -CO ₂ Me H 3-236 -CO ₂ Bz H -iPr -CO ₂ Et H 3-237 -CO ₂ Bz H -iBu -CONH ₂ H 3-238 -CO ₂ Bz H -iBu -CONHMe H 3-239 -CO ₂ Bz H -iBu -CON (Me) ₂ H 3-240 -CO ₂ Bz H -iBu -CONHBu H 3-241 -CO ₂ Bz H -iBu -CON (Bu) ₂ H 3-242 -CO ₂ Bz H -iBu -CO-Pyrd (1) H 3-243 -CO ₂ Bz H -iBu -CONH (2-CO ₂ Me-Ph) H 3-244 -CO ₂ Bz H -iBu -CONH (3-CO ₂ Me-Ph) H 3-245 -CO ₂ Bz H -iBu -CONH (4-CO ₂ Me-Ph) H 3-246 -CO ₂ Bz H -iBu -CO ₂ HH 3-247 -CO ₂ Bz H -iBu -CO ₂ Me H 3-248 -CO ₂ Bz H -iBu -CO ₂ Et H 3-249 -CO ₂ Bz H -iBu -CO ₂ Bz H 3-250 -CO ₂ Bz H -iBu -CO ₂ H 2-Me 3-251 -CO ₂ Bz H -iBu -CO ₂ H 2-Me 5-Me 3-252 -CO ₂ Bz H -iBu -CO ₂ H 2-OMe 5-Me 3-253 -CO ₂ Bz H -iBu -CO ₂ Me 2-Me 3-254 -CO ₂ Bz H -iBu -CO ₂ Me 2-Me 5-Me 3-255 -CO ₂ Bz H -iBu -CO ₂ Me 2-OMe 5- Me 3-256 -CO ₂ Bz H -Ph -CONH ₂ H 3-257 -CO ₂ Bz H -Ph -CONHMe H 3-258 -CO ₂ Bz H -Ph -CON (Me) ₂ H 3-259 -CO ₂ Bz H -Ph -CO ₂ HH 3-260 -CO ₂ Bz H -Ph -CO ₂ Me H 3-261 -CO ₂ Bz H -Ph -CO ₂ Et H 3-262 -CO ₂ Bz H -Bz- CONH ₂ H 3-263 -CO ₂ Bz H -Bz -CONHMe H 3-264 -CO ₂ Bz H -Bz -CON (Me) ₂ H 3-265 -CO ₂ Bz H -Bz -CONHBu H 3-266- CO ₂ Bz H -Bz -CON (Bu) ₂ H 3-267 -CO ₂ Bz H -Bz -CO-Pyrd (1) H 3-268 -CO ₂ Bz H -Bz -CONH (2-CO ₂ Me- Ph) H 3-269 -CO ₂ Bz H -Bz -CONH (3-CO ₂ Me-Ph) H 3-270 -CO ₂ Bz H -Bz -CONH (4-CO ₂ Me-Ph) H 3-271 -CO ₂ Bz H -Bz -CO ₂ HH 3-272 -CO ₂ Bz H -Bz -CO ₂ Me H 3- 273 -CO ₂ Bz H -Bz -CO ₂ Et H 3-274 -CO ₂ Bz H -Bz -CO ₂ Bz H 3-275 -CO ₂ Bz H -Bz -CO ₂ H 2-Me 3-276 -CO ₂ Bz H -Bz -CO ₂ H 2-Me 5-Me 3-277 -CO ₂ Bz H -Bz -CO ₂ H 2-OMe 5-Me 3-278 -CO ₂ Bz H -Bz -CO ₂ Me 2 -Me 3-279 -CO ₂ Bz H -Bz -CO ₂ Me 2-Me 5-Me 3-280 -CO ₂ Bz H -Bz -CO ₂ Me 2-OMe 5-Me 3-281 -CO ₂ Bz H -CH ₂ -Ind (3) -CONH ₂ H 3-282 -CO ₂ Bz H -CH ₂ -Ind (3) -CONHMe H 3-283 -CO ₂ Bz H -CH ₂ -Ind (3) -CON ( Me) ₂ H 3-284 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ HH 3-285 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Me H 3-286 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Et H 3-287 -CO ₂ Bz H -CH ₂ OtBu -CONH ₂ H 3-288 -CO ₂ Bz H -CH ₂ OtBu -CONHMe H 3-289 -CO ₂ Bz H -CH ₂ OtBu -CON (Me) ₂ H 3-290 -CO ₂ Bz H -CH ₂ OtBu -CONHBu H 3-291 -CO ₂ Bz H -CH ₂ OtBu -CON (Bu) ₂ H 3-292 -CO ₂ Bz H -CH ₂ OtBu -CO-Pyrd (1) H 3-293 -CO ₂ Bz H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 3-294 -CO ₂ Bz H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 3-295 -CO ₂ Bz H -CH ₂ OtBu -CONH (4-CO ₂ Me-Ph) H 3-296 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ HH 3-297 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me H 3-298 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Et H 3-299 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Bz H 3-300 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-Me 3-301 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-Me 5-Me 3-302 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-OMe 5-Me 3 -303 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-Me 3-304 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-Me 5-Me 3-305 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-OMe 5-Me 3-306 -CO ₂ Bz H -CH (Me) OtBu -CONH ₂ H 3-307 -CO ₂ Bz H -CH (Me) OtBu -CONHMe H 3-308 -CO ₂ Bz H -CH (Me) OtBu -CON (Me) ₂ H 3-309 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ HH 3-310 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Me H 3-311 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Et H 3-312 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONH ₂ H 3-313 -CO ₂ Bz _{H - (CH 2) 2 SMe} -CONHMe H 3-314 -CO 2 Bz H - (CH 2) 2 SMe -CON (Me) 2 H 3-315 -CO 2 Bz H - (CH 2) 2 SMe -CO ₂ HH 3-316 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Me H 3-317 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Et H 3-318 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH ₂ H 3-319 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHMe H 3-320 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 3- 321 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHBu H 3-322 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 3-323 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 3 -324 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 3-325 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 3-326 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 3-327 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ HH 3-328 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me H 3-329 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Et H 3-330 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Bz H 3-331 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 3-332 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-Me 3-333 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-OMe 5-Me 3-334 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 3-335 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 5-Me 3-336 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-OMe 5-Me 3-337 -CO ₂ Bz H-( CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 3-338 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 3-339 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 3-340 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 3-341 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 3- 342 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 3-343 -CO ₂ Bz H-(CH ₂ ) ₂ NHCO ₂ Bz -CO ₂ Me H 3-344 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 3-345 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 3-346 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 3-347- CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 3-348 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 3-349 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 3-350 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONH ₂ H 3-351 -CO ₂ Bz H -CH ₂ (4-BzO-Ph ) -CONHMe H 3-352 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 3-353 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ HH 3-354 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 3-355 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 3-356 _{-CO 2 tBu - (CH 2)} 3 - -CONH 2 H 3-357 -CO 2 tBu - (CH 2) 3 - -CONHMe H 3-358 -CO 2 tBu - (CH 2) 3 - -CON (Me ) ₂ H 3-359 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ HH 3-360 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ Me H 3-361 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ Et H 3-362 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ (CH ₂ ) ₂ Br H 3-363 -CO ₂ Bz-(CH ₂ ) ₃ --CONH ₂ H 3-364 -CO ₂ Bz-(CH ₂ ) ₃ --CONHMe H 3-36 _{5 -CO 2 Bz - (CH 2} ) 3 - -CON (Me) 2 H 3-366 -CO 2 Bz - (CH 2) 3 - -CO 2 HH 3-367 -CO 2 Bz - (CH 2) 3 --CO ₂ Me H 3-368 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ Et H 3-369 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ (CH ₂ ) ₂ Br H . [Table 4]

[0058]

Embedded image Compd. R ¹ R ² R ^3a AR ⁵ 4-1 -HH -Me -CONH ₂ H 4-2 -HH -Me -CONHMe H 4-3 -HH -Me -CON (Me) ₂ H 4-4 -HH -Me -CO ₂ HH 4-5- HH -Me -CO ₂ Me H 4-6 -HH -Me -CO ₂ Et H 4-7 -HH -Me -CO ₂ (CH ₂ ) ₂ Br H 4-8 -HH -iBu -CO ₂ Me H 4 -9 -HH -Bz -CO ₂ Me H 4-10 -HH -CH ₂ OtBu -CO ₂ Me H 4-11 -HH -CH ₂ CO ₂ tBu -CO ₂ Me H 4-12 -Me H -Me- CONH ₂ H 4-13 -Me H -Me -CONHMe H 4-14 -Me H -Me -CON (Me) ₂ H 4-15 -Me H -Me -CO ₂ HH 4-16 -Me H -Me- CO ₂ Me H 4-17 -Me H -Me -CO ₂ Et H 4-18 -Me H -Me -CO ₂ (CH ₂ ) ₂ Br H 4-19 -Me H -iBu -CO ₂ Me H 4- 20 -Me H -Bz -CO ₂ Me H 4-21 -Me H -CH ₂ OtBu -CO ₂ Me H 4-22 -Me H -CH ₂ CO ₂ tBu -CO ₂ Me H 4-23 -Ph H- Me -CONH ₂ H 4-24 -Ph H -Me -CONHMe H 4-25 -Ph H -Me -CON (Me) ₂ H 4-26 -Ph H -Me -CO ₂ HH 4-27 -Ph H- Me -CO ₂ Me H 4-28 -Ph H -Me -CO ₂ Et H 4-29 -Ph H -Me -CO ₂ (CH ₂ ) ₂ Br H 4-30 -Ph H -iBu -CO ₂ Me H 4-31 -Ph H -Bz -CO ₂ Me H 4-32 -Ph H -CH ₂ OtBu -CO ₂ Me H 4-33 -Ph H -CH ₂ CO ₂ tBu -CO ₂ Me H 4-34 -Ac H -Me -CONH ₂ H 4-35 -Ac H -Me -CONHMe H 4-36 -Ac H -Me -CON (Me) ₂ H 4-37 -Ac H -Me -CO ₂ HH 4-38 -Ac H -Me -CO ₂ Me H 4-39 -Ac H -Me -CO ₂ Et H 4-40 -Ac H -Me -CO ₂ (CH ₂ ) ₂ Br H 4- 41 -Ac H -iBu -CO ₂ Me H 4-42 -Ac H -Bz -CO ₂ Me H 4-43 -Ac H -CH ₂ OtBu -CO ₂ Me H 4-44 -Ac H -CH ₂ CO _{2 tBu -CO 2 Me H 4-45 -CO 2} tBu H -H -CONH 2 H 4-46 -CO 2 tBu H -H -CONHMe H 4-47 -CO 2 tBu H -H -CON (Me) 2 H 4-48 -CO ₂ tBu H -H -CO ₂ HH 4-49 -CO ₂ tBu H -H -CO ₂ Me H 4-50 -CO ₂ tBu H -H -CO ₂ Et H 4-51 -CO _{2 tBu H -Me -CONH 2 H 4-52 -CO} 2 tBu H -Me -CONHMe H 4-53 -CO 2 tBu H -Me -CON (Me) 2 H 4-54 -CO 2 tBu H -Me -CONHBu H 4-55 -CO ₂ tBu H -Me -CON (Bu) ₂ H 4-56 -CO ₂ tBu H -Me -CO-Pyrd (1) H 4-57 -CO ₂ tBu H -Me -CONH (2 -CO ₂ Me-Ph) H 4-58 -CO ₂ tBu H -Me -CONH (3-CO ₂ H-Ph) H 4-59 -CO ₂ tBu H -Me -CONH (3-CO ₂ Me-Ph ) H 4-60 -CO ₂ tBu H -Me -CONH (4-CO ₂ H-Ph) H 4-61 -CO ₂ tBu H -Me -CONH (4-CO ₂ Me-Ph) H 4-62- CO ₂ tBu H -Me -CO ₂ HH 4-63 -CO ₂ tBu H -Me -CO ₂ Me H 4-64 -CO ₂ tBu H -Me -CO ₂ Et H 4-65 -CO ₂ tBu H -Me -CO ₂ Bz H 4-66 -CO ₂ tBu H -Me -CO ₂ (CH ₂ ) ₂ Br H 4-67 -CO ₂ tBu H- Me -CO ₂ (CH ₂ ) ₂ Cl H 4-68 -CO ₂ tBu H -Me -CO ₂ H 6-Me 4-69 -CO ₂ tBu H -Me -CO ₂ H 5-Me 6-Me 4- 70 -CO ₂ tBu H -Me -CO ₂ H 6-OMe 5-Me 4-71 -CO ₂ tBu H -Me -CO ₂ Me 6-Me 4-72 -CO ₂ tBu H -Me -CO ₂ Me 6 -Me 5-Me 4-73 -CO ₂ tBu H -Me -CO ₂ Me 6-OMe 5-Me 4-74 -CO ₂ tBu Me -Me -CONHMe H 4-75 -CO ₂ tBu Me -Me -CONHBu H 4-76 -CO ₂ tBu Me -Me -CON (Me) ₂ H 4-77 -CO ₂ tBu Me -Me -CON (Bu) ₂ H 4-78 -CO ₂ tBu Me -Me -CO ₂ HH 4 -79 -CO ₂ tBu Me -Me -CO ₂ Me H 4-80 -CO ₂ tBu H -iPr -CONH ₂ H 4-81 -CO ₂ tBu H -iPr -CONHMe H 4-82 -CO ₂ tBu H- iPr -CON (Me) ₂ H 4-83 -CO ₂ tBu H -iPr -CO ₂ HH 4-84 -CO ₂ tBu H -iPr -CO ₂ Me H 4-85 -CO ₂ tBu H -iPr -CO ₂ Et H 4-86 -CO ₂ tBu H -iBu -CONH ₂ H 4-87 -CO ₂ tBu H -iBu -CONHMe H 4-88 -CO ₂ tBu H -iBu -CON (Me) ₂ H 4-89- CO ₂ tBu H -iBu -CONHBu H 4-90 -CO ₂ tBu H -iBu -CON (Bu) ₂ H 4-91 -CO ₂ tBu H -iBu -CO-Pyrd (1) H 4-92 -CO ₂ tBu H -iBu -CONH (2-CO ₂ Me-Ph) H 4-93 -CO ₂ tBu H -iBu -CONH (3-CO ₂ Me-Ph) H 4-94 -CO ₂ tBu H -iBu -CONH (4-CO ₂ Me-Ph) H 4-95 -CO ₂ tBu H -i Bu -CO ₂ HH 4-96 -CO ₂ tBu H -iBu -CO ₂ Me H 4-97 -CO ₂ tBu H -iBu -CO ₂ Et H 4-98 -CO ₂ tBu H -iBu -CO ₂ Bz H 4-99 -CO ₂ tBu H -iBu -CO ₂ (CH ₂ ) ₂ Br H 4-100 -CO ₂ tBu H -iBu -CO ₂ H 6-Me 4-101 -CO ₂ tBu H -iBu -CO ₂ H 6-Me 5-Me 4-102 -CO 2 tBu H -iBu -CO 2 H 6-OMe 5-Me 4-103 -CO 2 tBu H -iBu -CO 2 Me 6-Me 4-104 -CO 2 tBu H -iBu -CO ₂ Me 6-Me 5-Me 4-105 -CO ₂ tBu H -iBu -CO ₂ Me 6-OMe 5-Me 4-106 -CO ₂ tBu H -Ph -CONH ₂ H 4- 107 -CO ₂ tBu H -Ph -CONHMe H 4-108 -CO ₂ tBu H -Ph -CON (Me) ₂ H 4-109 -CO ₂ tBu H -Ph -CO ₂ HH 4-110 -CO ₂ tBu H -Ph -CO ₂ Me H 4-111 -CO ₂ tBu H -Ph -CO ₂ Et H 4-112 -CO ₂ tBu H -Bz -CONH ₂ H 4-113 -CO ₂ tBu H -Bz -CONHMe H 4 -114 -CO ₂ tBu H -Bz -CON (Me) ₂ H 4-115 -CO ₂ tBu H -Bz -CONHBu H 4-116 -CO ₂ tBu H -Bz -CON (Bu) ₂ H 4-117- CO ₂ tBu H -Bz -CO-Pyrd (1) H 4-118 -CO ₂ tBu H -Bz -CONH (2-CO ₂ Me-Ph) H 4-119 -CO ₂ tBu H -Bz -CONH (3 -CO ₂ Me-Ph) H 4-120 -CO ₂ tBu H -Bz -CONH (4-CO ₂ Me-Ph) H 4-121 -CO ₂ tBu H -Bz -CO ₂ HH 4-122 -CO ₂ tBu H -Bz -CO ₂ Me H 4-123 -CO ₂ tBu H -Bz -CO ₂ Et H 4-124 -CO ₂ tBu H -Bz -CO ₂ Bz H 4-125 -CO ₂ tBu H -Bz -CO ₂ (CH ₂ ) ₂ Br H 4-126 -CO ₂ tBu H -Bz -CO ₂ H 6-Me 4-127 -CO ₂ tBu H -Bz -CO ₂ H 6-Me 5-Me 4-128 -CO ₂ tBu H -Bz -CO ₂ H 6-OMe 5- Me 4-129 -CO ₂ tBu H -Bz -CO ₂ Me 6-Me 4-130 -CO ₂ tBu H -Bz -CO ₂ Me 6-Me 5-Me 4-131 -CO ₂ tBu H -Bz -CO ₂ Me 6-OMe 5-Me 4-132 -CO ₂ tBu H -CH ₂ -Ind (3) -CONH ₂ H 4-133 -CO ₂ tBu H -CH ₂ -Ind (3) -CONHMe H 4-134 -CO ₂ tBu H -CH ₂ -Ind (3) -CON (Me) ₂ H 4-135 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ HH 4-136 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Me H 4-137 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Et H 4-138 -CO ₂ tBu H -CH ₂ OtBu -CONH ₂ H 4- 139 -CO ₂ tBu H -CH ₂ OtBu -CONHMe H 4-140 -CO ₂ tBu H -CH ₂ OtBu -CON (Me) ₂ H 4-141 -CO ₂ tBu H -CH ₂ OtBu -CONHBu H 4-142 -CO ₂ tBu H -CH ₂ OtBu -CON (Bu) ₂ H 4-143 -CO ₂ tBu H -CH ₂ OtBu -CO-Pyrd (1) H 4-144 -CO ₂ tBu H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 4-145 -CO ₂ tBu H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 4-146 -CO ₂ tBu H -CH ₂ OtBu -CONH (4 -CO ₂ Me-Ph) H 4-147 -CO ₂ tB u H -CH ₂ OtBu -CO ₂ HH 4-148 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me H 4-149 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Et H 4-150 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Bz H 4-151 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ (CH ₂ ) ₂ Br H 4-152 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 6 -Me 4-153 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 6-Me 5-Me 4-154 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 6-OMe 5-Me 4-155- CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 6-Me 4-156 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 6-Me 5-Me 4-157 -CO ₂ tBu H -CH ₂ OtBu- CO ₂ Me 6-OMe 5-Me 4-158 -CO ₂ tBu H -CH (Me) OtBu -CONH ₂ H 4-159 -CO ₂ tBu H -CH (Me) OtBu -CONHMe H 4-160 -CO ₂ tBu H -CH (Me) OtBu -CON (Me) ₂ H 4-161 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ HH 4-162 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Me H 4-163 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Et H 4-164 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CONH ₂ H 4-165 -CO ₂ tBu H-( CH ₂ ) ₂ SMe -CONHMe H 4-166 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 4-167 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ HH 4 -168 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Me H 4-169 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Et H 4-170 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH ₂ H 4-171 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHMe H 4-172 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 4-173 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHBu H 4-174 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 4-175 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO- Pyrd (1) H 4-176 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 4-177 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (3- (CO ₂ Me-Ph) H 4-178 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 4-179 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ HH 4-180 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me H 4-181 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Et H 4-182 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Bz H 4-183 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ (CH ₂ ) ₂ Br H 4-184 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 6-Me 4-185 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 6-Me 5-Me 4-186 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 6-OMe 5- Me 4-187 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 6-Me 4-188 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 6-Me 5-Me 4-189- CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 6-OMe 5-Me 4-190 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 4-191 -CO ₂ t Bu H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 4-192 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 4-193 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 4-194 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 4-195 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 4-196 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 4-197 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 4-198 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 4-199 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 4-200 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 4-201 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 4-202 -CO ₂ tBu H -CH ₂ (4-BzO-Ph ) -CONH ₂ H 4-203 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONHMe H 4-204 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 4-205 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ HH 4-206 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 4-207- CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 4-208 -CO ₂ tBu-(CH ₂ ) ₃ --CONH ₂ H 4-209 -CO ₂ tBu-(CH ₂ ) ₃ --CONHMe H 4-210 -CO ₂ tBu-(CH ₂ ) ₃ --CON (Me) ₂ H 4-211 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ HH 4-212 -CO ₂ tBu -(CH ₂ ) ₃ --CO ₂ Me H 4-213 -CO ₂ tBu-(CH ₂ ) ₃ --CO ₂ Et H 4-214 -CO ₂ Bz H -H -CONH ₂ H 4-215 -CO ₂ Bz H -H -CONHMe H 4-216- CO ₂ Bz H -H -CON (Me) ₂ H 4-217 -CO ₂ Bz H -H -CO ₂ HH 4-218 -CO ₂ Bz H -H -CO ₂ Me H 4-219 -CO ₂ Bz H _{-H -CO 2 Et H 4-220 -CO 2} Bz H -Me -CONH 2 H 4-221 -CO 2 Bz H -Me -CONHMe H 4-222 -CO 2 Bz H -Me -CON (Me) 2 H 4-223 -CO ₂ Bz H -Me -CONHBu H 4-224 -CO ₂ Bz H -Me -CON (Bu) ₂ H 4-225 -CO ₂ Bz H -Me -CO-Pyrd (1) H 4 -226 -CO ₂ Bz H -Me -CONH (2-CO ₂ Me-Ph) H 4-227 -CO ₂ Bz H -Me -CONH (3-CO ₂ H-Ph) H 4-228 -CO ₂ Bz H -Me -CONH (3-CO ₂ Me-Ph) H 4-229 -CO ₂ Bz H -Me -CONH (4-CO ₂ H-Ph) H 4-230 -CO ₂ Bz H -Me -CONH ( 4-CO ₂ Me-Ph) H 4-231 -CO ₂ Bz H -Me -CO ₂ HH 4-232 -CO ₂ Bz H -Me -CO ₂ Me H 4-233 -CO ₂ Bz H -Me -CO ₂ Et H 4-234 -CO ₂ Bz H -Me -CO ₂ Bz H 4-235 -CO ₂ Bz H -Me -CO ₂ H 6-Me 4-236 -CO ₂ Bz H -Me -CO ₂ H 6 -Me 5-Me 4-237 -CO ₂ Bz H -Me -CO ₂ H 6-OMe 5-Me 4-238 -CO ₂ Bz H -Me -CO ₂ Me 6-Me 4-239 -CO ₂ Bz H -Me -CO ₂ Me 6-Me 5-Me 4-240 -CO ₂ Bz H -Me -CO ₂ Me 6-OMe 5-Me 4-241 -CO ₂ Bz Me -Me -CONHMe H 4-242 -CO ₂ Bz Me -Me -CONHBu H 4-243 -CO ₂ Bz Me -Me -CON (Me) ₂ H 4-244 -CO ₂ Bz Me -Me -CON ( Bu) ₂ H 4-245 -CO ₂ Bz Me -Me -CO ₂ HH 4-246 -CO ₂ Bz Me -Me -CO ₂ Me H 4-247 -CO ₂ Bz H -iPr -CONH ₂ H 4-248 -CO ₂ Bz H -iPr -CONHMe H 4-249 -CO ₂ Bz H -iPr -CON (Me) ₂ H 4-250 -CO ₂ Bz H -iPr -CO ₂ HH 4-251 -CO ₂ Bz H- iPr -CO ₂ Me H 4-252 -CO ₂ Bz H -iPr -CO ₂ Et H 4-253 -CO ₂ Bz H -iPr -CO ₂ (CH ₂ ) ₂ Br H 4-254 -CO ₂ Bz H- iBu -CONH ₂ H 4-255 -CO ₂ Bz H -iBu -CONHMe H 4-256 -CO ₂ Bz H -iBu -CON (Me) ₂ H 4-257 -CO ₂ Bz H -iBu -CONHBu H 4- 258 -CO ₂ Bz H -iBu -CON (Bu) ₂ H 4-259 -CO ₂ Bz H -iBu -CO-Pyrd (1) H 4-260 -CO ₂ Bz H -iBu -CONH (2-CO ₂ Me-Ph) H 4-261 -CO ₂ Bz H -iBu -CONH (3-CO ₂ Me-Ph) H 4-262 -CO ₂ Bz H -iBu -CONH (4-CO ₂ Me-Ph) H 4 -263 -CO ₂ Bz H -iBu -CO ₂ HH 4-264 -CO ₂ Bz H -iBu -CO ₂ Me H 4-265 -CO ₂ Bz H -iBu -CO ₂ Et H 4-266 -CO ₂ Bz H -iBu -CO ₂ Bz H 4-267 -CO ₂ Bz H -iBu -CO ₂ (CH ₂ ) ₂ Br H 4-268 -CO ₂ Bz H -iBu -CO ₂ H 6-Me 4-269 -CO ₂ Bz H -iBu -CO ₂ H 6- Me 5-Me 4-270 -CO ₂ Bz H -iBu -CO ₂ H 6-OMe 5-Me 4-271 -CO ₂ Bz H -iBu -CO ₂ Me 6-Me 4-272 -CO ₂ Bz H- iBu -CO ₂ Me 6-Me 5-Me 4-273 -CO ₂ Bz H -iBu -CO ₂ Me 6-OMe 5-Me 4-274 -CO ₂ Bz H -Ph -CONH ₂ H 4-275 -CO ₂ Bz H -Ph -CONHMe H 4-276 -CO ₂ Bz H -Ph -CON (Me) ₂ H 4-277 -CO ₂ Bz H -Ph -CO ₂ HH 4-278 -CO ₂ Bz H -Ph- CO ₂ Me H 4-279 -CO ₂ Bz H -Ph -CO ₂ Et H 4-280 -CO ₂ Bz H -Ph -CO ₂ (CH ₂ ) ₂ Br H 4-281 -CO ₂ Bz H -Bz- CONH ₂ H 4-282 -CO ₂ Bz H -Bz -CONHMe H 4-283 -CO ₂ Bz H -Bz -CON (Me) ₂ H 4-284 -CO ₂ Bz H -Bz -CONHBu H 4-285- CO ₂ Bz H -Bz -CON (Bu) ₂ H 4-286 -CO ₂ Bz H -Bz -CO-Pyrd (1) H 4-287 -CO ₂ Bz H -Bz -CONH (2-CO ₂ Me- Ph) H 4-288 -CO ₂ Bz H -Bz -CONH (3-CO ₂ Me-Ph) H 4-289 -CO ₂ Bz H -Bz -CONH (4-CO ₂ Me-Ph) H 4-290 -CO ₂ Bz H -Bz -CO ₂ HH 4-291 -CO ₂ Bz H -Bz -CO ₂ Me H 4-292 -CO ₂ Bz H -Bz -CO ₂ Et H 4-293 -CO ₂ Bz H- Bz -CO ₂ Bz H 4-294 -CO ₂ Bz H -Bz -CO ₂ H 6-Me 4-295 -CO ₂ Bz H -Bz -CO ₂ H 6-Me 5-Me 4-296 -CO ₂ Bz H -Bz -CO ₂ H 6-OMe 5-Me 4-297 -CO ₂ Bz H -Bz -CO ₂ Me 6-Me 4 _{-298 -CO 2 Bz H -Bz -CO 2} Me 6-Me 5-Me 4-299 -CO 2 Bz H -Bz -CO 2 Me 6-OMe 5-Me 4-300 -CO 2 Bz H -Bz - CO ₂ (CH ₂ ) ₂ Br H 4-301 -CO ₂ Bz H -CH ₂ -Ind (3) -CONH ₂ H 4-302 -CO ₂ Bz H -CH ₂ -Ind (3) -CONHMe H 4- 303 -CO ₂ Bz H -CH ₂ -Ind (3) -CON (Me) ₂ H 4-304 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ HH 4-305 -CO ₂ Bz H- CH ₂ -Ind (3) -CO ₂ Me H 4-306 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Et H 4-307 -CO ₂ Bz H -CH ₂ -Ind (3)- CO ₂ (CH ₂ ) ₂ Br H 4-308 -CO ₂ Bz H -CH ₂ OtBu -CONH ₂ H 4-309 -CO ₂ Bz H -CH ₂ OtBu -CONHMe H 4-310 -CO ₂ Bz H -CH ₂ OtBu -CON (Me) ₂ H 4-311 -CO ₂ Bz H -CH ₂ OtBu -CONHBu H 4-312 -CO ₂ Bz H -CH ₂ OtBu -CON (Bu) ₂ H 4-313 -CO ₂ Bz H -CH ₂ OtBu -CO-Pyrd (1) H 4-314 -CO ₂ Bz H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 4-315 -CO ₂ Bz H -CH ₂ OtBu- CONH (3-CO ₂ Me-Ph) H 4-316 -CO ₂ Bz H -CH ₂ OtBu -CONH (4-CO ₂ Me-Ph) H 4-317 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ HH 4-318 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me H 4-319 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Et H 4-320 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Bz H 4-321 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ (CH ₂ ) ₂ Br H 4-322 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 6-Me 4-323 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 6-Me 5-Me 4- 324 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 6-OMe 5-Me 4-325 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 6-Me 4-326 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 6-Me 5-Me 4-327 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 6-OMe 5-Me 4-328 -CO ₂ Bz H -CH (Me) OtBu -CONH ₂ H 4-329 -CO ₂ Bz H -CH (Me) OtBu -CONHMe H 4-330 -CO ₂ Bz H -CH (Me) OtBu -CON (Me) ₂ H 4-331 -CO ₂ Bz H -CH ( Me) OtBu -CO ₂ HH 4-332 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Me H 4-333 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Et H 4-334 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ (CH ₂ ) ₂ Br H 4-335 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONH ₂ H 4-336 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONHMe H 4-337 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 4-338 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ HH 4-339 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Me H 4-340 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Et H 4-341 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ (CH ₂ ) ₂ Br H 4-342 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH ₂ H 4-343 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHMe H 4-344 -CO ₂ Bz H -CH ₂ CO ₂ tBu- CON (Me) ₂ H 4-345 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHBu H 4-346 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 4-347 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 4-348 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 4-349 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 4-350 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 4-351 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ HH 4-352 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me H 4-353 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Et H 4-354 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Bz H 4-355 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ (CH ₂ ) ₂ Br H 4-356 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 6-Me 4-357 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 6-Me 5-Me 4-358 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 6-OMe 5-Me 4-359 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 6-Me 4-360 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 6-Me 5-Me 4-361 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 6-OMe 5-Me 4-362 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 4-363 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 4-364 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 4-365- CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 4-366 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 4-367 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 4-368 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ (CH ₂ ) ₂ Br H 4-369 -CO ₂ Bz H-(CH ₂ ) ₂ NHCO ₂ Bz -CO ₂ Me H 4 -370 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 4-371 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 4-372 -CO ₂ Bz H-( CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 4-373 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 4-374 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 4-375 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 4-376 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ ( CH ₂ ) ₂ Br H 4-377 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONH ₂ H 4-378 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONHMe H 4 -379 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 4-380 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ HH 4-381- CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 4-382 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 4-383 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ (CH ₂ ) ₂ Br H 4-384 -CO ₂ Bz-(CH ₂ ) ₃ --CONH ₂ H 4-385 -CO ₂ Bz-(CH ₂ ) ₃ --CONHMe H 4-386 -CO ₂ Bz-(CH ₂ ) ₃ --CON (Me) ₂ H 4-387 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ HH 4-388 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ Me H 4-389 -CO ₂ Bz- (CH ₂ ) ₃ --CO ₂ Et H 4-390 -CO ₂ Bz-(CH ₂ ) ₃ --CO ₂ (CH ₂ ) ₂ Br H . [Table 5]

[0059]

Embedded image Compd. R ¹ R ² R ^3a AR ⁵ 5-1 -HH -Me -CONH ₂ H 5-2 -HH -Me -CONHMe H 5-3 -HH -Me -CON (Me) ₂ H 5-4 -HH -Me -CONHBu H 5-5 -HH -Me -CON (Bu) ₂ H 5-6 -HH -Me -CO-Pyrd (1) H 5-7 -HH -Me -CO ₂ HH 5-8 -HH -Me -CO ₂ Me H 5-9 -HH -Me -CO ₂ Et H 5-10 -HH -Me -CO ₂ Bz H 5-11 -HH -iBu -CO ₂ HH 5-12 -HH -iBu -CO ₂ Me H 5-13 -HH- Bz -CO ₂ HH 5-14 -HH -Bz -CO ₂ Me H 5-15 -HH -CH ₂ OtBu -CO ₂ HH 5-16 -HH -CH ₂ OtBu -CO ₂ Me H 5-17 -HH- CH ₂ CO ₂ tBu -CO ₂ HH 5-18 -HH -CH ₂ CO ₂ tBu -CO ₂ Me H 5-19 -Me H -Me -CONH ₂ H 5-20 -Me H -Me -CONHMe H 5- 21 -Me H -Me -CON (Me) ₂ H 5-22 -Me H -Me -CONHBu H 5-23 -Me H -Me -CON (Bu) ₂ H 5-24 -Me H -Me -CO- Pyrd (1) H 5-25 -Me H -Me -CO ₂ HH 5-26 -Me H -Me -CO ₂ Me H 5-27 -Me H -Me -CO ₂ Et H 5-28 -Me H- Me -CO ₂ Bz H 5-29 -Me H -iBu -CO ₂ HH 5-30 -Me H -iBu -CO ₂ Me H 5-31 -Me H -Bz -CO ₂ HH 5-32 -Me H- Bz -CO ₂ Me H 5-33 -Me H -CH ₂ OtBu -CO ₂ HH 5-34 -Me H -CH ₂ OtBu -CO ₂ Me H 5-35 -Me H -CH ₂ CO ₂ tBu -CO ₂ HH 5-36 -Me H -CH ₂ CO ₂ tBu -CO ₂ Me H 5-37 -Ph H -Me -CONH ₂ H 5-38 -Ph H -Me -CONH Me H 5-39 -Ph H -Me -CON (Me) ₂ H 5-40 -Ph H -Me -CONHBu H 5-41 -Ph H -Me -CON (Bu) ₂ H 5-42 -Ph H- Me -CO-Pyrd (1) H 5-43 -Ph H -Me -CO ₂ HH 5-44 -Ph H -Me -CO ₂ Me H 5-45 -Ph H -Me -CO ₂ Et H 5-46 -Ph H -Me -CO ₂ Bz H 5-47 -Ph H -iBu -CO ₂ HH 5-48 -Ph H -iBu -CO ₂ Me H 5-49 -Ph H -Bz -CO ₂ HH 5-50 -Ph H -Bz -CO ₂ Me H 5-51 -Ph H -CH ₂ OtBu -CO ₂ HH 5-52 -Ph H -CH ₂ OtBu -CO ₂ Me H 5-53 -Ph H -CH ₂ CO ₂ tBu -CO ₂ HH 5-54 -Ph H -CH ₂ CO ₂ tBu -CO ₂ Me H 5-55 -Ac H -Me -CONH ₂ H 5-56 -Ac H -Me -CONHMe H 5-57 -Ac H -Me -CON (Me) ₂ H 5-58 -Ac H -Me -CONHBu H 5-59 -Ac H -Me -CON (Bu) ₂ H 5-60 -Ac H -Me -CO-Pyrd (1 ) H 5-61 -Ac H -Me -CO ₂ HH 5-62 -Ac H -Me -CO ₂ Me H 5-63 -Ac H -Me -CO ₂ Et H 5-64 -Ac H -Me -CO ₂ Bz H 5-65 -Ac H -iBu -CO ₂ HH 5-66 -Ac H -iBu -CO ₂ Me H 5-67 -Ac H -Bz -CO ₂ HH 5-68 -Ac H -Bz -CO ₂ Me H 5-69 -Ac H -CH ₂ OtBu -CO ₂ HH 5-70 -Ac H -CH ₂ OtBu -CO ₂ Me H 5-71 -Ac H -CH ₂ CO ₂ tBu -CO ₂ HH 5- 72 -Ac H -CH ₂ CO ₂ tBu -CO ₂ Me H 5-73 -CO ₂ tBu H -H -CONH ₂ H 5-74 -CO ₂ tBu H -H -CONHMe H 5-75 -CO ₂ tBu H -H -CON (Me) ₂ H 5-76 -CO ₂ tBu H -H -CONHBu H 5-77 -CO ₂ tBu H -H -CON (Bu ) ₂ H 5-78 -CO ₂ tBu H -H -CO-Pyrd (1) H 5-79 -CO ₂ tBu H -H -CO ₂ HH 5-80 -CO ₂ tBu H -H -CO ₂ Me H 5-81 -CO ₂ tBu H -H -CO ₂ Et H 5-82 -CO ₂ tBu H -H -CO ₂ Bz H 5-83 -CO ₂ tBu H -Me -CONH ₂ H 5-84 -CO _{2 tBu H -Me -CONHMe H 5-85 -CO 2} tBu H -Me -CON (Me) 2 H 5-86 -CO 2 tBu H -Me -CONHEt H 5-87 -CO 2 tBu H -Me -CONHBu H 5-88 -CO ₂ tBu H -Me -CON (Bu) ₂ H 5-89 -CO ₂ tBu H -Me -CO-Pyrd (1) H 5-90 -CO ₂ tBu H -Me -CO-Pip ( 1) H 5-91 -CO ₂ tBu H -Me -CONHPh H 5-92 -CO ₂ tBu H -Me -CONH (2-CO ₂ H-Ph) H 5-93 -CO ₂ tBu H -Me -CONH (2-CO ₂ Me-Ph) H 5-94 -CO ₂ tBu H -Me -CONH (2-CO ₂ Et-Ph) H 5-95 -CO ₂ tBu H -Me -CONH (3-CO ₂ H -Ph) H 5-96 -CO ₂ tBu H -Me -CONH (3-CO ₂ Me-Ph) H 5-97 -CO ₂ tBu H -Me -CONH (3-CO ₂ Et-Ph) H 5- 98 -CO ₂ tBu H -Me -CONH (4-CO ₂ H-Ph) H 5-99 -CO ₂ tBu H -Me -CONH (4-CO ₂ Me-Ph) H 5-100 -CO ₂ tBu H -Me -CONH (4-CO ₂ Et-Ph) H 5-101 -CO ₂ tBu H -Me -CONHBz H 5-102 -CO ₂ tBu H -Me -C O ₂ HH 5-103 -CO ₂ tBu H -Me -CO ₂ Me H 5-104 -CO ₂ tBu H -Me -CO ₂ Et H 5-105 -CO ₂ tBu H -Me -CO ₂ Bz H 5- 106 -CO ₂ tBu H -Me -CO2 (2-OH-Bz) H 5-107 -CO ₂ tBu H -Me -CO2 (2-OMe-Bz) H 5-108 -CO ₂ tBu H -Me -CO2 (3-OH-Bz) H 5-109 -CO ₂ tBu H -Me -CO2 (3-OMe-Bz) H 5-110 -CO ₂ tBu H -Me -CO2 (4-OH-Bz) H 5- 111 -CO ₂ tBu H -Me -CO2 (4-OMe-Bz) H 5-112 -CO ₂ tBu H -Me -CO ₂ H 2-OH 5-113 -CO ₂ tBu H -Me -CO ₂ H 2 -Me 5-114 -CO ₂ tBu H -Me -CO ₂ H 2-OMe 5-115 -CO ₂ tBu H -Me -CO ₂ H 5-OH 5-116 -CO ₂ tBu H -Me -CO ₂ H 5-Me 5-117 -CO ₂ tBu H -Me -CO ₂ H 5-OMe 5-118 -CO ₂ tBu H -Me -CO ₂ H 2-Me 5-Me 5-119 -CO ₂ tBu H -Me -CO ₂ H 2-OH 5-Me 5-120 -CO ₂ tBu H -Me -CO ₂ H 2-OMe 5-Me 5-121 -CO ₂ tBu H -Me -CO ₂ Me 2-OH 5-122 -CO ₂ tBu H -Me -CO ₂ Me 2-Me 5-123 -CO ₂ tBu H -Me -CO ₂ Me 2-OMe 5-124 -CO ₂ tBu H -Me -CO ₂ Me 5-OH 5- 125 -CO ₂ tBu H -Me -CO ₂ Me 5-Me 5-126 -CO ₂ tBu H -Me -CO ₂ Me 5-OMe 5-127 -CO ₂ tBu H -Me -CO ₂ Me 2-Me 5 -Me 5-128 -CO ₂ tBu H -Me -CO ₂ Me 2-OH 5-Me 5-129 -CO ₂ tBu H -Me -CO ₂ Me 2-OMe 5-Me 5-130 -CO 2 tBu Me -Me -CONHMe H 5-131 -CO 2 tBu Me -Me -CONHBu H 5-132 -CO 2 tBu Me -Me -CON (Me) 2 H 5 _{-134 -CO 2 tBu Me -Me -CON (} Bu) 2 H 5-135 -CO 2 tBu Me -Me -CO-Pyrd (1) H 5-136 -CO 2 tBu Me -Me -CONH (2-CO ₂ Me-Ph) H 5-137 -CO ₂ tBu Me -Me -CONH (3-CO ₂ Et-Ph) H 5-138 -CO ₂ tBu Me -Me -CONH (4-CO ₂ Me-Ph) H 5-139 -CO ₂ tBu Me -Me -CO ₂ HH 5-140 -CO ₂ tBu Me -Me -CO ₂ Me H 5-141 -CO ₂ tBu Me -Me -CO ₂ Bz H 5-142 -CO ₂ tBu Me -Me -CO2 (4-OMe-Bz) H 5-143 -CO ₂ tBu H -Et -CO ₂ Me H 5-144 -CO ₂ tBu H -Pr -CO ₂ Me H 5-145 -CO ₂ tBu H -iPr -CONH ₂ H 5-146 -CO ₂ tBu H -iPr -CONHMe H 5-147 -CO ₂ tBu H -iPr -CON (Me) ₂ H 5-148 -CO ₂ tBu H -iPr -CONHBu H 5-149 -CO ₂ tBu H -iPr -CON (Bu) ₂ H 5-150 -CO ₂ tBu H -iPr -CO-Pyrd (1) H 5-151 -CO ₂ tBu H -iPr -CO ₂ HH 5-152 -CO ₂ tBu H -iPr -CO ₂ Me H 5-153 -CO ₂ tBu H -iPr -CO ₂ Et H 5-154 -CO ₂ tBu H -iPr -CO ₂ Bz H 5-155 -CO _{2 tBu H -Bu -CO 2 Me H} 5-156 -CO 2 tBu H -iBu -CONH 2 H 5-157 -CO 2 tBu H -iBu -CONHMe H 5-158 -CO 2 tBu H -iBu -CON ( Me) ₂ H 5-159 -CO ₂ tBu H -iBu -CONHBu H 5-160 -CO ₂ tBu H -iBu -CON (Bu) ₂ H 5-161 -CO ₂ tBu H -iBu -CO-Pyrd (1) H 5-162 -CO ₂ tBu H -iBu -CONH (2-CO ₂ Me-Ph) H 5-163 -CO ₂ tBu H -iBu -CONH (3-CO ₂ H-Ph) H 5-164 -CO ₂ tBu H -iBu -CONH (3-CO ₂ Me-Ph) H 5-165 -CO ₂ tBu H -iBu -CONH (4-CO ₂ H-Ph) H 5-166 -CO ₂ tBu H -iBu -CONH (4-CO ₂ Me-Ph) H 5-167 -CO ₂ tBu H -iBu -CO ₂ HH 5-168 -CO ₂ tBu H -iBu -CO ₂ Me H 5-169 -CO ₂ tBu H -iBu- CO ₂ Et H 5-170 -CO ₂ tBu H -iBu -CO ₂ Bz H 5-171 -CO ₂ tBu H -iBu -CO ₂ H 2-Me 5-172 -CO ₂ tBu H -iBu -CO ₂ H 2-Me 5-Me 5-173 -CO ₂ tBu H -iBu -CO ₂ H 2-OMe 5-Me 5-174 -CO ₂ tBu H -iBu -CO ₂ Me 2-Me 5-175 -CO ₂ tBu H -iBu -CO ₂ Me 2-Me 5-Me 5-176 -CO ₂ tBu H -iBu -CO ₂ Me 2-OMe 5-Me 5-177 -CO ₂ tBu Me -iBu -CONHMe H 5-178- CO ₂ tBu Me -iBu -CONHBu H 5-179 -CO ₂ tBu Me -iBu -CON (Me) ₂ H 5-180 -CO ₂ tBu Me -iBu -CON (Bu) ₂ H 5-181 -CO ₂ tBu Me -iBu -CO ₂ HH 5-182 -CO ₂ tBu Me -iBu -CO ₂ Me H 5-183 -CO ₂ tBu H -Ph -CONH ₂ H 5-184 -CO ₂ tBu H -Ph -CONHMe H 5 -185 -CO ₂ tBu H _{-Ph -CON (Me) 2 H 5-186} -CO 2 tBu H -Ph -CONHBu H 5-187 -CO 2 tBu H -Ph -CON (Bu) 2 H 5-188 -CO 2 tBu H -Ph - CO-Pyrd (1) H 5-189 -CO ₂ tBu H -Ph -CO ₂ HH 5-190 -CO ₂ tBu H -Ph -CO ₂ Me H 5-191 -CO ₂ tBu H -Ph -CO ₂ Et H 5-192 -CO ₂ tBu H -Ph -CO ₂ Bz H 5-193 -CO ₂ tBu H -Bz -CONH ₂ H 5-194 -CO ₂ tBu H -Bz -CONHMe H 5-195 -CO ₂ tBu H -Bz -CON (Me) ₂ H 5-196 -CO ₂ tBu H -Bz -CONHBu H 5-197 -CO ₂ tBu H -Bz -CON (Bu) ₂ H 5-198 -CO ₂ tBu H -Bz -CO-Pyrd (1) H 5-199 -CO ₂ tBu H -Bz -CONH (2-CO ₂ Me-Ph) H 5-200 -CO ₂ tBu H -Bz -CONH (3-CO ₂ H-Ph ) H 5-201 -CO ₂ tBu H -Bz -CONH (3-CO ₂ Me-Ph) H 5-202 -CO ₂ tBu H -Bz -CONH (4-CO ₂ H-Ph) H 5-203- CO ₂ tBu H -Bz -CONH (4-CO ₂ Me-Ph) H 5-204 -CO ₂ tBu H -Bz -CO ₂ HH 5-205 -CO ₂ tBu H -Bz -CO ₂ Me H 5-206 -CO ₂ tBu H -Bz -CO ₂ Et H 5-207 -CO ₂ tBu H -Bz -CO ₂ Bz H 5-208 -CO ₂ tBu H -Bz -CO ₂ H 2-Me 5-209 -CO ₂ tBu H -Bz -CO ₂ H 2-Me 5-Me 5-210 -CO ₂ tBu H -Bz -CO ₂ H 2-OMe 5-Me 5-211 -CO ₂ tBu H -Bz -CO ₂ Me 2- Me 5-212 -CO ₂ tBu H -Bz -CO ₂ Me 2-Me 5-Me 5-213 -CO ₂ tBu H -Bz -CO ₂ Me 2-OMe 5-Me 5-214 -CO ₂ tBu Me -Bz -CONHMe H 5-215 -CO ₂ tBu Me -Bz -CONHBu H 5-216 -CO ₂ tBu Me -Bz -CON (Me) ₂ H 5-217 -CO ₂ tBu Me -Bz -CON (Bu) ₂ H 5-218 -CO ₂ tBu Me -Bz -CO ₂ HH 5-219 -CO ₂ tBu Me- Bz -CO ₂ Me H 5-220 -CO ₂ tBu H -CH ₂ -Ind (3) -CONH ₂ H 5-221 -CO ₂ tBu H -CH ₂ -Ind (3) -CONHMe H 5-222 -CO ₂ tBu H -CH ₂ -Ind (3) -CON (Me) ₂ H 5-223 -CO ₂ tBu H -CH ₂ -Ind (3) -CONHBu H 5-224 -CO ₂ tBu H -CH ₂ -Ind (3) -CON (Bu) ₂ H 5-225 -CO ₂ tBu H -CH ₂ -Ind (3) -CO-Pyrd (1) H 5-226 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ HH 5-227 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Me H 5-228 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Et H 5-229- CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Bz H 5-230 -CO ₂ tBu H -CH ₂ OH -CO ₂ Me H 5-231 -CO ₂ tBu H -CH ₂ OMe -CO ₂ Me H 5-232 -CO ₂ tBu H -CH ₂ OtBu -CONH ₂ H 5-233 -CO ₂ tBu H -CH ₂ OtBu -CONHMe H 5-234 -CO ₂ tBu H -CH ₂ OtBu -CON (Me) ₂ H 5-235 -CO ₂ tBu H -CH ₂ OtBu -CONHBu H 5-236 -CO ₂ tBu H -CH ₂ OtBu -CON (Bu) ₂ H 5-237 -CO ₂ tBu H -CH ₂ OtBu -CO- Pyrd (1) H 5-238- CO ₂ tBu H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 5-239 -CO ₂ tBu H -CH ₂ OtBu -CONH (3-CO ₂ H-Ph) H 5-240 -CO ₂ tBu H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 5-241 -CO ₂ tBu H -CH ₂ OtBu -CONH (4-CO ₂ H-Ph) H 5-242 -CO ₂ tBu H -CH ₂ OtBu -CONH (4-CO ₂ Me-Ph) H 5-243 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ HH 5-244 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me H 5 -245 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Et H 5-246 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Bz H 5-247 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2 -Me 5-248 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-Me 5-Me 5-249 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-OMe 5-Me 5-250- CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-Me 5-251 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-Me 5-Me 5-252 -CO ₂ tBu H -CH ₂ OtBu- CO ₂ Me 2-OMe 5-Me 5-253 -CO ₂ tBu Me -CH ₂ OtBu -CONHMe H 5-254 -CO ₂ tBu Me -CH ₂ OtBu -CONHBu H 5-255 -CO ₂ tBu Me -CH ₂ OtBu -CON (Me) ₂ H 5-256 -CO ₂ tBu Me -CH ₂ OtBu -CON (Bu) ₂ H 5-257 -CO ₂ tBu Me -CH ₂ OtBu -CO ₂ HH 5-258 -CO ₂ tBu Me -CH ₂ OtBu -CO ₂ Me H 5-259 -CO ₂ tBu H -CH (Me) OH -CO ₂ Me H 5-260 -CO ₂ tBu H -CH (Me) OtBu -CON H ₂ H 5-261 -CO ₂ tBu H -CH (Me) OtBu -CONHMe H 5-262 -CO ₂ tBu H -CH (Me) OtBu -CON (Me) ₂ H 5-263 -CO ₂ tBu H- CH (Me) OtBu -CONHBu H 5-264 -CO ₂ tBu H -CH (Me) OtBu -CON (Bu) ₂ H 5-265 -CO ₂ tBu H -CH (Me) OtBu -CO-Pyrd (1) H 5-266 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ HH 5-267 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Me H 5-268 -CO ₂ tBu H -CH (Me ) OtBu -CO ₂ Et H 5-269 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Bz H 5-270 -CO ₂ tBu H -CH ₂ SMe -CO ₂ Me H 5-271 -CO ₂ tBu _{H - (CH 2) 2 SMe} -CONH 2 H 5-272 -CO 2 tBu H - (CH 2) 2 SMe -CONHMe H 5-273 -CO 2 tBu H - (CH 2) 2 SMe -CON (Me) ₂ H 5-274 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CONHBu H 5-275 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CON (Bu) ₂ H 5-276 -CO ₂ tBu H -(CH ₂ ) ₂ SMe -CO-Pyrd (1) H 5-277 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ HH 5-278 -CO ₂ tBu H-(CH ₂ ) ₂ SMe- CO ₂ Me H 5-279 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Et H 5-280 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Bz H 5-281 -CO ₂ tBu H -CH ₂ CO ₂ H -CO ₂ Me H 5-282 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ H -CO ₂ Me H 5-283 -CO ₂ tBu H -CH ₂ CO ₂ tBu- CONH ₂ H 5-284 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHMe H 5-285 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 5-286 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHBu H 5-287 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 5-288 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 5-289 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 5-290 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ H-Ph) H 5-291 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 5-292 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ H-Ph) H 5-293 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 5-294 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ HH 5-295 -CO ₂ tBu H- CH ₂ CO ₂ tBu -CO ₂ Me H 5-296 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Et H 5-297 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Bz H 5- 298 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-299 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-Me 5-300 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-OMe 5-Me 5-301 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 5-302 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 5-Me 5-303 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-OMe 5-Me 5-304 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -C ONHMe H 5-305 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CONHBu H 5-306 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CON (Me) ₂ H 5-307 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 5-308 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CO ₂ HH 5-309 -CO ₂ tBu Me -CH ₂ CO ₂ tBu -CO ₂ Me H 5- 310 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 5-311 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 5-312 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 5-313 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CONHBu H 5-314 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CON (Bu) ₂ H 5-315 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO-Pyrd (1) H 5-316 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu- CO ₂ HH 5-317 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 5-318 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 5-319 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Bz H 5-320 -CO ₂ tBu H -CH ₂ NH ₂ -CO ₂ Me H 5-321 -CO ₂ tBu H-(CH ₂ ) ₂ NH ₂ -CO ₂ Me H 5-322 -CO ₂ tBu H -CH ₂ NHCO ₂ tBu -CO ₂ Me H 5-323 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ tBu -CO ₂ Me H 5 -324 -CO ₂ tBu H-(CH ₂ ) ₂ NHCO ₂ Bz -CO ₂ Me H 5-325 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO NH ₂ H 5-326 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 5-327 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 5-328 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHBu H 5-329 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Bu) ₂ H 5-330 -CO ₂ tBu H- (CH ₂ ) ₄ NHCO ₂ Bz -CO-Pyrd (1) H 5-331 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 5-332 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 5-333 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 5-334 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Bz H 5-335 -CO ₂ tBu H -CH ₂ (4-OH-Ph) -CO ₂ Me H 5-336 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONH ₂ H 5- 337 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONHMe H 5-338 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 5-339 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONHBu H 5-340 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CON (Bu) ₂ H 5-341 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO-Pyrd (1) H 5-342 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ HH 5-343 -CO ₂ tBu H -CH ₂ ( 4-BzO-Ph) -CO ₂ Me H 5-344 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 5-345 -CO ₂ tBu H -CH ₂ (4-BzO- Ph) -CO ₂ Bz H 5-346 -CO ₂ Bz H -H -CONH ₂ H 5-3 47 -CO ₂ Bz H -H -CONHMe H 5-348 -CO ₂ Bz H -H -CON (Me) ₂ H 5-349 -CO ₂ Bz H -H -CONHBu H 5-350 -CO ₂ Bz H- H -CON (Bu) ₂ H 5-351 -CO ₂ Bz H -H -CO-Pyrd (1) H 5-352 -CO ₂ Bz H -H -CO ₂ HH 5-353 -CO ₂ Bz H -H -CO ₂ Me H 5-354 -CO ₂ Bz H -H -CO ₂ Et H 5-355 -CO ₂ Bz H -H -CO ₂ Bz H 5-356 -CO ₂ Bz H -Me -CONH ₂ H 5 -357 -CO ₂ Bz H -Me -CONHMe H 5-358 -CO ₂ Bz H -Me -CON (Me) ₂ H 5-359 -CO ₂ Bz H -Me -CONHEt H 5-360 -CO ₂ Bz H -Me -CONHBu H 5-361 -CO ₂ Bz H -Me -CON (Bu) ₂ H 5-362 -CO ₂ Bz H -Me -CO-Pyrd (1) H 5-363 -CO ₂ Bz H -Me -CO-Pip (1) H 5-364 -CO ₂ Bz H -Me -CONHPh H 5-365 -CO ₂ Bz H -Me -CONH (2-CO ₂ H-Ph) H 5-366 -CO ₂ Bz H -Me -CONH (2-CO ₂ Me-Ph) H 5-367 -CO ₂ Bz H -Me -CONH (2-CO ₂ Et-Ph) H 5-368 -CO ₂ Bz H -Me -CONH ( 3-CO ₂ H-Ph) H 5-369 -CO ₂ Bz H -Me -CONH (3-CO ₂ Me-Ph) H 5-370 -CO ₂ Bz H -Me -CONH (3-CO ₂ Et- Ph) H 5-371 -CO ₂ Bz H -Me -CONH (4-CO ₂ H-Ph) H 5-372 -CO ₂ Bz H -Me -CONH (4-CO ₂ Me-Ph) H 5-373 -CO ₂ Bz H -Me -CONH (4-CO ₂ Et-Ph) H 5-374 -CO ₂ Bz H -Me -CONHBz H 5-375 -CO ₂ Bz H -Me -CO ₂ HH 5-376 -CO ₂ Bz H -Me -CO ₂ Me H 5-377 -CO ₂ Bz H -Me -CO ₂ Et H 5-378 -CO ₂ Bz H -Me -CO ₂ Bz H 5-379 -CO ₂ Bz H -Me -CO2 (2-OH-Bz) H 5-380 -CO ₂ Bz H -Me -CO2 (2-OMe-Bz) H 5-381 -CO ₂ Bz H -Me -CO2 (3-OH-Bz) H 5-382 -CO ₂ Bz H -Me -CO2 (3-OMe-Bz) H 5-383 -CO ₂ Bz H -Me -CO2 (4-OH-Bz ) H 5-384 -CO ₂ Bz H -Me -CO2 (4-OMe-Bz) H 5-385 -CO ₂ Bz H -Me -CO ₂ H 2-OH 5-386 -CO ₂ Bz H -Me- CO ₂ H 2-Me 5-387 -CO ₂ Bz H -Me -CO ₂ H 2-OMe 5-388 -CO ₂ Bz H -Me -CO ₂ H 5-OH 5-389 -CO ₂ Bz H -Me -CO ₂ H 5-Me 5-390 -CO ₂ Bz H -Me -CO ₂ H 5-OMe 5-391 -CO ₂ Bz H -Me -CO ₂ H 2-Me 5-Me 5-392 -CO ₂ Bz H -Me -CO ₂ H 2-OH 5-Me 5-393 -CO ₂ Bz H -Me -CO ₂ H 2-OMe 5-Me 5-394 -CO ₂ Bz H -Me -CO ₂ Me 2- OH 5-395 -CO ₂ Bz H -Me -CO ₂ Me 2-Me 5-396 -CO ₂ Bz H -Me -CO ₂ Me 2-OMe 5-397 -CO ₂ Bz H -Me -CO ₂ Me 5 -OH 5-398 -CO ₂ Bz H -Me -CO ₂ Me 5-Me 5-399 -CO ₂ Bz H -Me -CO ₂ Me 5-OMe 5-400 -CO ₂ Bz H -Me -CO ₂ Me 2-Me 5-Me 5-401 -CO ₂ Bz H -Me -CO ₂ Me 2-OH 5-Me 5-402 -CO ₂ Bz H -Me -CO ₂ Me 2-OMe 5-Me 5-403 -CO ₂ Bz Me -Me -CONHMe H 5-404 -CO ₂ Bz Me -Me -CONHBu H 5-405 -CO ₂ Bz Me -Me -CON (Me) ₂ H 5-406 -CO ₂ Bz Me -Me -CON (Bu) ₂ H 5-407 -CO ₂ Bz Me -Me -CO-Pyrd (1) H 5-408 -CO ₂ Bz Me -Me -CONH (2-CO ₂ Me-Ph) H 5-409 -CO ₂ Bz Me -Me -CONH (3-CO ₂ Et-Ph) H 5-400 -CO ₂ Bz Me -Me -CONH (4-CO ₂ Me-Ph) H 5-411 -CO ₂ Bz Me- Me -CO ₂ HH 5-412 -CO ₂ Bz Me -Me -CO ₂ Me H 5-413 -CO ₂ Bz Me -Me -CO ₂ Bz H 5-414 -CO ₂ Bz Me -Me -CO2 (4- OMe-Bz) H 5-415 -CO ₂ Bz H -Et -CO ₂ Me H 5-416 -CO ₂ Bz H -Pr -CO ₂ Me H 5-417 -CO ₂ Bz H -iPr -CONH ₂ H 5 -418 -CO ₂ Bz H -iPr -CONHMe H 5-419 -CO ₂ Bz H -iPr -CON (Me) ₂ H 5-420 -CO ₂ Bz H -iPr -CONHBu H 5-421 -CO ₂ Bz H -iPr -CON (Bu) ₂ H 5-422 -CO ₂ Bz H -iPr -CO-Pyrd (1) H 5-423 -CO ₂ Bz H -iPr -CO ₂ HH 5-424 -CO ₂ Bz H- iPr -CO ₂ Me H 5-425 -CO ₂ Bz H -iPr -CO ₂ Et H 5-426 -CO ₂ Bz H -iPr -CO ₂ Bz H 5-427 -CO ₂ Bz H -Bu -CO ₂ Me H 5-428 -CO ₂ Bz H -iBu -CONH ₂ H 5-429 -CO ₂ Bz H -iBu -CONHMe H 5-430 -CO ₂ Bz H -iBu -CON (Me) ₂ H 5-431 -CO ₂ Bz H -iBu -CONHBu H 5-432 -CO ₂ Bz H -iBu -CON (Bu) ₂ H 5-433 -CO ₂ Bz H -iBu -CO-Pyrd (1) H 5-434 -CO ₂ Bz H -iBu -CONH (2-CO ₂ Me-Ph ) H 5-435 -CO ₂ Bz H -iBu -CONH (3-CO ₂ H-Ph) H 5-436 -CO ₂ Bz H -iBu -CONH (3-CO ₂ Me-Ph) H 5-437- CO ₂ Bz H -iBu -CONH (4-CO ₂ H-Ph) H 5-438 -CO ₂ Bz H -iBu -CONH (4-CO ₂ Me-Ph) H 5-439 -CO ₂ Bz H -iBu -CO ₂ HH 5-440 -CO ₂ Bz H -iBu -CO ₂ Me H 5-441 -CO ₂ Bz H -iBu -CO ₂ Et H 5-442 -CO ₂ Bz H -iBu -CO ₂ Bz H 5 -443 -CO ₂ Bz H -iBu -CO ₂ H 2-Me 5-444 -CO ₂ Bz H -iBu -CO ₂ H 2-Me 5-Me 5-445 -CO ₂ Bz H -iBu -CO ₂ H 2-OMe 5-Me 5-446 -CO ₂ Bz H -iBu -CO ₂ Me 2-Me 5-447 -CO ₂ Bz H -iBu -CO ₂ Me 2-Me 5-Me 5-448 -CO ₂ Bz H -iBu -CO ₂ Me 2-OMe 5-Me 5-449 -CO ₂ Bz Me -iBu -CONHMe H 5-450 -CO ₂ Bz Me -iBu -CONHBu H 5-451 -CO ₂ Bz Me -iBu- CON (Me) ₂ H 5-452 -CO ₂ Bz Me -iBu -CON (Bu) ₂ H 5-453 -CO ₂ Bz Me -iBu -CO ₂ HH 5-454 -CO ₂ Bz Me -iBu -CO ₂ Me H 5-455 -CO ₂ Bz H -Ph -CONH ₂ H 5-456 -CO ₂ Bz H -Ph -CONHMe H 5-457 -CO ₂ Bz H -Ph -CON (Me) ₂ H 5-458- CO ₂ Bz H -Ph -CONHBu H 5-459 -CO ₂ Bz H -Ph -CO N (Bu) ₂ H 5-460 -CO ₂ Bz H -Ph -CO-Pyrd (1) H 5-461 -CO ₂ Bz H -Ph -CO ₂ HH 5-462 -CO ₂ Bz H -Ph -CO ₂ Me H 5-463 -CO ₂ Bz H -Ph -CO ₂ Et H 5-464 -CO ₂ Bz H -Ph -CO ₂ Bz H 5-465 -CO ₂ Bz H -Bz -CONH ₂ H 5-466 -CO ₂ Bz H -Bz -CONHMe H 5-467 -CO ₂ Bz H -Bz -CON (Me) ₂ H 5-468 -CO ₂ Bz H -Bz -CONHBu H 5-469 -CO ₂ Bz H -Bz -CON (Bu) ₂ H 5-470 -CO ₂ Bz H -Bz -CO-Pyrd (1) H 5-471 -CO ₂ Bz H -Bz -CONH (2-CO ₂ Me-Ph) H 5-472 -CO ₂ Bz H -Bz -CONH (3-CO ₂ H-Ph) H 5-473 -CO ₂ Bz H -Bz -CONH (3-CO ₂ Me-Ph) H 5-474 -CO ₂ Bz H- Bz -CONH (4-CO ₂ H-Ph) H 5-475 -CO ₂ Bz H -Bz -CONH (4-CO ₂ Me-Ph) H 5-476 -CO ₂ Bz H -Bz -CO ₂ HH 5 -477 -CO ₂ Bz H -Bz -CO ₂ Me H 5-478 -CO ₂ Bz H -Bz -CO ₂ Et H 5-479 -CO ₂ Bz H -Bz -CO ₂ Bz H 5-480 -CO ₂ Bz H -Bz -CO ₂ H 2-Me 5-481 -CO ₂ Bz H -Bz -CO ₂ H 2-Me 5-Me 5-482 -CO ₂ Bz H -Bz -CO ₂ H 2-OMe 5- Me 5-483 -CO ₂ Bz H -Bz -CO ₂ Me 2-Me 5-484 -CO ₂ Bz H -Bz -CO ₂ Me 2-Me 5-Me 5-485 -CO ₂ Bz H -Bz -CO ₂ Me 2-OMe 5-Me 5-486 -CO ₂ Bz Me -Bz -CONHMe H 5-487 -CO ₂ Bz Me -Bz -CONHBu H 5 -488 -CO ₂ Bz Me -Bz -CON (Me) ₂ H 5-489 -CO ₂ Bz Me -Bz -CON (Bu) ₂ H 5-490 -CO ₂ Bz Me -Bz -CO ₂ HH 5-491 -CO ₂ Bz Me -Bz -CO ₂ Me H 5-492 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CONH ₂ H 5-493 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CONHMe H 5-494 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CON (Me) ₂ H 5- 495 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CONHBu H 5-496 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)]- CON (Bu) ₂ H 5-497 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CO-Pyrd (1) H 5-498 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CO ₂ HH 5-499 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CO ₂ Me H 5-500 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CO ₂ Et H 5-501 -CO ₂ Bz H -CH _2- [1-CO ₂ Me-Ind (3)] -CO ₂ Bz H 5-502 -CO ₂ Bz H -CH ₂ OH -CO ₂ Me H 5-503 -CO ₂ Bz H -CH ₂ OMe -CO ₂ Me H 5-504 -CO ₂ Bz H -CH ₂ OtBu- CONH ₂ H 5-505 -CO ₂ Bz H -CH ₂ OtBu -CONHMe H 5-506 -CO ₂ Bz H -CH ₂ OtBu -CON (Me) ₂ H 5-507 -CO ₂ Bz H -CH ₂ OtBu- CONHBu H 5-508 -CO ₂ Bz H -CH ₂ OtBu -CON (Bu) ₂ H 5-509 -CO ₂ Bz H -CH ₂ OtBu -CO-Pyrd (1) H 5-510 -CO ₂ Bz H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 5-511 -CO ₂ Bz H -CH ₂ OtBu -CONH (3-CO ₂ H-Ph) H 5-512 -CO ₂ Bz H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 5-513 -CO ₂ Bz H -CH ₂ OtBu -CONH (4-CO ₂ H-Ph) H 5-514 -CO ₂ Bz H -CH ₂ OtBu -CONH (4-CO ₂ Me-Ph) H 5-515 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ HH 5-516 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me H 5-517 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Et H 5-508 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Bz H 5-519 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-Me 5-520 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-Me 5-Me 5-521 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-OMe 5-Me 5-522 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-Me 5-523 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-Me 5-Me 5-524 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-OMe 5-Me 5-525 -CO ₂ Bz Me -CH ₂ OtBu -CONHMe H 5-526 -CO ₂ Bz Me -CH ₂ OtBu -CONHBu H 5-527 -CO ₂ Bz Me -CH ₂ OtBu- CON (Me) ₂ H 5-528 -CO ₂ Bz Me -CH ₂ OtBu -CON (Bu) ₂ H 5-529 -CO ₂ Bz Me -CH ₂ OtBu -CO ₂ HH 5-530 -CO ₂ Bz Me- CH ₂ OtBu -CO ₂ Me H 5-531 -CO ₂ Bz H -CH (Me) OH -CO ₂ Me H 5-532 -CO ₂ Bz H -CH (Me) OtBu -CONH ₂ H 5-533 -CO ₂ Bz H -CH (M e) OtBu -CONHMe H 5-534 -CO ₂ Bz H -CH (Me) OtBu -CON (Me) ₂ H 5-535 -CO ₂ Bz H -CH (Me) OtBu -CONHBu H 5-536 -CO ₂ Bz H -CH (Me) OtBu -CON (Bu) ₂ H 5-537 -CO ₂ Bz H -CH (Me) OtBu -CO-Pyrd (1) H 5-538 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ HH 5-539 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Me H 5-540 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Et H 5-541 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Bz H 5-542 -CO ₂ Bz H -CH ₂ SMe -CO ₂ Me H 5-543 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONH ₂ H 5- 544 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONHMe H 5-545 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 5-546 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONHBu H 5-547 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CON (Bu) ₂ H 5-548 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO-Pyrd (1) H 5-549 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ HH 5-550 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Me H 5-551 -CO ₂ Bz H-( CH ₂ ) ₂ SMe -CO ₂ Et H 5-552 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Bz H 5-553 -CO ₂ Bz H -CH ₂ CO ₂ H -CO ₂ Me H 5 -554 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ H -CO ₂ Me H 5-555 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH ₂ H 5-556 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHMe H 5-557 -CO ₂ Bz H- CH ₂ CO ₂ tBu -CON (Me) ₂ H 5-558 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHBu H 5-559 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 5-560 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 5-561 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 5- 562 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ H-Ph) H 5-563 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 5-564 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ H-Ph) H 5-565 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph ) H 5-566 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ HH 5-567 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me H 5-568 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Et H 5-569 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Bz H 5-570 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5- 571 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-Me 5-572 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-OMe 5-Me 5-573- CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 5-574 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 5-Me 5-575 -CO ₂ Bz H- CH ₂ CO ₂ tBu -CO ₂ Me 2-OMe 5-Me 5-576 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CONHMe H 5-577 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CONHBu H 5 -578 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CON (Me) ₂ H 5-579 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 5-580 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CO ₂ HH 5-581 -CO ₂ Bz Me -CH ₂ CO ₂ tBu -CO ₂ Me H 5-582 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 5-583 -CO ₂ Bz H-( CH ₂ ) ₂ CO ₂ tBu -CONHMe H 5-584 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 5-585 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONHBu H 5-586 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CON (Bu) ₂ H 5-587 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO-Pyrd ( 1) H 5-588 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 5-589 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 5-590- CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 5-591 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Bz H 5-592 -CO ₂ Bz H -CH ₂ NH ₂ -CO ₂ Me H 5-593 -CO ₂ Bz H-(CH ₂ ) ₂ NH ₂ -CO ₂ Me H 5-594 -CO ₂ Bz H -CH ₂ NHCO ₂ tBu -CO ₂ Me H 5- 595 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ tBu -CO ₂ Me H 5-596 -CO ₂ Bz H-(CH ₂ ) ₂ NHCO ₂ Bz -CO ₂ Me H 5-597 -CO ₂ Bz H -(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 5-598 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 5-599 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 5-600 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHBu H 5-601 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Bu) ₂ H 5-602 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO-Pyrd (1) H 5-603 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 5-604 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 5-605 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 5-606 -CO ₂ Bz H- (CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Bz H 5-607 -CO ₂ Bz H -CH ₂ (4-OH-Ph) -CO ₂ Me H 5-608 -CO ₂ Bz H -CH ₂ (4- (BzO-Ph) -CONH ₂ H 5-609 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONHMe H 5-610 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CON ( Me) ₂ H 5-611 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONHBu H 5-612 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CON (Bu) ₂ H 5-613 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO-Pyrd (1) H 5-614 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ HH 5- 615 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 5-616 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 5-617 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Bz H . [Table 6]

[0060]

Embedded image Compd. R ¹ R ² R ^3a AR ⁵ 6-1 -HH -Me -CONH ₂ H 6-2 -HH -Me -CONHMe H 6-3 -HH -Me -CON (Me) ₂ H 6-4 -HH -Me -CO ₂ HH 6-5- HH -Me -CO ₂ Me H 6-6 -HH -Me -CO ₂ Et H 6-7 -HH -iBu -CO ₂ Me H 6-8 -HH -Bz -CO ₂ Me H 6-9 -HH- CH ₂ OtBu -CO ₂ Me H 6-10 -HH -CH ₂ CO ₂ tBu -CO ₂ Me H 6-11 -Me H -Me -CONH ₂ H 6-12 -Me H -Me -CONHMe H 6-13 -Me H -Me -CON (Me) ₂ H 6-14 -Me H -Me -CO ₂ HH 6-15 -Me H -Me -CO ₂ Me H 6-16 -Me H -Me -CO ₂ Et H 6-17 -Me H -iBu -CO ₂ Me H 6-18 -Me H -Bz -CO ₂ Me H 6-19 -Me H -CH ₂ OtBu -CO ₂ Me H 6-20 -Me H -CH ₂ CO ₂ tBu -CO ₂ Me H 6-21 -Ph H -Me -CONH ₂ H 6-22 -Ph H -Me -CONHMe H 6-23 -Ph H -Me -CON (Me) ₂ H 6-24- Ph H -Me -CO ₂ HH 6-25 -Ph H -Me -CO ₂ Me H 6-26 -Ph H -Me -CO ₂ Et H 6-27 -Ph H -iBu -CO ₂ Me H 6-28 -Ph H -Bz -CO ₂ Me H 6-29 -Ph H -CH ₂ OtBu -CO ₂ Me H 6-30 -Ph H -CH ₂ CO ₂ tBu -CO ₂ Me H 6-31 -Ac H -Me -CONH ₂ H 6-32 -Ac H -Me -CONHMe H 6-33 -Ac H -Me -CON (Me) ₂ H 6-34 -Ac H -Me -CO ₂ HH 6-35 -Ac H -Me -CO ₂ Me H 6-36 -Ac H -Me -CO ₂ Et H 6-37 -Ac H -iBu -CO ₂ Me H 6-38 -Ac H -Bz -C O ₂ Me H 6-39 -Ac H -CH ₂ OtBu -CO ₂ Me H 6-40 -Ac H -CH ₂ CO ₂ tBu -CO ₂ Me H 6-41 -CO ₂ tBu H -H -CONH ₂ H 6-42 -CO ₂ tBu H -H -CONHMe H 6-43 -CO ₂ tBu H -H -CON (Me) ₂ H 6-44 -CO ₂ tBu H -H -CO ₂ HH 6-45 -CO ₂ tBu H -H -CO ₂ Me H 6-46 -CO ₂ tBu H -H -CO ₂ Et H 6-47 -CO ₂ tBu H -Me -CONH ₂ H 6-48 -CO ₂ tBu H -Me -CONHMe _{H 6-49 -CO 2 tBu H -Me -CON} (Me) 2 H 6-50 -CO 2 tBu H -Me -CONHBu H 6-51 -CO 2 tBu H -Me -CON (Bu) 2 H 6- 52 -CO ₂ tBu H -Me -CO-Pyrd (1) H 6-53 -CO ₂ tBu H -Me -CONH (2-CO ₂ Me-Ph) H 6-54 -CO ₂ tBu H -Me -CONH (3-CO ₂ H-Ph) H 6-55 -CO ₂ tBu H -Me -CONH (3-CO ₂ Me-Ph) H 6-56 -CO ₂ tBu H -Me -CONH (4-CO ₂ H -Ph) H 6-57 -CO ₂ tBu H -Me -CONH (4-CO ₂ Me-Ph) H 6-58 -CO ₂ tBu H -Me -CO ₂ HH 6-59 -CO ₂ tBu H -Me -CO ₂ Me H 6-60 -CO ₂ tBu H -Me -CO ₂ Et H 6-61 -CO ₂ tBu H -Me -CO ₂ Bz H 6-62 -CO ₂ tBu H -Me -CO ₂ H 2 -Me 6-63 -CO ₂ tBu H -Me -CO ₂ H 2-Me 5-Me 6-64 -CO ₂ tBu H -Me -CO ₂ H 2-OMe 5-Me 6-65 -CO ₂ tBu H -Me -CO ₂ Me 2-Me 6-66 -CO ₂ tBu H -Me -CO ₂ Me 2-Me 5-Me 6-67 -CO ₂ tBu H -Me -CO ₂ Me 2-OMe 5-Me 6-68 -CO ₂ tBu Me -Me -CONHMe H 6-69 -CO ₂ tBu Me -Me -CONHBu H 6-70 -CO ₂ tBu Me -Me- CON (Me) ₂ H 6-71 -CO ₂ tBu Me -Me -CON (Bu) ₂ H 6-72 -CO ₂ tBu Me -Me -CO ₂ HH 6-73 -CO ₂ tBu Me -Me -CO ₂ Me H 6-74 -CO ₂ tBu H -iPr -CONH ₂ H 6-75 -CO ₂ tBu H -iPr -CONHMe H 6-76 -CO ₂ tBu H -iPr -CON (Me) ₂ H 6-77- CO ₂ tBu H -iPr -CO ₂ HH 6-78 -CO ₂ tBu H -iPr -CO ₂ Me H 6-79 -CO ₂ tBu H -iPr -CO ₂ Et H 6-80 -CO ₂ tBu H -iBu -CONH ₂ H 6-81 -CO ₂ tBu H -iBu -CONHMe H 6-82 -CO ₂ tBu H -iBu -CON (Me) ₂ H 6-83 -CO ₂ tBu H -iBu -CONHBu H 6-84 -CO ₂ tBu H -iBu -CON (Bu) ₂ H 6-85 -CO ₂ tBu H -iBu -CO-Pyrd (1) H 6-86 -CO ₂ tBu H -iBu -CONH (2-CO ₂ Me -Ph) H 6-87 -CO ₂ tBu H -iBu -CONH (3-CO ₂ Me-Ph) H 6-88 -CO ₂ tBu H -iBu -CONH (4-CO ₂ Me-Ph) H 6- 89 -CO ₂ tBu H -iBu -CO ₂ HH 6-90 -CO ₂ tBu H -iBu -CO ₂ Me H 6-91 -CO ₂ tBu H -iBu -CO ₂ Et H 6-92 -CO ₂ tBu H -iBu -CO ₂ Bz H 6-93 -CO ₂ tBu H -iBu -CO ₂ H 2-Me 6-94 -CO ₂ tBu H -iBu -CO ₂ H 2-Me 5-Me 6-95 -CO ₂ tBu H -iBu -CO ₂ H 2-OMe 5-Me 6-96 -CO ₂ tBu H -iBu -CO ₂ Me 2-Me 6-97 -CO ₂ tBu H -iBu -CO ₂ Me 2-Me 5-Me 6-98 -CO ₂ tBu H -iBu -CO ₂ Me 2-OMe 5-Me 6-99 -CO ₂ tBu H -Ph -CONH ₂ H 6-100 -CO ₂ tBu H -Ph -CONHMe H 6-101 -CO ₂ tBu H -Ph -CON (Me) ₂ H 6-102 -CO ₂ tBu H -Ph -CO ₂ HH 6-103 -CO ₂ tBu H -Ph -CO ₂ Me H 6-104 -CO ₂ tBu H -Ph -CO ₂ Et H 6-105 -CO ₂ tBu H -Bz -CONH ₂ H 6-106 -CO ₂ tBu H -Bz -CONHMe H 6-107 -CO ₂ tBu H -Bz -CON (Me) ₂ H 6-108 -CO ₂ tBu H -Bz- CONHBu H 6-109 -CO ₂ tBu H -Bz -CON (Bu) ₂ H 6-110 -CO ₂ tBu H -Bz -CO-Pyrd (1) H 6-111 -CO ₂ tBu H -Bz -CONH ( 2-CO ₂ Me-Ph) H 6-112 -CO ₂ tBu H -Bz -CONH (3-CO ₂ Me-Ph) H 6-113 -CO ₂ tBu H -Bz -CONH (4-CO ₂ Me- _{Ph) H 6-114 -CO 2 tBu H} -Bz -CO 2 HH 6-115 -CO 2 tBu H -Bz -CO 2 Me H 6-116 -CO 2 tBu H -Bz -CO 2 Et H 6-117 -CO ₂ tBu H -Bz -CO ₂ Bz H 6-118 -CO ₂ tBu H -Bz -CO ₂ H 2-Me 6-119 -CO ₂ tBu H -Bz -CO ₂ H 2-Me 5-Me 6 -120 -CO ₂ tBu H -Bz -CO ₂ H 2-OMe 5-Me 6-121 -CO ₂ tBu H -Bz -CO ₂ Me 2-Me 6-122 -CO ₂ tBu H -Bz -CO ₂ Me 2-Me 5-Me 6-123 -CO ₂ tBu H -Bz -CO ₂ Me 2-OMe 5-Me 6-124 -CO ₂ tBu H -CH ₂ -Ind (3) -CONH ₂ H 6-125 -CO ₂ tBu H -CH ₂ -Ind (3) -CONHMe H 6-126- CO ₂ tBu H -CH ₂ -Ind (3) -CON (Me) ₂ H 6-127 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ HH 6-128 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Me H 6-129 -CO ₂ tBu H -CH ₂ -Ind (3) -CO ₂ Et H 6-130 -CO ₂ tBu H -CH ₂ OtBu -CONH ₂ H 6-131 -CO ₂ tBu H -CH ₂ OtBu -CONHMe H 6-132 -CO ₂ tBu H -CH ₂ OtBu -CON (Me) ₂ H 6-133 -CO ₂ tBu H -CH ₂ OtBu -CONHBu H 6-134- CO ₂ tBu H -CH ₂ OtBu -CON (Bu) ₂ H 6-135 -CO ₂ tBu H -CH ₂ OtBu -CO-Pyrd (1) H 6-136 -CO ₂ tBu H -CH ₂ OtBu -CONH ( 2-CO ₂ Me-Ph) H 6-137 -CO ₂ tBu H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 6-138 -CO ₂ tBu H -CH ₂ OtBu -CONH (4- (CO ₂ Me-Ph) H 6-139 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ HH 6-140 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me H 6-141 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Et H 6-142 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Bz H 6-143 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-Me 6-144 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-Me 5-Me 6-145 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ H 2-OMe 5-Me 6-146 -CO ₂ tBu H -CH ₂ OtBu- CO ₂ Me 2-Me 6-147 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-Me 5-Me 6-148 -CO ₂ tBu H -CH ₂ OtBu -CO ₂ Me 2-OMe 5-Me 6-149 -CO ₂ tBu H -CH (Me) OtBu -CONH ₂ H 6-150 -CO ₂ tBu H -CH (Me) OtBu -CONHMe H 6-151 -CO ₂ tBu H -CH (Me) OtBu -CON (Me ) ₂ H 6-152 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ HH 6-153 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Me H 6-154 -CO ₂ tBu H -CH (Me) OtBu -CO ₂ Et H 6-155 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CONH ₂ H 6-156 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CONHMe H 6-157- CO ₂ tBu H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 6-158 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ HH 6-159 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Me H 6-160 -CO ₂ tBu H-(CH ₂ ) ₂ SMe -CO ₂ Et H 6-161 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH ₂ H 6-162 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHMe H 6-163 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 6-164 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONHBu H 6-165 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 6-166 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 6-167 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 6-168 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 6-169 -CO ₂ tB u H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 6-170 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ HH 6-171 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me H 6-172 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Et H 6-173 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Bz H 6-174 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 6-175 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-Me 6-176 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ H 2-OMe 5-Me 6-177 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 6-178 -CO ₂ tBu H -CH ₂ CO ₂ tBu- CO ₂ Me 2-Me 5-Me 6-179 -CO ₂ tBu H -CH ₂ CO ₂ tBu -CO ₂ Me 2-OMe 5-Me 6-180 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu _{-CONH 2 H 6-181 -CO 2 tBu H} - (CH 2) 2 CO 2 tBu -CONHMe H 6-182 -CO 2 tBu H - (CH 2) 2 CO 2 tBu -CON (Me) 2 H 6- 183 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 6-184 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 6-185 -CO ₂ tBu H- (CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 6-186 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 6-187 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 6-188 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 6-189 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 6-190 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 6-191 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 6-192- CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONH ₂ H 6-193 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CONHMe H 6-194 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 6-195 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ HH 6-196 -CO ₂ tBu H -CH ₂ (4- (BzO-Ph) -CO ₂ Me H 6-197 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) -CO ₂ Et H 6-198 -CO ₂ Bz H -H -CONH ₂ H 6-199- CO ₂ Bz H -H -CONHMe H 6-200 -CO ₂ Bz H -H -CON (Me) ₂ H 6-201 -CO ₂ Bz H -H -CO ₂ HH 6-202 -CO ₂ Bz H -H -CO ₂ Me H 6-203 -CO ₂ Bz H -H -CO ₂ Et H 6-204 -CO ₂ Bz H -Me -CONH ₂ H 6-205 -CO ₂ Bz H -Me -CONHMe H 6-206 -CO ₂ Bz H -Me -CON (Me) ₂ H 6-207 -CO ₂ Bz H -Me -CONHBu H 6-208 -CO ₂ Bz H -Me -CON (Bu) ₂ H 6-209 -CO ₂ Bz H -Me -CO-Pyrd (1) H 6-210 -CO ₂ Bz H -Me -CONH (2-CO ₂ Me-Ph) H 6-211 -CO ₂ Bz H -Me -CONH (3-CO ₂ H-Ph) H 6-212 -CO ₂ Bz H -Me -CONH (3-CO ₂ Me-Ph) H 6-213 -CO ₂ Bz H -Me -CONH (4-CO ₂ H-Ph) H 6-214 -CO ₂ Bz H -Me -CONH (4-CO ₂ Me-Ph) H 6-215 -CO ₂ Bz H -Me -CO ₂ HH 6-216 -CO ₂ Bz H -Me -CO ₂ Me H 6-217 -CO ₂ Bz H -Me -CO ₂ Et H 6-218 -CO ₂ Bz H -Me -CO ₂ Bz H 6-219- CO ₂ Bz H -Me -CO ₂ H 2-Me 6-220 -CO ₂ Bz H -Me -CO ₂ H 2-Me 5-Me 6-221 -CO ₂ Bz H -Me -CO ₂ H 2-OMe 5-Me 6-222 -CO ₂ Bz H -Me -CO ₂ Me 2-Me 6-223 -CO ₂ Bz H -Me -CO ₂ Me 2-Me 5-Me 6-224 -CO ₂ Bz H -Me -CO ₂ Me 2-OMe 5-Me 6-225 -CO ₂ Bz Me -Me -CONHMe H 6-226 -CO ₂ Bz Me -Me -CONHBu H 6-227 -CO ₂ Bz Me -Me -CON (Me ) ₂ H 6-228 -CO ₂ Bz Me -Me -CON (Bu) ₂ H 6-229 -CO ₂ Bz Me -Me -CO ₂ HH 6-230 -CO ₂ Bz Me -Me -CO ₂ Me H 6 -231 -CO ₂ Bz H -iPr -CONH ₂ H 6-232 -CO ₂ Bz H -iPr -CONHMe H 6-233 -CO ₂ Bz H -iPr -CON (Me) ₂ H 6-234 -CO ₂ Bz H -iPr -CO ₂ HH 6-235 -CO ₂ Bz H -iPr -CO ₂ Me H 6-236 -CO ₂ Bz H -iPr -CO ₂ Et H 6-237 -CO ₂ Bz H -iBu -CONH ₂ H 6-238 -CO ₂ Bz H -iBu -CONHMe H 6-239 -CO ₂ Bz H -iBu -CON (Me) ₂ H 6-240 -CO ₂ Bz H -iBu -CONHBu H 6-241 -CO ₂ Bz H -iBu -CON (Bu) ₂ H 6-242 -CO ₂ Bz H -iBu -CO-Pyrd (1) H 6-243 -CO ₂ Bz H -iBu -CONH (2-CO ₂ Me-Ph) H 6-244 -CO ₂ Bz H -iBu -CONH (3-CO ₂ Me-Ph) H 6-245 -CO ₂ Bz H -iBu -CONH (4-CO ₂ Me-Ph) H 6-246 -CO ₂ Bz H -iBu -CO ₂ HH 6-247 -CO ₂ Bz H -iBu -CO ₂ Me H 6-248 -CO ₂ Bz H -iBu -CO ₂ Et H 6-249 -CO ₂ Bz H -iBu -CO ₂ Bz H 6-250 -CO ₂ Bz H -iBu -CO ₂ H 2-Me 6-251 -CO ₂ Bz H -iBu -CO ₂ H 2-Me 5-Me 6-252 -CO ₂ Bz H -iBu -CO ₂ H 2-OMe 5-Me 6-253 -CO ₂ Bz H -iBu -CO ₂ Me 2-Me 6-254 -CO ₂ Bz H -iBu -CO ₂ Me 2-Me 5-Me 6-255 -CO ₂ Bz H -iBu -CO ₂ Me 2-OMe 5- Me 6-256 -CO ₂ Bz H -Ph -CONH ₂ H 6-257 -CO ₂ Bz H -Ph -CONHMe H 6-258 -CO ₂ Bz H -Ph -CON (Me) ₂ H 6-259 -CO ₂ Bz H -Ph -CO ₂ HH 6-260 -CO ₂ Bz H -Ph -CO ₂ Me H 6-261 -CO ₂ Bz H -Ph -CO ₂ Et H 6-262 -CO ₂ Bz H -Bz- CONH ₂ H 6-263 -CO ₂ Bz H -Bz -CONHMe H 6-264 -CO ₂ Bz H -Bz -CON (Me) ₂ H 6-265 -CO ₂ Bz H -Bz -CONHBu H 6-266- CO ₂ Bz H -Bz -CON (Bu) ₂ H 6-267 -CO ₂ Bz H -Bz -CO-Pyrd (1) H 6-268 -CO ₂ Bz H -Bz -CONH (2-CO ₂ Me- Ph) H 6-269 -CO ₂ Bz H -Bz -CONH (3-CO ₂ Me-Ph) H 6-270 -CO ₂ Bz H -Bz -CONH (4-CO ₂ Me-Ph) H 6-271 -CO ₂ Bz H -Bz -CO ₂ HH 6-272 -CO ₂ Bz H -Bz -CO ₂ Me H 6- 273 -CO ₂ Bz H -Bz -CO ₂ Et H 6-274 -CO ₂ Bz H -Bz -CO ₂ Bz H 6-275 -CO ₂ Bz H -Bz -CO ₂ H 2-Me 6-276 -CO ₂ Bz H -Bz -CO ₂ H 2-Me 5-Me 6-277 -CO ₂ Bz H -Bz -CO ₂ H 2-OMe 5-Me 6-278 -CO ₂ Bz H -Bz -CO ₂ Me 2 -Me 6-279 -CO ₂ Bz H -Bz -CO ₂ Me 2-Me 5-Me 6-280 -CO ₂ Bz H -Bz -CO ₂ Me 2-OMe 5-Me 6-281 -CO ₂ Bz H -CH ₂ -Ind (3) -CONH ₂ H 6-282 -CO ₂ Bz H -CH ₂ -Ind (3) -CONHMe H 6-283 -CO ₂ Bz H -CH ₂ -Ind (3) -CON ( Me) ₂ H 6-284 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ HH 6-285 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Me H 6-286 -CO ₂ Bz H -CH ₂ -Ind (3) -CO ₂ Et H 6-287 -CO ₂ Bz H -CH ₂ OtBu -CONH ₂ H 6-288 -CO ₂ Bz H -CH ₂ OtBu -CONHMe H 6-289 -CO ₂ Bz H -CH ₂ OtBu -CON (Me) ₂ H 6-290 -CO ₂ Bz H -CH ₂ OtBu -CONHBu H 6-291 -CO ₂ Bz H -CH ₂ OtBu -CON (Bu) ₂ H 6-292 -CO ₂ Bz H -CH ₂ OtBu -CO-Pyrd (1) H 6-293 -CO ₂ Bz H -CH ₂ OtBu -CONH (2-CO ₂ Me-Ph) H 6-294 -CO ₂ Bz H -CH ₂ OtBu -CONH (3-CO ₂ Me-Ph) H 6-295 -CO ₂ Bz H -CH ₂ OtBu -CONH (4-CO ₂ Me-Ph) H 6-296 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ HH 6-297 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me H 6-298 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Et H 6-299 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Bz H 6-300 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-Me 6-301 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-Me 5-Me 6-302 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ H 2-OMe 5-Me 6 -303 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-Me 6-304 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-Me 5-Me 6-305 -CO ₂ Bz H -CH ₂ OtBu -CO ₂ Me 2-OMe 5-Me 6-306 -CO ₂ Bz H -CH (Me) OtBu -CONH ₂ H 6-307 -CO ₂ Bz H -CH (Me) OtBu -CONHMe H 6-308 -CO ₂ Bz H -CH (Me) OtBu -CON (Me) ₂ H 6-309 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ HH 6-310 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Me H 6-311 -CO ₂ Bz H -CH (Me) OtBu -CO ₂ Et H 6-312 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONH ₂ H 6-313 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CONHMe H 6-314 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CON (Me) ₂ H 6-315 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ HH 6-316 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Me H 6-317 -CO ₂ Bz H-(CH ₂ ) ₂ SMe -CO ₂ Et H 6-318 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH ₂ H 6-319 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHMe H 6-320 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Me) ₂ H 6- 321 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONHBu H 6-322 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CON (Bu) ₂ H 6-323 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO-Pyrd (1) H 6 -324 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (2-CO ₂ Me-Ph) H 6-325 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (3-CO ₂ Me-Ph) H 6-326 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CONH (4-CO ₂ Me-Ph) H 6-327 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ HH 6-328 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me H 6-329 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Et H 6-330 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Bz H 6-331 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 6-332 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-Me 5-Me 6-333 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ H 2-OMe 5-Me 6-334 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 6-335 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-Me 5-Me 6-336 -CO ₂ Bz H -CH ₂ CO ₂ tBu -CO ₂ Me 2-OMe 5-Me 6-337 -CO ₂ Bz H-( CH ₂ ) ₂ CO ₂ tBu -CONH ₂ H 6-338 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CONHMe H 6-339 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CON (Me) ₂ H 6-340 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ HH 6-341 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Me H 6- 342 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu -CO ₂ Et H 6-343 -CO ₂ Bz H-(CH ₂ ) ₂ NHCO ₂ Bz -CO ₂ Me H 6-344 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONH ₂ H 6-345 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CONHMe H 6-346 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CON (Me) ₂ H 6-347- CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ HH 6-348 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Me H 6-349 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz -CO ₂ Et H 6-350 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CONH ₂ H 6-351 -CO ₂ Bz H -CH ₂ (4-BzO-Ph ) -CONHMe H 6-352 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CON (Me) ₂ H 6-353 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ HH 6-354 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Me H 6-355 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) -CO ₂ Et H . [Table 7]

[0061]

Embedded image Compd. R ¹ R ² R ^3a R ⁵ 7-1 -HH -HH 7-2 -HH -Me H 7-3 -HH -iPr H 7-4 -HH -iBu H 7-5 -HH -Bz H 7-6 -HH -CH ₂ OtBu H 7 -7 -HH -CH ₂ CO ₂ tBu H 7-8 -Me H -Me H 7-9 -Me H -iBu H 7-10 -Me H -Bz H 7-11 -Me H -CH ₂ OtBu H 7 -12 -Me H -CH ₂ CO ₂ tBu H 7-13 -Ph H -Me H 7-14 -Ph H -iBu H 7-15 -Ph H -Bz H 7-16 -Ph H -CH ₂ OtBu H 7-17 -Ph H -CH ₂ CO ₂ tBu H 7-18 -Ac H -Me H 7-19 -Ac H -iBu H 7-20 -Ac H -Bz H 7-21 -Ac H -CH ₂ OtBu H 7-22 -Ac H -CH ₂ CO ₂ tBu H 7-23 -CO ₂ tBu H -HH 7-24 -CO ₂ tBu H -Me H 7-25 -CO ₂ tBu H -Me 6-Me 7- 26 -CO ₂ tBu H -Me 5-Me 6-Me 7-27 -CO ₂ tBu H -Me 6-OMe 5-Me 7-28 -CO ₂ tBu H -Me 6-Me 7-29 -CO ₂ tBu H -Me 6-Me 5-Me 7-30 -CO ₂ tBu H -Me 6-OMe 5-Me 7-31 -CO ₂ tBu H -Me H 7-32 -CO ₂ tBu H -iPr H 7-33 -CO ₂ tBu H -iBu H 7-34 -CO ₂ tBu H -iBu 6-Me 7-35 -CO ₂ tBu H -iBu 6-Me 5-Me 7-36 -CO ₂ tBu H -iBu 6-OMe 5-Me 7-37 -CO ₂ tBu H -iBu 6-Me 7-38 -CO ₂ tBu H -iBu 6-Me 5-Me 7-39 -CO ₂ tBu H -iBu 6-OMe 5-Me 7- 40 -CO ₂ tBu H -PH H 7-41 -CO ₂ tBu H -Bz H 7-42 -CO ₂ tBu H -Bz 6-Me 7-43 -CO ₂ tBu H -Bz 6-Me 5-Me 7-44 -CO ₂ tBu H -Bz 6-OMe 5-Me 7-45 -CO ₂ tBu H -Bz 6-Me 7-46 -CO ₂ tBu H -Bz 6-Me 5-Me 7- 47 -CO ₂ tBu H -Bz 6-OMe 5-Me 7-48 -CO ₂ tBu H -CH ₂ -Ind (3) H 7-49 -CO ₂ tBu H -CH ₂ OtBu H 7-50 -CO ₂ tBu H -CH ₂ OtBu 6-Me 7-51 -CO ₂ tBu H -CH ₂ OtBu 5-Me 7-52 -CO ₂ tBu H -CH ₂ OtBu 6-OMe 5-Me 7-53 -CO ₂ tBu H -CH ₂ OtBu 6-Me 7-54 -CO ₂ tBu H -CH ₂ OtBu 6-Me 5-Me 7-55 -CO ₂ tBu H -CH ₂ OtBu 6-OMe 5-Me 7-56 -CO ₂ tBu H -CH (Me) OtBu H 7-57 -CO ₂ tBu H-(CH ₂ ) ₂ SMe H 7-58 -CO ₂ tBu H -CH ₂ CO ₂ tBu H 7-59 -CO ₂ tBu H -CH ₂ CO ₂ tBu 6-Me 7-60 -CO ₂ tBu H -CH ₂ CO ₂ tBu 6-Me 5-Me 7-61 -CO ₂ tBu H -CH ₂ CO ₂ tBu 6-OMe 5-Me 7-62- CO ₂ tBu H -CH ₂ CO ₂ tBu 6-Me 7-63 -CO ₂ tBu H -CH ₂ CO ₂ tBu 6-Me 5-Me 7-64 -CO ₂ tBu H -CH ₂ CO ₂ tBu 6-OMe 5-Me 7-65 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu H 7-66 -CO ₂ tBu-(CH ₂ ) ₃ -H 7-67 -CO ₂ Bz H -HH 7-68- CO ₂ Bz H -Me H 7-69 -CO ₂ Bz H -Me 6-Me 7-70 -CO ₂ Bz H -Me 6-Me 5-Me 7-71 -CO ₂ Bz H -Me 6-OMe 5 -Me 7-72 -CO ₂ Bz H -Me 6-Me 7-73 -CO ₂ Bz H -Me 6-Me 5-Me _{7-74 -CO 2 Bz H -Me 6-} OMe 5-Me 7-75 -CO 2 Bz Me -Me H 7-76 -CO 2 Bz H -iPr H 7-77 -CO 2 Bz H -iBu H 7 -78 -CO ₂ Bz H -iBu 6-Me 7-79 -CO ₂ Bz H -iBu 6-Me 5-Me 7-80 -CO ₂ Bz H -iBu 6-OMe 5-Me 7-81 -CO ₂ Bz H -iBu 6-Me 7-82 -CO ₂ Bz H -iBu 6-Me 5-Me 7-83 -CO ₂ Bz H -iBu 6-OMe 5-Me 7-84 -CO ₂ Bz H -PH H 7-85 -CO ₂ Bz H -Bz H 7-86 -CO ₂ Bz H -Bz 6-Me 7-87 -CO ₂ Bz H -Bz 6-Me 5-Me 7-88 -CO ₂ Bz H -Bz 6-OMe 5-Me 7-89 -CO ₂ Bz H -Bz 6-Me 7-90 -CO ₂ Bz H -Bz 6-Me 5-Me 7-91 -CO ₂ Bz H -Bz 6-OMe 5- Me 7-92 -CO ₂ Bz H -CH ₂ -Ind (3) H 7-93 -CO ₂ Bz H -CH ₂ OtBu H 7-94 -CO ₂ Bz H -CH ₂ OtBu 6-Me 7-95- CO ₂ Bz H -CH ₂ OtBu 6-Me 5-Me 7-96 -CO ₂ Bz H -CH ₂ OtBu 6-OMe 5-Me 7-97 -CO ₂ Bz H -CH ₂ OtBu 6-Me 7-98 -CO ₂ Bz H -CH ₂ OtBu 6-Me 5-Me 7-99 -CO ₂ Bz H -CH ₂ OtBu 6-OMe 5-Me 7-100 -CO ₂ Bz H -CH (Me) OtBu H 7- 101 -CO ₂ Bz H-(CH ₂ ) ₂ SMe H 7-102 -CO ₂ Bz H -CH ₂ CO ₂ tBu H 7-103 -CO ₂ Bz H -CH ₂ CO ₂ tBu 6-Me 7-104- CO ₂ Bz H -CH ₂ CO ₂ tBu 6-Me 5-Me 7-105 -CO ₂ Bz H -CH ₂ CO ₂ tBu 6-OMe 5-Me 7-106 -CO ₂ Bz H -CH ₂ CO ₂ tBu 6-Me 7-107 -CO ₂ Bz H -CH ₂ CO ₂ tBu 6-Me 5-Me 7-108 -CO ₂ Bz H -CH ₂ CO ₂ tBu 6-OMe 5 -Me 7-109 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu H 7-110 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz H 7-111 -CO ₂ Bz H -CH ₂ ( 4-BzO-Ph) H 7-112 -CO ₂ Bz-(CH ₂ ) ₃ -H . [Table 8]

[0062]

Embedded image Compd. R ¹ R ² R ^3a Ar ' 8-1 -HH -Me 2-CO ₂ H-Thi (5) 8-2 -HH -Me 2-CO ₂ Me-Thi (5) 8-3 -Me H -Me 2-CO ₂ H-Thi ( 5) 8-4 -Me H -Me 2-CO ₂ Me-Thi (5) 8-5 -Ph H -Me 2-CO ₂ H-Thi (5) 8-6 -Ph H -Me 2-CO ₂ Me-Thi (5) 8-7 -Ac H -Me 2-CO ₂ H-Thi (5) 8-8 -Ac H -Me 2-CO ₂ Me-Thi (5) 8-9 -CO ₂ tBu H -H 2-CO ₂ H-Thi (5) 8-10 -CO ₂ tBu H -H 2-CO ₂ Me-Thi (5) 8-11 -CO ₂ tBu H -Me 2-CONH ₂ -Thi (5 ) 8-12 -CO ₂ tBu H -Me 2-CONHMe-Thi (5) 8-13 -CO ₂ tBu H -Me 2-CON (Me) ₂ -Thi (5) 8-14 -CO ₂ tBu H- Me 2-CONH ₂ -Thi (5) 8-15 -CO ₂ tBu H -Me 2-CON (Bu) ₂ -Thi (5) 8-16 -CO ₂ tBu H -Me 2-CONH (2-CO ₂ Me-Thi (5) -Ph) -Thi (5) 8-17 -CO ₂ tBu H -Me 2-CONH (3-CO ₂ Me-Ph) -Thi (5) 8-18 -CO ₂ tBu H- Me 2-CONH (4-CO ₂ Me-Ph) -Thi (5) 8-19 -CO ₂ tBu H -Me 2-CO ₂ H-Thi (5) 8-20 -CO ₂ tBu H -Me 2- CO ₂ Me-Thi (5) 8-21 -CO ₂ tBu H -Me 2-CO ₂ Et-Thi (5) 8-22 -CO ₂ tBu H -Me 2-CO ₂ Bz-Thi (5) 8- 23 -CO ₂ tBu Me -Me 2-CO ₂ Me-Thi (5) 8-24 -CO ₂ tBu H -iPr 2-CO ₂ H-Thi (5) 8-25 -CO ₂ tBu H -iPr 2- CO ₂ Me-Thi (5) 8-26 -CO ₂ tBu H -iBu 2-CONH ₂ -Thi (5) 8-27 -CO ₂ tBu H -iBu 2-CONHMe-Th i (5) 8-28 -CO ₂ tBu H -iBu 2-CON (Me) ₂ -Thi (5) 8-29 -CO ₂ tBu H -iBu 2-CO ₂ H-Thi (5) 8-30- CO ₂ tBu H -iBu 2-CO ₂ Me-Thi (5) 8-31 -CO ₂ tBu H -iBu 2-CO ₂ Et-Thi (5) 8-32 -CO ₂ tBu H -Ph 2-CO ₂ H-Thi (5) 8-33 -CO ₂ tBu H -Ph 2-CO ₂ Me-Thi (5) 8-34 -CO ₂ tBu H -Bz 2-CONH ₂ -Thi (5) 8-35 -CO ₂ tBu H -Bz 2-CONHMe-Thi (5) 8-36 -CO ₂ tBu H -Bz 2-CON (Me) ₂ -Thi (5) 8-37 -CO ₂ tBu H -Bz 2-CO ₂ H -Thi (5) 8-38 -CO ₂ tBu H -Bz 2-CO ₂ Me-Thi (5) 8-39 -CO ₂ tBu H -Bz 2-CO ₂ Et-Thi (5) 8-40 -CO ₂ tBu H -CH ₂ -Ind (3) 2-CO ₂ H-Thi (5) 8-41 -CO ₂ tBu H -CH ₂ -Ind (3) 2-CO ₂ Me-Thi (5) 8-42 -CO ₂ tBu H -CH ₂ OtBu 2-CONH ₂ -Thi (5) 8-43 -CO ₂ tBu H -CH ₂ OtBu 2-CONHMe-Thi (5) 8-44 -CO ₂ tBu H -CH ₂ OtBu 2-CON (Me) ₂ -Thi (5) 8-45 -CO ₂ tBu H -CH ₂ OtBu 2-CO ₂ H-Thi (5) 8-46 -CO ₂ tBu H -CH ₂ OtBu 2-CO ₂ Me-Thi (5) 8-47 -CO ₂ tBu H -CH ₂ OtBu 2-CO ₂ Et-Thi (5) 8-48 -CO ₂ tBu H -CH (Me) 2OtBu 2-CO ₂ H-Thi ( 5) 8-49 -CO ₂ tBu H -CH (Me) 2OtBu 2-CO ₂ Me-Thi (5) 8-50 -CO ₂ tBu H-(CH ₂ ) ₂ SMe 2-CO ₂ H-Thi (5 ) 8-51 -CO ₂ tBu H-(CH ₂ ) ₂ SMe 2-CO ₂ Me-Thi (5) 8-52 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CONH ₂ -Thi (5) 8-53 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2 -CONHMe-Thi (5) 8-54 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CON (Me) ₂ -Thi (5) 8-55 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CO ₂ H-Thi (5) 8-56 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CO ₂ Me-Thi (5) 8-57 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CO ₂ Et -Thi (5) 8-58 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu 2-CO ₂ H-Thi (5) 8-59 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu 2 -CO ₂ Me-Thi (5) 8-60 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz 2-CO ₂ H-Thi (5) 8-61 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz 2-CO ₂ Me-Thi (5) 8-62 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) 2-CO ₂ H-Thi (5) 8-63 -CO ₂ tBu H- CH ₂ (4-BzO-Ph) 2-CO ₂ Me-Thi (5) 8-64 -CO ₂ Bz H -H 2-CO ₂ H-Thi (5) 8-65 -CO ₂ Bz H -H 2 -CO ₂ Me-Thi (5) 8-66 -CO ₂ Bz H -Me 2-CONH ₂ -Thi (5) 8-67 -CO ₂ Bz H -Me 2-CONHMe-Thi (5) 8-68- CO ₂ Bz H -Me 2-CON (Me) ₂ -Thi (5) 8-69 -CO ₂ Bz H -Me 2-CONHMe-Thi (5) 8-70 -CO ₂ Bz H -Me 2-CON ( Bu) ₂ -Thi (5) 8-71 -CO ₂ Bz H -Me 2-CONH (2-CO ₂ Me-Thi (5) -Ph) -Thi (5) 8-72 -CO ₂ Bz H -Me 2-CONH (3-CO ₂ Me-Ph) -Thi (5) 8- 73 -CO ₂ Bz H -Me 2-CONH (4-CO ₂ Me-Ph) -Thi (5) 8-74 -CO ₂ Bz H -Me 2-CO ₂ H-Thi (5) 8-75 -CO ₂ Bz H -Me 2-CO ₂ Me-Thi (5) 8-76 -CO ₂ Bz H -Me 2-CO ₂ Et-Thi (5) 8-77 -CO ₂ Bz H -Me 2-CO ₂ Bz -Thi (5) 8-78 -CO ₂ Bz Me -Me 2-CO ₂ Me-Thi (5) 8-79 -CO ₂ Bz H -iPr 2-CO ₂ H-Thi (5) 8-80 -CO ₂ Bz H -iPr 2-CO ₂ Me-Thi (5) 8-81 -CO ₂ Bz H -iPr 2-CO ₂ Et-Thi (5) 8-82 -CO ₂ Bz H -iBu 2-CONH _2- Thi (5) 8-83 -CO ₂ Bz H -iBu 2-CONHMe-Thi (5) 8-84 -CO ₂ Bz H -iBu 2-CON (Me) ₂ -Thi (5) 8-85 -CO ₂ Bz H -iBu 2-CO ₂ H-Thi (5) 8-86 -CO ₂ Bz H -iBu 2-CO ₂ Me-Thi (5) 8-87 -CO ₂ Bz H -iBu 2-CO ₂ Et- Thi (5) 8-88 -CO ₂ Bz H -Ph 2-CO ₂ H-Thi (5) 8-89 -CO ₂ Bz H -Ph 2-CO ₂ Me-Thi (5) 8-90 -CO ₂ Bz H -Bz 2-CONH ₂ -Thi (5) 8-91 -CO ₂ Bz H -Bz 2-CONHMe-Thi (5) 8-92 -CO ₂ Bz H -Bz 2-CON (Me) ₂ -Thi (5) 8-93 -CO ₂ Bz H -Bz 2-CO ₂ H-Thi (5) 8-94 -CO ₂ Bz H -Bz 2-CO ₂ Me-Thi (5) 8-95 -CO ₂ Bz H -Bz 2-CO ₂ Et-Thi (5) 8-96 -CO ₂ Bz H -CH ₂ -Ind (3) 2-CO ₂ H-Thi (5) 8-97 -CO ₂ Bz H -CH ₂ -Ind (3) 2-CO ₂ Me-Thi (5) 8-98 -CO ₂ Bz H -CH ₂ OtBu 2-CONH ₂ -T hi (5) 8-99 -CO ₂ Bz H -CH ₂ OtBu 2-CONHMe-Thi (5) 8-100 -CO ₂ Bz H -CH ₂ OtBu 2-CON (Me) ₂ -Thi (5) 8- 101 -CO ₂ Bz H -CH ₂ OtBu 2-CO ₂ H-Thi (5) 8-102 -CO ₂ Bz H -CH ₂ OtBu 2-CO ₂ Me-Thi (5) 8-103 -CO ₂ Bz H -CH ₂ OtBu 2-CO ₂ Et-Thi (5) 8-104 -CO ₂ Bz H -CH (Me) 2OtBu 2-CO ₂ H-Thi (5) 8-105 -CO ₂ Bz H -CH (Me ) 2OtBu 2-CO ₂ Me-Thi (5) 8-106 -CO ₂ Bz H-(CH ₂ ) ₂ SMe 2-CO ₂ H-Thi (5) 8-107 -CO ₂ Bz H-(CH ₂ ) ₂ SMe 2-CO ₂ Me-Thi (5) 8-108 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CONH ₂ -Thi (5) 8-109 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2 -CONHMe-Thi (5) 8-110 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CON (Me) ₂ -Thi (5) 8-111 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CO ₂ H-Thi (5) 8-112 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CO ₂ Me-Thi (5) 8-113 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu 2- CO ₂ H-Thi (5) 8-114 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu 2-CO ₂ Me-Thi (5) 8-115 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz 2-CO ₂ H-Thi (5) 8-116 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz 2-CO ₂ Me-Thi (5) 8-117 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) 2-CO ₂ H-Thi (5) 8-118 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) 2-CO ₂ Me-Thi (5) 8-119 -HH -Me 2- CO ₂ H-Pyr (6) 8-120 -HH -Me 2-CO ₂ Me-Pyr (6) 8-121 -Me H -Me 2-CO ₂ H-Pyr (6) 8-122 -Me H- Me 2-CO ₂ Me-Pyr (6) 8-123 -Ph H -Me 2-CO ₂ H-Pyr (6) 8-124 -Ph H -Me 2-CO ₂ Me-Pyr (6) 8-125 -Ac H -Me 2-CO ₂ H-Pyr (6) 8-126 -Ac H -Me 2-CO ₂ Me-Pyr (6) 8-127 -CO ₂ tBu H -H 2-CO ₂ H-Pyr (6) 8-128 -CO ₂ tBu H -H 2-CO ₂ Me-Pyr (6) 8-129 -CO ₂ tBu H -Me 2-CONH ₂ -Pyr (6) 8-130 -CO ₂ tBu H -Me 2-CONHMe-Pyr (6) 8-131 -CO ₂ tBu H -Me 2-CON (Me) ₂ -Pyr (6) 8-132 -CO ₂ tBu H -Me 2-CONH ₂ -Pyr (6 ) 8-133 -CO ₂ tBu H -Me 2-CON (Bu) ₂ -Pyr (6) 8-134 -CO ₂ tBu H -Me 2-CONH (2-CO ₂ Me-Pyr (6) -Ph) -Pyr (6) 8-135 -CO ₂ tBu H -Me 2-CONH (3-CO ₂ Me-Ph) -Pyr (6) 8-136 -CO ₂ tBu H -Me 2-CONH (4-CO ₂ Me-Ph) -Pyr (6) 8-137 -CO ₂ tBu H -Me 2-CO ₂ H-Pyr (6) 8-138 -CO ₂ tBu H -Me 2-CO ₂ Me-Pyr (6) 8 -139 -CO ₂ tBu H -Me 2-CO ₂ Et-Pyr (6) 8-140 -CO ₂ tBu H -Me 2-CO ₂ Bz-Pyr (6) 8-141 -CO ₂ tBu Me -Me 2 -CO ₂ Me-Pyr (6) 8-142 -CO ₂ tBu H -iPr 2-CO ₂ H-Pyr (6) 8-143 -CO ₂ tBu H -iPr 2-CO ₂ Me-Pyr (6) 8 -144 -CO ₂ tBu H -iBu 2-CONH ₂ -Pyr (6) 8-145 -CO ₂ tB u H -iBu 2-CONHMe-Pyr (6) 8-146 -CO ₂ tBu H -iBu 2-CON (Me) ₂ -Pyr (6) 8-147 -CO ₂ tBu H -iBu 2-CO ₂ H- Pyr (6) 8-148 -CO ₂ tBu H -iBu 2-CO ₂ Me-Pyr (6) 8-149 -CO ₂ tBu H -iBu 2-CO ₂ Et-Pyr (6) 8-150 -CO ₂ tBu H -Ph 2-CO ₂ H-Pyr (6) 8-151 -CO ₂ tBu H -Ph 2-CO ₂ Me-Pyr (6) 8-152 -CO ₂ tBu H -Bz 2-CONH ₂ -Pyr (6) 8-153 -CO ₂ tBu H -Bz 2-CONHMe-Pyr (6) 8-154 -CO ₂ tBu H -Bz 2-CON (Me) ₂ -Pyr (6) 8-155 -CO ₂ tBu H -Bz 2-CO ₂ H-Pyr (6) 8-156 -CO ₂ tBu H -Bz 2-CO ₂ Me-Pyr (6) 8-157 -CO ₂ tBu H -Bz 2-CO ₂ Et-Pyr (6) 8-158 -CO ₂ tBu H -CH ₂ -Ind (3) 2-CO ₂ H-Pyr (6) 8-159 -CO ₂ tBu H -CH ₂ -Ind (3) 2-CO ₂ Me -Pyr (6) 8-160 -CO ₂ tBu H -CH ₂ OtBu 2-CONH ₂ -Pyr (6) 8-161 -CO ₂ tBu H -CH ₂ OtBu 2-CONHMe-Pyr (6) 8-162- CO ₂ tBu H -CH ₂ OtBu 2-CON (Me) ₂ -Pyr (6) 8-163 -CO ₂ tBu H -CH ₂ OtBu 2-CO ₂ H-Pyr (6) 8-164 -CO ₂ tBu H -CH ₂ OtBu 2-CO ₂ Me-Pyr (6) 8-165 -CO ₂ tBu H -CH ₂ OtBu 2-CO ₂ Et-Pyr (6) 8-166 -CO ₂ tBu H -CH (Me) 2OtBu 2-CO ₂ H-Pyr (6) 8-167 -CO ₂ tBu H -CH (Me) 2OtBu 2-CO ₂ Me-Pyr (6) 8-168 -CO ₂ tBu H-(CH ₂ ) ₂ SMe 2-CO ₂ H-Pyr (6) 8-169 -CO ₂ tBu H-(CH ₂ ) ₂ SMe 2-CO ₂ Me-Pyr (6) 8-170 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2 -CONH ₂ -Pyr (6) 8-171 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CONHMe-Pyr (6) 8-172 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CON (Me) ₂ -Pyr (6) 8-173 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CO ₂ H-Pyr (6) 8-174 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CO ₂ Me- Pyr (6) 8-175 -CO ₂ tBu H -CH ₂ CO ₂ tBu 2-CO ₂ Et-Pyr (6) 8-176 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu 2-CO ₂ H -Pyr (6) 8-177 -CO ₂ tBu H-(CH ₂ ) ₂ CO ₂ tBu 2-CO ₂ Me-Pyr (6) 8-178 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz 2 -CO ₂ H-Pyr (6) 8-179 -CO ₂ tBu H-(CH ₂ ) ₄ NHCO ₂ Bz 2-CO ₂ Me-Pyr (6) 8-180 -CO ₂ tBu H -CH ₂ (4- (BzO-Ph) 2-CO ₂ H-Pyr (6) 8-181 -CO ₂ tBu H -CH ₂ (4-BzO-Ph) 2-CO ₂ Me-Pyr (6) 8-182 -CO ₂ Bz H -H 2-CO ₂ H-Pyr (6) 8-183 -CO ₂ Bz H -H 2-CO ₂ Me-Pyr (6) 8-184 -CO ₂ Bz H -Me 2-CONH ₂ -Pyr (6 ) 8-185 -CO ₂ Bz H -Me 2-CONHMe-Pyr (6) 8-186 -CO ₂ Bz H -Me 2-CON (Me) ₂ -Pyr (6) 8-187 -CO ₂ Bz H- Me 2-CONHMe-Pyr (6) 8-188 -CO ₂ Bz H -Me 2-CON (Bu) ₂ -Pyr (6) 8-189 -CO ₂ Bz H -Me 2-CONH (2-CO ₂ Me -Pyr ( 6) -Ph) -Pyr (6) 8-190 -CO ₂ Bz H -Me 2-CONH (3-CO ₂ Me-Ph) -Pyr (6) 8-191 -CO ₂ Bz H -Me 2-CONH (4-CO ₂ Me-Ph) -Pyr (6) 8-192 -CO ₂ Bz H -Me 2-CO ₂ H-Pyr (6) 8-193 -CO ₂ Bz H -Me 2-CO ₂ Me- Pyr (6) 8-194 -CO ₂ Bz H -Me 2-CO ₂ Et-Pyr (6) 8-195 -CO ₂ Bz H -Me 2-CO ₂ Bz-Pyr (6) 8-196 -CO ₂ Bz Me -Me 2-CO ₂ Me-Pyr (6) 8-197 -CO ₂ Bz H -iPr 2-CO ₂ H-Pyr (6) 8-198 -CO ₂ Bz H -iPr 2-CO ₂ Me- Pyr (6) 8-199 -CO ₂ Bz H -iPr 2-CO ₂ Et-Pyr (6) 8-200 -CO ₂ Bz H -iBu 2-CONH ₂ -Pyr (6) 8-201 -CO ₂ Bz H -iBu 2-CONHMe-Pyr (6) 8-202 -CO ₂ Bz H -iBu 2-CON (Me) ₂ -Pyr (6) 8-203 -CO ₂ Bz H -iBu 2-CO ₂ H-Pyr (6) 8-204 -CO ₂ Bz H -iBu 2-CO ₂ Me-Pyr (6) 8-205 -CO ₂ Bz H -iBu 2-CO ₂ Et-Pyr (6) 8-206 -CO ₂ Bz H -Ph 2-CO ₂ H-Pyr (6) 8-207 -CO ₂ Bz H -Ph 2-CO ₂ Me-Pyr (6) 8-208 -CO ₂ Bz H -Bz 2-CONH ₂ -Pyr ( 6) 8-209 -CO ₂ Bz H -Bz 2-CONHMe-Pyr (6) 8-210 -CO ₂ Bz H -Bz 2-CON (Me) ₂ -Pyr (6) 8-211 -CO ₂ Bz H -Bz 2-CO ₂ H-Pyr (6) 8-212 -CO ₂ Bz H -Bz 2-CO ₂ Me-Pyr (6) 8-213 -CO ₂ Bz H -Bz 2-CO ₂ Et-Pyr ( 6) 8-214 -CO ₂ Bz H -CH ₂ -Ind (3) 2-CO ₂ H-Pyr (6) 8-215 -CO ₂ Bz H -CH ₂ -Ind (3) 2-CO ₂ Me-Pyr (6) 8-216 -CO ₂ Bz H -CH ₂ OtBu 2-CONH ₂ -Pyr (6) 8-217 -CO ₂ Bz H -CH ₂ OtBu 2-CONHMe-Pyr (6) 8-218 -CO ₂ Bz H -CH ₂ OtBu 2-CON (Me) ₂ -Pyr (6) 8-219 -CO ₂ Bz H -CH ₂ OtBu 2-CO ₂ H-Pyr (6) 8-220 -CO ₂ Bz H -CH ₂ OtBu 2-CO ₂ Me-Pyr (6) 8-221 -CO ₂ Bz H -CH ₂ OtBu 2-CO ₂ Et-Pyr (6) 8-222 -CO ₂ Bz H -CH (Me) 2OtBu 2-CO ₂ H-Pyr (6) 8-223 -CO ₂ Bz H -CH (Me) 2OtBu 2- CO ₂ Me-Pyr (6) 8-224 -CO ₂ Bz H-(CH ₂ ) ₂ SMe 2-CO ₂ H-Pyr (6) 8-225 -CO ₂ Bz H-(CH ₂ ) ₂ SMe 2- CO ₂ Me-Pyr (6) 8-226 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CONH ₂ -Pyr (6) 8-227 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CONHMe-Pyr (6) 8-228 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CON (Me) ₂ -Pyr (6) 8-229 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CO ₂ H-Pyr (6) 8-230 -CO ₂ Bz H -CH ₂ CO ₂ tBu 2-CO ₂ Me-Pyr (6) 8-231 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu 2-CO ₂ H- Pyr (6) 8-232 -CO ₂ Bz H-(CH ₂ ) ₂ CO ₂ tBu 2-CO ₂ Me-Pyr (6) 8-233 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz 2- CO ₂ H-Pyr (6) 8-234 -CO ₂ Bz H-(CH ₂ ) ₄ NHCO ₂ Bz 2-CO ₂ Me-Pyr (6) 8-235 -CO ₂ Bz H -CH ₂ (4 -BzO-Ph) 2-CO ₂ H-Pyr (6) 8-236 -CO ₂ Bz H -CH ₂ (4-BzO-Ph) 2-CO ₂ Me-Pyr (6) .

[0063]

BEST MODE FOR CARRYING OUT THE INVENTION The compound having the above general formula (II) is produced according to the following synthesis method. In addition, the compound having the general formula (I) of the present invention can be produced by a method similar to the method for producing the compound having the general formula (II).

In the method A, a compound (IIa) in which the broken line is a double bond, R ⁶ is an oxygen atom, and R ⁷ is an ester residue in the compound (II), the broken line is a double bond,
Compound (I) wherein R ⁶ is an oxygen atom and R ⁷ is a hydrogen atom
Ib), and a method for synthesizing a compound (IIc) in which the broken line is a double bond, R ⁶ is an oxygen atom, and R ⁷ is an amine residue.

[0065]

Embedded imageIn the above formula, R¹, R^Two, R^3a, R^Four, R^Five, N and Ar are
Has the same meaning as described above,^1a, R^2a, R^3bAnd R
^5aIs R¹, R^Two, R^3aAnd R^FiveAs a substituent in a group
Amino, hydroxy and / or carboxy groups included
Is an amino, hydroxy and / or
Other R groups¹, R^Two, R^3aAnd R ^FiveDefinition of the group
And the same groups as in^4aIs of the formula -OR^7aTo
Having a group (wherein, R^7aRepresents an ester residue. )
Then R^4bRepresents an amine residue, X represents lithium, mag
Such as nesium, zinc, cadmium, tin, cerium
Represents a metal atom, and Y usually leaves as a nucleophilic residue
There is no particular limitation as long as it is a group, but preferably, chlorine, bromine,
Halogen atom such as iodine; hydroxy group; methanesulfur
Lower alcohols such as honyloxy and ethanesulfonyloxy
Lucanesulfonyloxy group; trifluoromethanesulfo
Nyloxy, pentafluoroethanesulfonyloxy
A halogeno lower alkane sulfonyloxy group such as ben;
Zensulfonyloxy, p-toluenesulfonyloxy
Ali, such as p-nitrobenzenesulfonyloxy
-Sulfonyloxy group, which is most preferable.
Is a halogen atom and trifluoromethanesulfonyl
An oxy group.

In the above, R^1a, R^2a, R^3bAnd R^5a
Of "optionally protected amino group" in the definition of
`` Group '' refers to the protection of amino groups used in the field of synthetic organic chemistry.
The protecting group is not particularly limited as long as it is, for example,
Acetyl, propionyl, butyryl, isobutylyl
, Valeryl, isovaleryl, pivaloyl, hexanoy
Le, acryloyl, methacryloyl, crotonoyl
Lower aliphatic acyl group, chloroacetyl, dichloroa
Cetyl, trichloroacetyl, trifluoroacetyl
Such as a halogeno lower alkylcarbonyl group, methoxyl
Lower alkyl substituted by lower alkoxy such as cetyl
"Aliphatic acyls" such as
With a carbonyl group attached to₇-C₁₁Aromatic acyl group,
Like 2-bromobenzoyl, 4-chlorobenzoyl
Halogeno C₇-C₁₁Aromatic acyl group, 2,4,6-tri
Lower alkyl such as methylbenzoyl and 4-toluoyl
Replaced with₇-C₁₁Aromatic acyl group, 4-aniso
C substituted by lower alkoxy such as yl₇-C₁₁Good
Aromatic acyl group, 4-nitrobenzoyl, 2-nitroben
C substituted with a nitro such as zoyl₇-C₁₁Aromatic
Like a sil group, 2- (methoxycarbonyl) benzoyl
Substituted with a lower alkoxycarbonyl₇-C₁₁Good
An aromatic acyl group, an ant such as 4-phenylbenzoyl;
Replaced with ₇-C₁₁"Aromatic" such as aromatic acyl group
Acyls "; the lower alkoxycarbonyl group, 2,
2,2-trichloroethoxycarbonyl, 2-trimethyl
Halogen or tris such as lucylylethoxycarbonyl
Lower alkoxycarbo substituted by lower alkylsilyl
"Alkoxycarbonyls" such as a nil group; vinyloxy
Alkyl such as carbonyl, allyloxycarbonyl
Nyloxycarbonyls "; benzyloxycarboni
4-methoxybenzyloxycarbonyl, 3,4-
Dimethoxybenzyloxycarbonyl, 2-nitroben
Ziroxycarbonyl, 4-nitrobenzyloxycal
Such as one or two lower alkoxy or
Aralkyl optionally substituted with an aryl ring with toro
Xycarbonyls "; trimethylsilyl, triethylsi
Ryl, isopropyldimethylsilyl, t-butyl dimethyl
Lucyl, methyldiisopropylsilyl, methyldi-t
-Tributylsilyl, triisopropylsilyl
Lower alkylsilyl group, diphenylmethylsilyl, diph
Phenylbutylsilyl, diphenylisopropylsilyl,
Aryls such as phenyldiisopropylsilyl and low
Silyl group substituted by three groups selected from lower alkyl
"Silyls"; benzyl, phenethyl, 3-phenyl
Propyl, α-naphthylmethyl, β-naphthylmethyl
, Diphenylmethyl, triphenylmethyl, α-naph
Like tildiphenylmethyl, 9-anthrylmethyl
A lower alkyl group substituted with one to three aryl groups,
4-methylbenzyl, 2,4,6-trimethylbenzene
3,4,5-trimethylbenzyl, 4-methoxybenzene
Benzyl, 4-methoxyphenyldiphenylmethyl, 2-
Nitrobenzyl, 4-nitrobenzyl, 4-chloroben
Jyl, 4-bromobenzyl, 4-cyanobenzyl, 4-
Cyanobenzyldiphenylmethyl, bis (2-nitroph
Enyl) methyl, lower alkyl such as piperonyl, lower
Aryl ring with higher alkoxy, nitro, halogen, cyano
Is a lower group substituted by 1 to 3 aryl groups
"Aralkyls" such as an alkyl group; or N, N-dimethyl
Luminomethylene, benzylidene, 4-methoxybenzyl
Ridene, 4-nitrobenzylidene, salicylidene, 5-
Chlorosalicylidene, diphenylmethylene, (5-chloro
Like 2- (2-hydroxyphenyl) phenylmethylene
A "substituted methylene group forming a Schiff base";
Yes, preferably a lower aliphatic acyl group, C₇-C₁₁Aroma
An acyl group or an alkoxycarbonyl group, more preferably
Suitably a lower alkoxycarbonyl group, most preferably
Is a t-butoxycarbonyl group.

In the above, R ^1a , R ^2a , R ^3b and R ^5a
The "protecting group" of the "optionally protected hydroxy group" in the definition of is not particularly limited as long as it is a protecting group for a hydroxy group used in the field of organic synthetic chemistry, for example, the lower aliphatic acyl group , Succinoyl, glutaroyl, lower aliphatic acyl groups substituted with carboxy such as adipoyl, chloroacetyl, dichloroacetyl,
Trichloroacetyl, halogeno lower aliphatic acyl group such as trifluoroacetyl, "aliphatic acyl such" such as lower aliphatic acyl group substituted with a lower alkoxy such as methoxy acetyl; the C ₇ -C ₁₁ aromatic acyl Group,
A halogenoarylcarbonyl group such as 2-bromobenzoyl and 4-chlorobenzoyl; a C ₇ -C ₁₁ aromatic acyl group substituted with lower alkyl such as 2,4,6-trimethylbenzoyl and 4-toluoyl; C ₇ -C ₁₁ aromatic acyl group such substituted lower alkoxy as anisoyl, 2-carboxybenzoyl, 3-carboxybenzoyl, 4-carboxyphenyl C ₇ -C ₁₁ aromatic acyl such substituted with carboxy as benzoyl group, 4-nitrobenzoyl, 2-nitrobenzoyl C ₇ -C ₁₁ aromatic acyl group, such substituted with nitro as yl, 2- (methoxycarbonyl) C ₇ -C substituted by lower alkoxycarbonyl, such as benzoyl ₁₁ C ₇ -C substituted with an aromatic acyl group, aryl such as 4-phenylbenzoyl
₁₁ "Aromatic acyls" such as aromatic acyl groups; tetrahydropyran-2-yl, 3-bromotetrahydropyran-
"Tetrahydropyranyl or tetrahydrothiopyranyls" such as 2-yl, 4-methoxytetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, 4-methoxytetrahydrothiopyran-4-yl; tetrahydrofuran-2 -Yl, tetrahydrothiofuran-
"Tetrahydrofuranyl or tetrahydrothiofuranyl" such as 2-yl; trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, t-butyldimethylsilyl, methyldiisopropylsilyl, methyldi-
Three substituted with a group selected from tri-lower alkylsilyl groups such as t-butylsilyl and triisopropylsilyl, aryls such as diphenylmethylsilyl, diphenylbutylsilyl, diphenylisopropylsilyl and phenyldiisopropylsilyl, and lower alkyl. "Silyls" such as silyl group; methoxymethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, t
(Lower alkoxy) methyl groups such as butoxymethyl, (lower alkoxy) methyl groups substituted with lower alkoxy such as 2-methoxyethoxymethyl, 2,2,2
"Alkoxymethyls" such as halogeno (lower alkoxy) methyl such as 2-trichloroethoxymethyl, bis (2-chloroethoxy) methyl; 1-ethoxyethyl;
"Substituted ethyls" such as (lower alkoxy) ethyl group such as 1- (isopropoxy) ethyl, ethyl halide group such as 2,2,2-trichloroethyl; benzyl;
lower alkyl groups substituted with one to three aryl groups such as α-naphthylmethyl, β-naphthylmethyl, diphenylmethyl, triphenylmethyl, α-naphthyldiphenylmethyl, 9-anthrylmethyl; Methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-
Trimethylbenzyl, 4-methoxybenzyl, 4-methoxyphenyldiphenylmethyl, 2-nitrobenzyl,
1 to 3 aryls whose aryl rings are substituted with lower alkyl, lower alkoxy, halogen, cyano such as 4-nitrobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-cyanobenzyl, methyl, piperonyl "Aralkyls" such as a lower alkyl group substituted with a -alkyl group; substituted with a halogen or a tri-lower alkylsilyl group such as the lower alkoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl and 2-trimethylsilylethoxycarbonyl. "Alkoxycarbonyls" such as lower alkoxycarbonyl groups, etc .; "alkenyloxycarbonyls" such as vinyloxycarbonyl and allyloxycarbonyl; benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl 2-nitrobenzyloxycarbonyl, such as 4-nitrobenzyloxycarbonyl, 1
"Aralkyloxycarbonyls" wherein the aryl ring may be substituted with 1 to 2 lower alkoxy or nitro
And is preferably a lower aliphatic acyl group, a C ₇ -C ₁₁ aromatic acyl group, a lower alkoxycarbonyl group or a (lower alkoxy) methyl group, and more preferably a C ₇ -C
_{11 An} aromatic acyl group or a (lower alkoxy) methyl group, most preferably a benzoyl group or a methoxymethyl group.

In the above, R ^1a , R ^2a , R ^3b and R ^5a
"Protecting group of carboxyl group" in the definition of "protecting group" and R ⁵ "Securing which may be a carboxyl group" in the definition of, especially if a protecting group of a carboxy group used in the field of organic synthetic chemistry Without limitation, for example, methyl, ethyl, propyl, isopropyl, butyl, s-
C ₁ -C ₆ alkyl groups such as butyl, t-butyl, benzyl, phenethyl, 3-phenylpropyl, 1-naphthylmethyl, diphenylmethyl, triphenylmethyl,
-C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, nitro, halogen or cyano, such as -methylbenzyl, 4-methoxybenzyl, 4-nitrobenzyl, 4-fluorobenzyl, 4-cyanobenzyl a C ₁ -C ₆ alkyl group substituted with a good one to three C ₆ -C ₁₀ aryl, preferably a C ₁ -C ₆ alkyl group or a benzyl group.

Step A1 is a step of producing a compound having the general formula (IV), which is carried out by Weinreb amidation of a compound having the general formula (III), for example, an azide method and an active esterification method. The reaction is carried out by reacting with N, O-dimethylhydroxylamine or an acid addition salt thereof (for example, a mineral acid salt such as hydrochloride, nitrate or sulfate) by a mixed acid anhydride method or a condensation method.

In the azide method, the compound (III) is reacted with hydrazine in an inert solvent at around room temperature, and then reacted with a nitrite compound to convert the compound into an azide compound.
It is carried out by reacting with dimethylhydroxylamine or an acid addition salt thereof.

Examples of the nitrite used include alkali metal nitrites such as sodium nitrite and alkyl nitrites such as isoamyl nitrite.

Examples of the inert solvent used include, for example,
Examples include amides such as dimethylformamide and dimethylacetamide, sulfoxides such as dimethylsulfoxide, and pyrrolidones such as N-methylpyrrolidone.

The reaction temperature for synthesizing compound (III) into an azide compound varies depending on the starting compound, solvent and the like, but is usually -100 ° C to 50 ° C (preferably -50 ° C).
To 0 ° C.).

The reaction time for synthesizing the compound (III) into an azide compound varies depending on the starting compound, the solvent, the reaction temperature and the like, but is usually from 5 minutes to 24 hours (preferably 1
0 minutes to 10 hours).

Next, the reaction temperature when reacting with N, O-dimethylhydroxylamine or an acid addition salt thereof is usually -50 ° C to 100 ° C (preferably -20 ° C to 5 ° C).
0 ° C).

The reaction time for the reaction with N, O-dimethylhydroxylamine or an acid addition salt thereof is usually 30 minutes to 7 days (preferably 1 hour to 24 hours).

In the active esterification method, the compound (III) is reacted with an active esterifying agent in an inert solvent in the presence or absence (preferably in the presence) of a base to produce an active ester. , O-dimethylhydroxylamine or an acid addition salt thereof.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene , Toluene, xylene; aromatic hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, and carbon tetrachloride; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether Ethers such as formamide, dimethylformamide, dimethylacetamide, amides such as hexamethylphosphoric triamide; preferably halogenated hydrocarbons, ethers or amides, most preferably Dichlorome A down or dimethylformamide.

The active esterifying agent used in the above reaction is, for example, N-hydroxysuccinimide, 1-hydroxybenzotriazole, N-hydroxy-5-norbornene-
N-hydroxy compounds such as 2,3-dicarboximide; diimidazole compounds such as 1,1'-oxalyldiimidazole and N, N'-carbonyldiimidazole; 2,
Disulfide compounds such as 2'-dipyridyl disulfide; succinic compounds such as N, N'-dissuccinimidyl carbonate; N, N'-bis (2-oxo-3-oxazolidinyl) Phosphinic chloride compounds such as phosphinic chloride; N, N'-disuccinimidyl oxalate (DSO), N, N'-diphthalimido oxalate (DPO), N, N'- Bis (norbornenylsuccinimidyl) oxalate (BNO), 1,1'-bis (benzotriazolyl) oxalate (BBTO), 1,1'-bis (6-chlorobenzotriazolyl) Oxalate compounds such as oxalate (BCTO) and 1,1'-bis (6-trifluoromethylbenzotriazolyl) oxalate (BTBO) can be mentioned. Hydroxy compounds or diimidazole compounds, most preferably N-hydroxysac It is a silimide or N, N'-carbonyldiimidazole.

The active esterification reaction is carried out by, for example, di-lower alkyl-triphenylphosphines of azodicarboxylate such as diethyl-triphenylphosphine azodicarboxylate, N-ethyl-5-phenylisoxazolium-3'-sulfonate. N-lower alkyl-5-arylisoxazolium-3'-sulfonates, such as N-, N ', N'-dicycloalkylcarbodiimide, such as N', N'-dicyclohexylcarbodiimide (DCC) , Diheteroaryl diselenides such as di-2-pyridyldiselenide, triarylphosphines such as triphenylphosphine, arylsulfonyltriazolides such as p-nitrobenzenesulfonyltriazolide, 2 2-halo-1-lower alkylpyridinium halides such as -chloro-1-methylpyridinium iodide and diphenylphosphoryl Azide (DPPA)
Diarylphosphoryl azides such as, imidazole derivatives such as N, N'-carbodiimidazole (CDI), 1-
Benzotriazole derivatives such as hydroxybenzotriazole (HOBT), N-hydroxy-5-norbornene-2,3
-Dicarboximide derivatives such as dicarboximide (HONB), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDAPC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDAPC) It is suitably performed in the presence of a condensing agent such as a carbodiimide derivative such as a hydrochloride.

The base used in the above reaction includes, for example, organic lithiums such as n-butyllithium, t-butyllithium and phenyllithium; alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate; Alkali metal bicarbonates such as lithium bicarbonate, sodium bicarbonate and potassium bicarbonate; Alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; lithium hydroxide, sodium hydroxide, hydroxide Alkali metal hydroxides such as potassium; alkali metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide and potassium t-butoxide; triethylamine, tributylamine, diisopropylethylamine, N-methylmorpholine, pyridyl , 4-(N, N-dimethylamino) pyridine, N, N-dimethylaniline, N, N-diethylaniline, 1,5-diazabicyclo [4.3.
0] non-5-ene, 1,4-diazabicyclo [2.
2.2] octane (DABCO), organic amines such as 1,8-diazabicyclo [5.4.0] -7-undecene (DBU); preferably organic amines, most preferably Is triethylamine or diisopropylethylamine.

The reaction temperature varies depending on the starting compound, base, solvent and the like, but is usually -20 ° C to 200 ° C (preferably 0 ° C to 100 ° C).

The reaction time varies depending on the starting compound, base, solvent, reaction temperature and the like, but is usually 5 minutes to 24 hours (preferably 10 minutes to 10 hours).

In the mixed acid anhydride method, the compound (I) is prepared in an inert solvent in the presence or absence (preferably in the presence) of a base.
II) is reacted with a mixed acid anhydride agent to produce mixed acid anhydrides, and then mixed with N, O in an inert solvent.
By reacting dimethylhydroxylamine or an acid addition salt thereof.

The base used in the above reaction includes, for example, the same bases as those used in the active ester method, and is preferably an organic amine, most preferably triethylamine or diisopropylethylamine. It is.

The mixed acid anhydride agent used in the above reaction includes, for example, lower alkyl halides such as ethyl chlorocarbonate and isobutyl chlorocarbonate; lower alkanoyl halides such as pivaloyl chloride; diethyl cyanophosphonate; Di-lower alkyl or diaryl cyanophosphoric acid such as diphenyl phosphonate, preferably di-lower alkyl or diaryl cyanophosphoric acid (most preferably diethyl cyanophosphonate).

The inert solvent used for producing the mixed acid anhydrides is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Aliphatic hydrocarbons such as petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and carbon tetrachloride; diethyl ether Ethers such as, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; ketones such as acetone; amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide; and dimethyl sulfoxide Sulfoxy S; sulfolane; are, preferably, ethers or amides (most preferably tetrahydrofuran or dimethylformamide) is.

The reaction temperature in the reaction for producing the mixed acid anhydrides varies depending on the starting compounds, reagents and the like.
It is 50 ° C to 100 ° C (preferably 0 ° C to 60 ° C).

The reaction time in the reaction for producing the mixed acid anhydrides varies depending on the starting compounds, reagents, reaction temperature and the like, but is usually 30 minutes to 72 hours (preferably 1 hour to 24 hours). is there.

The reaction of the mixed acid anhydrides with N, O-dimethylhydroxylamine or an acid addition salt thereof is carried out in an inert solvent in the presence or absence (preferably in the presence) of a base. The base and the inert solvent used are the same as those used in the reaction for producing the mixed acid anhydrides described above.

The reaction temperature in the reaction of the mixed acid anhydrides with N, O-dimethylhydroxylamine or an acid addition salt thereof varies depending on the starting compounds, reagents and the like, but is usually -3.
It is 0 ° C to 100 ° C (preferably 0 ° C to 80 ° C).

The reaction time in the reaction between the mixed acid anhydrides and N, O-dimethylhydroxylamine or an acid addition salt thereof varies depending on the starting compound, the reagent, the reaction temperature and the like.
Usually, 5 minutes to 24 hours (preferably 30 minutes to 1 hour)
6 hours).

After completion of the reaction, the desired compound (IV)
Is collected from the reaction mixture according to a conventional method. For example,
The reaction mixture is appropriately neutralized, and if insoluble matters are removed by filtration, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. After drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., the solvent is distilled off. If necessary, the obtained target compound can be eluted with a suitable eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds, applying chromatography. Can be separated and purified.

Step A2 is a step of producing a compound having the general formula (VI), and is carried out by the method of Worden et al.
n et al., J. Chem. Soc. (C), 227, 1970). Compound (IV) can be prepared in an inert solvent in the presence or absence of a base (preferably In the presence), and by reacting with a compound having the general formula (V).

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as benzene, toluene, xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether Such ethers; methanol, ethanol
Alcohols such as n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve Ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; water; a mixed solvent of the above solvents; preferably ethers (most preferably tetrahydrofuran).

As the base used in the above reaction, there can be mentioned, for example, the same bases as those used in the above-mentioned active ester method. It is. Further, it can be used by mixing with a potassium salt of t-butyl alcohol.

The reaction temperature varies depending on the starting compound, solvent and the like, but is usually from -120 ° C to 50 ° C (preferably from -10 ° C to -10 ° C).
0 ° C. to 20 ° C.).

The reaction time varies depending on the starting compound, solvent, reaction temperature and the like, but is usually 1 minute to 10 hours (preferably 2 minutes to 5 hours).

After completion of the reaction, the desired compound (VI)
Is collected from the reaction mixture according to a conventional method. For example,
The reaction mixture is appropriately neutralized, and if insoluble matters are removed by filtration, an immiscible organic solvent such as water and ethyl acetate is added, and the organic layer containing the target compound is separated. After drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate, etc., the solvent is distilled off. If necessary, the obtained target compound can be eluted with a suitable eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds, applying chromatography. Can be separated and purified.

In step A3, compound (IIa) is produced.
Process, for example, the method of Sugi et al. (Y. Sugi et a
l., Synlett, 515, 1994).
That is, in an inert solvent, under pressure of carbon monoxide, a transition metal
Compound (VI) having the general formula (VII) in the presence of a catalyst
After reaction with the compound^1a, R^2a, R
^3b, And R^5aAmino, hydroxy and / or mosquito
This is performed by removing the protective group of the ruboxyl group.

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as benzene, toluene, xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide Amides such as
And preferably, aromatic hydrocarbons (most preferably,
Benzene).

Examples of the transition metal catalyst used in the above reaction include copper, palladium, nickel, tetrakistriphenylphosphine palladium, palladium (II) chloride in benzene, and the like. It is a mixture of palladium (II) and bis (diphenylphosphino) propane.

The reaction temperature varies depending on the starting compound, the catalyst, the solvent and the like, but is usually from −0 ° C. to 300 ° C. (preferably −
20 ° C to 200 ° C).

The reaction time varies depending on the starting compound, catalyst, solvent, reaction temperature and the like, but is usually 30 minutes to 7 days (preferably 1 hour to 48 hours).

The removal of protecting groups for the amino, hydroxy and carboxy groups depends on the type, but is generally carried out by methods well known in the art of synthetic organic chemistry, for example, TWGreen,
(Protective Groups in Organic Synthesis), John Wi
ley & Sons: JFWMcOmis, (Protective Groups in Or
ganicChemistry), by the method described in Plenum Press as follows.

When the amino-protecting group is a silyl, a compound which generates a fluorine anion, such as tetrabutylammonium fluoride, hydrofluoric acid, hydrofluoric acid-pyridine and potassium fluoride, is usually used. And removed by treating with.

The solvent used in the above reaction is not particularly limited as long as it does not inhibit the reaction. Examples thereof include ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether. Is preferred.

The reaction temperature and reaction time are not particularly limited, but the reaction is usually carried out at 0 ° C. to 50 ° C. for 10 minutes to 18 hours.

When the protecting group for the amino group is an aliphatic acyl, an aromatic acyl, an alkoxycarbonyl or a substituted methylene group forming a Schiff base, an acid or a base is added in the presence of an aqueous solvent. Can be removed.

The acid used in the above reaction is not particularly limited as long as it is a commonly used acid and does not inhibit the reaction. Examples thereof include hydrobromic acid, hydrochloric acid, sulfuric acid, and the like.
Inorganic acids such as perchloric acid, phosphoric acid and nitric acid, preferably hydrochloric acid.

The base used in the above reaction is not particularly limited as long as it does not affect the other parts of the compound, but is preferably an alkali metal such as lithium carbonate, sodium carbonate or potassium carbonate. Carbonates; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; metal alkoxides such as lithium methoxide, sodium methoxide, sodium ethoxide and potassium-t-butoxide; ammonia water ,
Ammonia, such as concentrated ammonia-methanol.

The solvent used in the above reaction is not particularly limited as long as it is one used in a usual hydrolysis reaction. For example, methanol, ethanol, n-propanol, isopropanol, etc. Alcohols such as toluene, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve;
Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether;
Water; a mixed solvent of water and the above organic solvent; and preferably ethers (most preferably dioxane).

The reaction temperature and the reaction time vary depending on the starting compound, the solvent and the acid or base used, and are not particularly limited. In order to suppress a side reaction, the reaction is usually carried out at 0 ° C. to 150 ° C. for 1 hour. Let react for ~ 10 hours.

When the amino-protecting group is an aralkyl or aralkyloxycarbonyl, it is usually brought into contact with a reducing agent in an inert solvent (preferably by catalytic reduction at room temperature under a catalyst at room temperature). ) A method of removing or using an oxidizing agent is preferred.

The solvent used for the removal by catalytic reduction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; Aromatic hydrocarbons such as toluene, benzene, xylene; methyl acetate,
Esters such as ethyl acetate, propyl acetate, butyl acetate, diethyl carbonate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n- Alcohols such as propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; Water; a mixed solvent of the above solvent and water; preferably alcohols, ethers,
Organic acids or water (most preferably alcohols or organic acids).

The catalyst used for the removal by the catalytic reduction is not particularly limited as long as it is usually used for the catalytic reduction reaction.
Carbon, Raney-nickel, platinum oxide, platinum black, rhodium-
Aluminum oxide, triphenylphosphine-rhodium chloride, palladium-barium sulfate are used.

Although the pressure is not particularly limited, it is usually 1 to 1
It is performed at 0 atm.

The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually from 0 ° C. to 100 ° C.
For 5 minutes to 24 hours.

The solvent used in the removal by oxidation is not particularly limited as long as it does not participate in this reaction, but is preferably a water-containing organic solvent.

Examples of such organic solvents include halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; nitriles such as acetonitrile, diethyl ether, diisopropyl ether, tetrahydrofuran, and the like. Ethers such as dioxane, dimethoxyethane and diethylene glycol dimethyl ether; ketones such as acetone; amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide; and sulfoxides such as dimethylsulfoxide; And preferably halogenated hydrocarbons, ethers or sulfoxides (most preferably halogenated hydrocarbons or sulfoxides).

The oxidizing agent to be used is not particularly limited as long as it is a compound used for oxidation. Preferably, potassium persulfate, sodium persulfate, ammonium cerium nitrate (CAN), 2,3- Dichloro-5,6-
Dicyano-p-benzoquinone (DDQ) is used.

The reaction temperature and the reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually from 0 ° C. to 150 ° C.
For 10 minutes to 24 hours.

When the protecting group for the amino group is an aralkyl, the protecting group can be removed using an acid.

The acid used in the above reaction is not particularly limited as long as it is used as an acid catalyst in a usual reaction. For example, hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid,
Inorganic acids such as phosphoric acid; Bronsted acids such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, and organic acids such as trifluoromethanesulfonic acid; zinc chloride; Tin chloride, boron trichloride, boron trifluoride,
A Lewis acid such as boron tribromide; an acidic ion exchange resin; preferably an inorganic or organic acid (most preferably hydrochloric acid, acetic acid or trifluoroacetic acid).

The inert solvent used in the first-stage reaction is not particularly limited as long as it is inert to the present reaction. Examples thereof include aliphatic hydrocarbons such as hexane, heptane, ligroin, and petroleum ether. Aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane and carbon tetrachloride; methyl acetate, ethyl acetate, propyl acetate, butyl acetate, carbonic acid Esters such as diethyl; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol, isopropanol, and n-butanol. , Isobutanol, t-butanol, Soamiruaruko - le, diethylene glycol, glycerin, octanol, cyclohexanol, alcohol such as methyl cellosolve - Le acids;
Amides such as formamide, dimethylformamide, dimethylacetamide, hexamethylphosphoric triamide; water; or water or a mixed solvent of the above solvents; preferably ethers, alcohols or water (most preferably Is dioxane, tetrahydrofuran, ethanol or water.

The reaction temperature depends on the starting compound, the acid used,
Although it depends on the solvent and the like, it is usually from -20 ° C to the boiling point (preferably 0 ° C to 100 ° C).

The reaction time depends on the starting compound, the acid used,
The time is usually from 15 minutes to 48 hours (preferably from 30 minutes to 20 hours), although it depends on the solvent, the reaction temperature and the like.

When the amino-protecting group is an alkenyloxycarbonyl, the amino-protecting group is usually substituted aliphatic methylene, aromatic acyl, alkoxycarbonyl or a substituted methylene group forming a Schiff base. It is carried out by treating with a base in the same manner as the conditions for the removal reaction in the case of a group.

In the case of an allyloxycarbonyl group,
In particular, the removal method using palladium and triphenylphosphine or nickel tetracarbonyl is simple and can be performed with few side reactions.

When a silyl is used as a protecting group for a hydroxy group, a fluorine anion such as tetrabutylammonium fluoride, hydrofluoric acid, hydrofluoric acid-pyridine, or potassium fluoride is usually formed. Treated with compounds or
Or an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, phosphoric acid or acetic acid, formic acid, oxalic acid, methanesulfonic acid, p
-It can be removed by treatment with an organic acid such as toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid.

When removing with a fluorine anion,
The reaction may be accelerated by adding organic acids such as formic acid, acetic acid, propionic acid.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. Preferably, diethyl ether or diisopropyl ether is used.
Ethers such as ter, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether; nitriles such as acetonitrile and isobutyronitrile; organic acids such as acetic acid; water;

The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually 0 ° C to 100 ° C.
(Preferably 10 ° C. to 50 ° C.) for 1 hour to 24 hours.

When the protecting group for the hydroxy group is an aralkyl or aralkyloxycarbonyl, it is usually contacted with a reducing agent in an inert solvent (preferably by catalytic reduction at room temperature under a catalyst at room temperature). The method of removing or using an oxidizing agent is preferred.

The solvent used for the removal by catalytic reduction is not particularly limited as long as it does not participate in the present reaction. Aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; toluene, benzene , Xylene and the like; aromatic hydrocarbons such as xylene; esters such as ethyl acetate and propyl acetate; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol; Ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol,
Alcohols such as diethylene glycol, glycerin, octanol, cyclohexanol, methyl cellosolve
Amides such as formamide, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone and hexamethylphosphoric triamide; fatty acids such as formic acid and acetic acid; water; a mixed solvent of the above solvents; Preferably they are alcohols (most preferably methanol).

As the catalyst used for the removal by the catalytic reduction, if it is usually used for the catalytic reduction reaction,
Although not particularly limited, for example, palladium-carbon, palladium-black, Raney-nickel, platinum oxide, platinum black, rhodium-aluminum oxide, triphenylphosphine-rhodium chloride, palladium-barium sulfate, and preferably palladium- Carbon.

Although the pressure is not particularly limited, it is usually 1 to 1
It is performed at 0 atm.

The reaction temperature and the reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually from 0 ° C. to 100 ° C.
(Preferably 20 ° C. to 70 ° C.) for 5 minutes to 48 hours (preferably 1 hour to 24 hours).

The solvent used in the removal by oxidation is not particularly limited as long as it does not participate in this reaction, but is preferably a water-containing organic solvent.

As such organic solvents, ketones such as acetone; halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride; nitriles such as acetonitrile; diethyl ether, tetrahydrofuran; Ethers such as dioxane; amides such as dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; and sulfoxides such as dimethylsulfoxide.

The oxidizing agent to be used is not particularly limited as long as it is a compound used for oxidation. Preferably, potassium persulfate, sodium persulfate, ammonium cerium nitrate (CAN), 2,3- Dichloro-5,6-
Dicyano-p-benzoquinone (DDQ) is used.

The reaction temperature and reaction time vary depending on the starting compound, catalyst, solvent and the like, but are usually from 0 ° C. to 150 ° C.
For 10 minutes to 24 hours.

In liquid ammonia or methanol
, Ethanol, n-propanol, isopropanol
, N-butanol, isobutanol, t-butanol
-78 ° C in alcohols such as alcohol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve.
At a temperature of from 0 ° C. to 0 ° C., it can also be removed by the action of alkali metals such as metallic lithium and metallic sodium.

Further, it can be removed by using an alkylsilyl halide such as aluminum chloride-sodium iodide or trimethylsilyl iodide in a solvent.

The solvent to be used is not particularly limited as long as it does not participate in the present reaction, but is preferably a halogenated hydrocarbon such as methylene chloride, chloroform, carbon tetrachloride; or acetonitrile. Nitriles;
A mixed solvent of the above solvents.

The reaction temperature and the reaction time vary depending on the starting compound, the solvent and the like, but are usually carried out at 0 ° C. to 50 ° C. for 5 minutes to 72 hours.

When the reaction substrate has a sulfur atom,
Preferably, aluminum chloride-sodium iodide is used.

When the protecting group for the hydroxy group is an aliphatic acyl, an aromatic acyl or an alkoxycarbonyl group, it is removed by treating with a base in a solvent.

The base used in the above reaction is not particularly limited as long as it does not affect the other parts of the compound. Examples thereof include alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate. Alkali metal bicarbonates such as lithium bicarbonate, sodium bicarbonate and potassium bicarbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; lithium methoxide, sodium methoxide; Metal alkoxides such as sodium ethoxide and potassium t-butoxide; ammonia such as aqueous ammonia and concentrated ammonia-methanol; preferably alkali metal hydroxides, metal alkoxides or ammonia (Most preferably alkali metal hydroxides or metal alkoxides) It is the earth).

The solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction, and examples thereof include diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether. Ethers; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; water; mixed solvents of the above solvents are preferred.

The reaction temperature and reaction time vary depending on the starting compound, base used, solvent and the like, and are not particularly limited.
In order to suppress side reactions, usually -20 ° C to 150 ° C
For 1 to 10 hours.

When the protecting group for the hydroxy group is an alkoxymethyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrofuranyl, tetrahydrothiofuranyl or substituted ethyl, it is usually used in a solvent. , By treatment with an acid.

The acid used is not particularly limited as long as it is usually used as a Bronsted acid or Lewis acid, and is preferably hydrogen chloride; an inorganic acid such as hydrochloric acid, sulfuric acid or nitric acid; or Bronsted acids such as acetic acid, trifluoroacetic acid, methanesulfonic acid, and organic acids such as p-toluenesulfonic acid: Lewis acids such as boron trifluoride, but strongly acidic cations such as Dowex 50W Exchange resins can also be used.

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; aromatic hydrocarbons such as benzene, toluene, xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene,
Halogenated hydrocarbons such as dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate and diethyl carbonate; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl ether Such ethers; methanol, ethanol
Alcohols such as n-propanol, isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve Ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; water; a mixed solvent of the above solvents; preferably ethers (most preferably tetrahydrofuran) or alcohols ( Most preferably, methanol).

The reaction temperature and the reaction time vary depending on the starting compound, the acid used, the solvent and the like, but are usually -10 ° C to 200 ° C (preferably 0 ° C to 150 ° C) for 5 minutes to 48 hours. (Preferably 30 minutes to 10 hours).

When the protecting group for the hydroxy group is an alkenyloxycarbonyl, the conditions for the removal reaction when the protecting group for the hydroxy group is the above-mentioned aliphatic acyl, aromatic acyl or alkoxycarbonyl are usually used. In the same manner as in the above, it is achieved by treating with a base.

In the case of an allyloxycarbonyl group,
In particular, the removal method using palladium and triphenylphosphine, or bis (methyldiphenylphosphine) (1,5-cyclooctadiene) iridium (I) hexafluorophosphate is simple and is carried out with few side reactions. Can be.

When the protecting group for the carboxy group is a lower alkyl group or a lower alkyl group substituted by one to three aryls which may be substituted by lower alkyl, lower alkoxy, nitro, halogen or cyano, This is achieved by treating with a base in the same manner as in the removal reaction when the protecting group for the hydroxy group is an aliphatic acyl, an aromatic acyl or an alkoxycarbonyl.

The removal of the protecting group for the amino, hydroxy and / or carboxy groups can be carried out in any order in the desired order.

After completion of the reaction, the desired compound (II)
a) is collected from the reaction mixture in a conventional manner. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water or the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate or the like, and distilling off the solvent. If necessary, the obtained target compound can be eluted with a suitable eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds, applying chromatography. Can be separated and purified.

Step A4 is a step of producing a compound having the general formula (VIII). This step is performed in the same manner as in the above-mentioned Method A, Step A3.

Step A5 is a step of producing compound (IIb). After reacting compound (VIII) with a base in an inert solvent, if necessary, R ^1a , R ^2a , R ^3b and R ^5a By removing the protecting group of the amino, hydroxy and / or carboxy group in the above.

The base used in the above reaction is not particularly limited as long as it does not affect the other parts of the compound, and examples thereof include alkali metal carbonates such as lithium carbonate, sodium carbonate and potassium carbonate. Alkali metal bicarbonates such as lithium bicarbonate, sodium bicarbonate and potassium bicarbonate; alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; lithium methoxide, sodium methoxide; Metal alkoxides such as sodium ethoxide and potassium tert-butoxide; ammonia such as aqueous ammonia and concentrated ammonia-methanol; preferably alkali metal hydroxides (most preferably hydroxylated Sodium).

The solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction, and examples thereof include diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, and diethylene glycol dimethyl ether. Ethers; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-
Alcohols such as butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; water; mixed solvents of the above solvents, preferably alcohols
(Most preferably methanol).

The reaction temperature and the reaction time vary depending on the starting compound, the base used, the solvent and the like, and are not particularly limited.
In order to suppress side reactions, usually -20 ° C to 150 ° C
(Preferably 0 ° C. to 100 ° C.) for 1 hour to 10 hours.

The method for removing the protecting group of the amino, hydroxy and / or carboxy group in R ^1a , R ^2a , R ^3b and R ^5a , which is carried out as desired, can be carried out by the amino, hydroxy and / or It is carried out in the same manner as the method of removing the protecting group of the carboxy group.

After completion of the reaction, the desired compound (II)
b) is collected from the reaction mixture in a conventional manner. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water or the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate or the like, and distilling off the solvent. If necessary, the obtained target compound can be eluted with a suitable eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds, applying chromatography. Can be separated and purified.

Step A6 is a step of separately producing compound (IIb), which is carried out in an inert solvent under pressure of carbon monoxide.
After reacting the compound (VI) in the presence of a transition metal catalyst and water, if necessary, the protecting group of the amino, hydroxy and / or carboxy group in R ^1a , R ^2a , R ^3b and R ^5a is removed. This step is performed, and the method A
It is performed in the same manner as the three steps.

Step A7 is a step of producing compound (IIc). Compound (VI) is converted to a compound having the general formula (IX) in an inert solvent under carbon monoxide under pressure and in the presence of a transition metal catalyst. After reacting with R ^1a , R ^2a ,
This step is carried out by removing the protecting group for the amino, hydroxy and / or carboxy group in R ^3b and R ^5a , and this step is carried out in the same manner as the above-mentioned Method A, Step A3.

The reaction temperature varies depending on the starting compound, catalyst, solvent and the like, but is usually 0 ° C. to 300 ° C. (preferably 20 ° C.).
° C to 200 ° C).

The reaction time varies depending on the starting compound, catalyst, solvent, reaction temperature and the like, but is usually 30 minutes to 7 days (preferably 1 hour to 48 hours).

In the method B, in the compound (II), the broken line indicates a double bond, R ⁶ is an oxygen atom, and the group having —COR ⁴ forms a hemiacetal structure together with the carbonyl group of the amino acid group. to which compound (IId), and the broken line indicates a double bond, R ⁶ is an oxygen atom, substituted at the ortho position of Ar to a group having a -COR ⁴ amino acid group is substituted, R ⁴ is - ( This is a method for producing a compound (IIe) which is a group having CH ₂ ) ₂ —Y (Y has the same meaning as described above).

[0173]

Embedded image In the above formula, R ¹ , R ^1a , R ² , R ^2a , R ^3a , R ^3b , R ⁵ ,
R ^5a , n, X and Y are as defined above,
Ar ₁ is a compound in which the ortho position of Ar substituted with an amino acid group is a group represented by the formula:
Shows the same groups in the definition of groups of other Ar is Ar substituted with a group having a COR ^4.

Step B1 is a step for producing a compound having the general formula (XI), and in an inert solvent in the presence or absence (preferably in the presence) of a base, compound (IV)
Is reacted with a compound having the general formula (X), and this step is performed in the same manner as in the above-mentioned Method A, Step A2.

Step B2 is a step for producing a compound having the general formula (XII), which is carried out by reacting compound (XI) with a halogeno radical generator and a radical initiator in an inert solvent.

The solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction.
Aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether; benzene, toluene, xylene,
Aromatic hydrocarbons such as carbon tetrachloride; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; diethyl ether, diisopropyl ether;
Tetrahydrofuran, dioxane, dimethoxyethane,
Ethers such as diethylene glycol dimethyl ether; amides such as formamide, dimethylformamide, dimethylacetamide, and hexamethylphosphoric triamide; and preferably aromatic hydrocarbons (most preferably benzene or tetrahydrofuran). Carbon chloride).

The halogeno radical generator used in the above reaction includes, for example, bromine and N-bromosuccinimide.

Examples of the radical initiator used in the above reaction include benzoyl peroxide, azobisisobutyronitrile (AIBN) and the like.

The reaction temperature varies depending on the starting compound, solvent and the like, but is usually from -20 ° C to 200 ° C (preferably from 0 ° C to 150 ° C).

The reaction time varies depending on the starting compound, solvent, reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 12 hours).

After completion of the reaction, the desired compound (XI)
I) is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water or the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate or the like, and distilling off the solvent. If necessary, the obtained target compound can be eluted with a suitable eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds, applying chromatography. Can be separated and purified.

[0182] The B3 step is a step for preparing a compound having the general formula (IId), after the compound (XII) is hydrolyzed, if desired R ^1a, R ^2a, amino in R ^3b and R ^5a, hydroxy And / or by removing the protecting group of the carboxy group.
This is performed in the same manner as in the five steps.

Step B4 is a step of preparing a compound having the general formula (IIe), wherein the amino, hydroxy and / or carboxy groups in R ^1a , R ^2a , R ^3b and R ^5a of compound (XII) are protected. This step is carried out in the same manner as in the method for removing the protecting group for the amino, hydroxy and / or carboxy group in the above-mentioned Method A, Step A3.

In the method C, in the compound (II), the broken line is a single bond, R ⁶ is a hydroxyl group, and R ⁷ is an ester residue (IIf), the broken line is a single bond, and R ⁶ is a single bond. A compound wherein R ⁷ is a hydrogen atom (II)
g), and the broken line is a single bond, R ⁶ is a hydroxyl group,
This is a method for synthesizing a compound (IIh) in which R ⁷ is an amine residue.

[0185]

Embedded image In the above formula, R ¹ , R ^1a , R ² , R ^2a , R ^3a , R ^3b , R ^4a ,
R ^4b , R ⁵ , R ^5a , n, Y and Ar have the same meanings as described above.

Step C1 is a step for producing a compound having the general formula (XIII), and is carried out by the method of Hiyama et al.
iyama et al., J. Am. Chem. Soc., 4629, 1984). That is, the reaction is carried out by reducing the carbonyl group of the amino acid of compound (VI) in an inert solvent.

The inert solvent used in the above reaction is not particularly limited as long as it is inert to the present reaction. For example, aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; benzene , Toluene, xylene; aromatic hydrocarbons such as chloroform, dichloromethane, 1,2-dichloroethane, carbon tetrachloride; acetic acid, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, and carbonic acid Esters such as diethyl; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; methanol, ethanol, n-propanol
, Isopropanol, n-butanol, isobutanol
Alcohols such as toluene, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and methyl cellosolve; amides such as formamide, dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide Water; or water or a mixture of the above solvents; preferably aromatic hydrocarbons, ethers or alcohols (most preferably toluene, ethanol or tetrahydrofuran). .

The reducing agent used in the above reaction is, for example,
Alkali metal borohydrides, such as sodium borohydride, lithium borohydride, sodium cyanoborohydride; aluminum hydride compounds, such as diisobutylaluminum hydride, lithium aluminum hydride, lithium triethoxyaluminum hydride; Yes,
Preferably it is an aluminum hydride compound (most preferably diisobutylaluminum hydride).

The reaction temperature varies depending on the starting compound, the reducing agent used, the type of solvent, and the like, but is usually -150 ° C.
To 250 ° C (preferably -100 ° C to 150 ° C).

The reaction time varies depending on the starting compound, the reducing agent used, the solvent, the reaction temperature and the like, but is usually 15 minutes to 24 hours (preferably 30 minutes to 16 hours).

After completion of the reaction, the desired compound of the present reaction (XII
I) is collected from the reaction mixture according to a conventional method. For example, the reaction mixture is appropriately neutralized, and, if insolubles are present, they are removed by filtration. It is obtained by washing with water or the like, drying with anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrous sodium hydrogen carbonate or the like, and distilling off the solvent. If necessary, the obtained target compound can be eluted with a suitable eluent by applying a conventional method, for example, recrystallization, reprecipitation, etc., by appropriately combining the methods commonly used for separation and purification of organic compounds, applying chromatography. Can be separated and purified.

Step C2 is a step for producing a compound having the general formula (IIf). The step (C2) is carried out in an inert solvent under pressure of carbon monoxide, in the presence of a transition metal catalyst, and in the presence of a transition metal catalyst.
Is reacted with compound (VII), and if desired, R ^1a ,
This step is carried out by removing the protecting group for the amino, hydroxy and / or carboxy group in R ^2a , R ^3b and R ^5a , and this step is carried out in the same manner as the above-mentioned Method A, Step A3.

Step C3 is a step for producing a compound having the general formula (XIV), and the compound (XIII) in an inert solvent under pressure of carbon monoxide and in the presence of a transition metal catalyst.
Is reacted with compound (VII), and this step is performed in the same manner as in the above-mentioned Method A, Step A3.

Step C4 is a step of producing compound (IIg). After reacting compound (XIV) with a base in an inert solvent, if necessary, R ^1a , R ^2a , R ^3b and R ³
This step is carried out by removing the protecting group for the amino, hydroxy and / or carboxy group in ^5a .
This is performed in the same manner as in the method step A5.

Step C5 is a step of separately producing compound (IIg).
After reacting the compound (XIII) in the presence of a transition metal catalyst and water, the amino, hydroxy and / or carboxy group protecting groups in R ^1a , R ^2a , R ^3b and R ^5a are optionally removed. This step is performed in the same manner as the above-mentioned Method A, Step A3.

Step C6 is a step of producing compound (IIh). Compound (XIII) is converted to compound (Ih) in an inert solvent under carbon monoxide under pressure and in the presence of a transition metal catalyst.
X), and optionally by removing the protecting group of the amino, hydroxy and / or carboxy group in R ^1a , R ^2a , R ^3b and R ^5a , this step comprises:
It is performed in the same manner as in the above-mentioned Method A, Step A3.

Starting compounds (III), (V) and (VI)
I), (IX) and (X) are known or are easily prepared according to known methods or methods analogous thereto. [For example, J. Org. Chem., 49, 621 (1984) and the like].

The compound having the above general formula (I) or (II) or a base addition salt or an acid addition salt thereof of the present invention is useful as a peptidomimetic template.

[0199]

The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the scope of the present invention.

The abbreviations in the following formula are as follows. Et: ethyl group Boc: t-butoxycarbonyl group tBu: t-butyl group Cbz: benzyloxycarbonyl group Me: methyl group.

Example 1 3- (Nt-butoxycarbonyl-DL-alanyl)
Methyl benzoate (Exemplary Compound No. 2-93)

[0202]

Embedded image (1a) N ′-(t-butoxycarbonyl) -L-ara
Nin N-methoxy-N-methylamide N- (t-butoxycarbonyl) -L-
To a solution of alanine (22.71 g, 120 mmol) in methylene chloride (400 ml) at room temperature was added triethylamine (41.8 ml, 300 mmol) and N, O-dimethylhydroxylamine hydrochloride (14.05 g, 144 mm).
ol), 1-hydroxybenzotriazole (21.0
8 g, 156 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (29.
96 g, 156 mmol). After completion of the reaction, water (100 ml) was added, and the organic layer was washed with water (100 ml), a saturated aqueous solution of sodium hydrogencarbonate (100 ml) and saturated saline (100 ml), and dried over anhydrous sodium sulfate. The concentrated residue was purified by recrystallization (methylene chloride and hexane) to give the title compound (18.94 g, 68%)
Was obtained as a white solid. NMR spectrum (CDCl ₃ ) δ ppm: 5.25 (1H, brs), 4.69 (1
H, brs), 3.77 (3H, s), 3.21 (3H, s), 1.44 (9H, s), 1.31 (3
H, d, J = 7.3).

(1b) 3- (Nt-butoxycarboni )
Ru-L-alanyl) bromobenzene 1,3-dibromobenzene (4 ml, 3
N-butyl lithium (23.4 ml, 36 mmol) in a solution of 3 mmol) in tetrahydrofuran (100 ml) at -78 ° C.
mmol). Immediately after the dropwise addition, a solution of N '-(t-butoxycarbonyl) -L-alanine N-methoxy-N-methylamide (2.32 g, 10 mmol) in tetrahydrofuran (60 ml) was added, and the mixture was further added at -78 ° C.
Stirred for minutes. After completion of the reaction, saturated aqueous ammonium chloride solution (5
0 ml), diluted with ethyl acetate (100 ml),
The organic layer was separated and dried over anhydrous sodium sulfate. The concentrated residue was purified by silica gel column chromatography (eluent: 5% ethyl acetate / hexane) to give the title compound (3.28 g, 100%) as an oil. Specific rotation: [α] ²³ _D = −7.9 (c = 1.07, CH
Cl ₃ ) High-resolution mass spectrum: actual value [M + H] ⁺ 328.0546 calculated value C ₁₄ H ₁₉ NO ₃ Br 328.0548 IR spectrum (film) ν (cm ⁻¹ ): 3352,1689,1502,14
48,1367,1250,1223,1165,1061 NMR spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, s), 7.89 (1H,
d, J = 7.8), 7.72 (1H, d, J = 6.4), 7.37 (1H, t, J = 7.8), 5.48
(1H, d, J = 7.2), 5.23 (1H, dq, J = 7.2,7.2), 1.46 (9H, s),
1.39 (3H, d, J = 7.0).

(1c) 3- (Nt-butoxycarboni )
Methyl - DL-alanyl) benzoate 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol) in 9% methanol / benzene solution (11 ml) in palladium (II) chloride (9 mg) , 0.05 mmol), 1,3-bis (diphenylphosphino) propane (41 mg, 0.1
mmol) and 1,8-diazabicyclo (5.4.
0) -7-Undecene (75 μl, 0.5 mmol) was added and reacted at 120 ° C. for 7 hours under carbon monoxide pressure (30 atm). After completion of the reaction, the reaction solution is concentrated, and the concentrated residue is subjected to silica gel column chromatography (eluent: 9).
% Ethyl acetate / hexane to 17% ethyl acetate / hexane) to give the title compound (146.6 mg, 95%).
%) As a white solid. Melting point: 89.5-90.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 308.1492 Calculated value C ₁₆ H ₂₂ NO ₅ 308.1498 IR spectrum (KBr) ν (cm ⁻¹ ): 3347, 1722 , 1685,
1515, 1307, 1287, 1253, 1226, 1168, 722 NMR spectrum (CDCl ₃ ) δ ppm: 8.61 (1H, s), 8.27 (1H,
d, J = 7.6), 8.18 (1H, d, J = 7.7), 7.59 (1H, t, J = 7.7), 5.55
(1H, d, J = 7.1), 5.34 (1H, dq, J = 7.2,7.2), 3.96 (3H, s),
1.46 (9H, s), 1.42 (3H, d, J = 7.0).

Example 2 3- (Nt-butoxycarbonyl-DL-alanyl)
Benzoic acid (Exemplary Compound No. 2-92)

[0206]

Embedded image 3- (Nt-butoxycarbonyl-DL-alanyl)
A 1M aqueous solution of sodium hydroxide (1 ml) was added to a solution of methyl benzoate (61 mg, 0.2 mmol) in methanol (1 ml).
ml). After completion of the reaction, 2M hydrochloric acid (1 ml) was added, and the mixture was diluted with ethyl acetate (10 ml). The organic layer was separated and dried over anhydrous sodium sulfate. The concentrated residue was purified by silica gel column chromatography (eluent: 9% methanol / methylene chloride) to give the title compound (37.
(1 mg, 63%) as a white solid. Mp:> 200 ° C. High resolution mass spectrum: Found ^[M-H] - 292.1190 calcd C ₁₅ H ₁₈ NO ₅ 292.1185 IR spectrum ^{(KBr) ν (cm -1)} : 3356, 2980, 1691,
1607, 1520, 1396, 1166 NMR spectrum (CD ₃ CD) δpp
m: 8.63 (1H, s), 8.25 (1H, d, J = 7.7), 8.12 (1H, d, J = 7.8),
7.56 (1H, t, J = 7.8), 5.17 (1H, q, J = 7.1), 1.41 (9H, s),
1.35 (3H, d, J = 7.2).

Example 3 4- (Nt-butoxycarbonyl-DL-alanyl)
Methyl benzoate (Exemplary Compound No. 3-59)

[0208]

Embedded image (3a) 4- (Nt-butoxycarbonyl-L-ara
Nyl ) bromobenzene 1,4-dibromobenzene (1.42 g, 6.0 mmol
1) and N ′-(t-butoxycarbonyl) -L-alanine N-methoxy-N-methylamide (0.47 g,
2.0 mmol) and purified in the same manner as in Example 1b to give the title compound (0.53 g, 81%) as a white solid. Melting point: 91.0-92.0 ° C. Specific rotation: [α] ²³ _D = 3.4 (c = 0.55, CHC
l ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 328.0530 calculated value C ₁₄ H ₁₉ NO ₃ Br 328.0548 IR spectrum (KBr) ν (cm ⁻¹ ): 3356, 1678, 1585,
1520, 1164, 972 NMR spectrum (CDCl ₃ ) δ ppm: 7.84 (2H, d, J = 8.6), 7.
64 (2H, d, J = 8.5), 5.49 (1H, d, J = 7.2), 5.23 (1H, dq, J = 7.
2,7.2), 1.45 (9H, s), 1.39 (3H, d, J = 6.9).

(3b) 4- (Nt-butoxycarboni )
Methyl- (4 -DL-alanyl) benzoate 4- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol)
The reaction was carried out in the same manner as in Example 1c, and purification was performed to obtain the title compound (128.3 mg, 83%) as a white solid. Melting point: 69.0-71.0 ° C High-resolution mass spectrum: Observed value [M + H] ⁺ 308.1510 Calculated value C ₁₆ H ₂₂ NO ₅ 308.1498 IR spectrum (KBr) ν (cm ⁻¹ ): 3340, 1720 , 1686,
1532, 1280, 1176, 1111, 1020, 866, 716 NMR spectrum (CDCl ₃ ) δ ppm: 8.15 (2H, d, J = 8.5), 8.
03 (2H, d, J = 8.4), 5.50 (1H, d, J = 7.3), 5.30 (1H, dq, J = 7.
2,7.2), 3.96 (3H, s), 1.46 (9H, s), 1.40 (3H, d, J = 6.9).

Example 4 3- (Nt-butoxycarbonyl-DL-leucyl)
Methyl benzoate (Exemplary Compound No. 2-158)

[0211]

Embedded image (4a) N ′-(t-butoxycarbonyl) -L-roy
Syn N -methoxy-N-methylamide N- (t-butoxycarbonyl) -L-leucine (1
Using 4.96 g (60 mmol), the reaction was carried out in the same manner as in Example 1a, purified and the title compound (16.46 g, 1 mmol) was obtained.
00%) as an oil. NMR spectrum (CDCl ₃ ) δ ppm: 5.05 (1H, d, J = 8.8), 4.
73 (1H, brs), 3.79 (3H, s), 3.20 (3H, s), 1.74-1.57 (2H,
m), 1.49-1.40 (1H, m), 1.44 (9H, s), 0.97 (3H, d, J = 6.6),
0.93 (3H, d, J = 6.6).

(4b) 3- (Nt-butoxycarboni )
Ru-L-leucyl) bromobenzene 1,3-dibromobenzene (4 ml, 33 mmol) and N '-(t-butoxycarbonyl) -L-leucine
N-methoxy-N-methylamide (2.74 g, 10 m
mol)) and purified in the same manner as in Example 1b, to give the title compound (3.70 g, 100%) as a white solid. Melting point: 63.5-64.0 ° C. Specific rotation: [α] ²³ _D = 15.8 (c = 1.29, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 370.1006 calculated value C ₁₇ H ₂₅ NO ₃ Br 370.1018 IR spectrum (film) ν (cm ⁻¹ ): 3351, 2959, 1689,
1505, 1367, 1234, 1167, 1049, 778, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, s), 7.90 (1H,
d, J = 7.8), 7.71 (1H, d, J = 8.2), 7.37 (1H, t, J = 8.0), 5.36
-5.21 (2H, m), 1.84-1.74 (1H, m), 1.60-1.51 (1H, m), 1.4
4 (9H, s), 1.42-1.27 (1H, m), 1.06 (3H, d, J = 6.5), 0.90 (3
H, d, J = 6.6). (4c) 3- (Nt-butoxycarbonyl-DL-b)
Isyl) methyl benzoate 3- (Nt-butoxycarbonyl-L-leucyl) bromobenzene (185 mg,
0.5 mmol) and purified in the same manner as in Example 1c, followed by purification to give the title compound (126.3 mg, 72%).
Was obtained as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 350.1939 calculated value C ₁₉ H ₂₈ NO ₅ 350.1967 IR spectrum (film) ν (cm ⁻¹ ): 3369, 2958, 1728,
1693, 1511, 1368, 1302, 1166, 766, 715 NMR spectrum (CDCl ₃ ) δ ppm: 8.64 (1H, s), 8.27 (1H,
d, J = 7.9), 8.18 (1H, d, J = 7.8), 7.59 (1H, t, J = 7.8), 5.36
(1H, dt, J = 3.2,9.2), 5.29 (1H, d, J = 8.6), 3.96 (3H, s),
1.85-1.78 (1H, m), 1.61-1.53 (1H, m), 1.49-1.38 (1H, m),
1.45 (9H, s), 1.08 (3H, d, J = 6.5), 0.90 (3H, d, J = 6.7).

Example 5 4- (Nt-butoxycarbonyl-DL-leucyl)
Methyl benzoate (Exemplary Compound No. 3-90)

[0214]

Embedded image (5a) 4- (Nt-butoxycarbonyl-L-roy
Sil) bromobenzene 1,4-dibromobenzene (1.
Using 42 g, 6.0 mmol) and N ′-(t-butoxycarbonyl) -L-leucine N-methoxy-N-methylamide (0.55 g, 2.0 mmol), the reaction was carried out in the same manner as in Example 1b and purified. And the title compound (0.
64 g, 87%) as a white solid. Melting point: 121.0-122.0 ° C. Specific rotation: [α] ²³ _D = 28.4 (c = 0.83, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 370.0996 calculated value C ₁₇ H ₂₅ NO ₃ Br 370.1018 IR spectrum (KBr) ν (cm ⁻¹ ): 3313, 1678, 1588,
1537, 1367, 1284, 1244, 1171 NMR spectrum (CDCl ₃ ) δ ppm: 7.85 (2H, d, J = 8.5), 7.
63 (2H, d, J = 8.6), 5.29-5.22 (2H, m), 1.82-1.75 (1H, m),
1.57-1.37 (2H, m), 1.44 (9H, s), 1.05 (3H, d, J = 6.6), 0.8
9 (3H, d, J = 6.7).

(5b) 4- (Nt-butoxycarboni )
Methyl- ( DL-leucyl) benzoate 4- (Nt-butoxycarbonyl-L-leucyl) bromobenzene (185 mg, 0.5 mmol)
The reaction was conducted in the same manner as in Example 1c, and purification was performed to obtain the title compound (149.9 mg, 86%) as a white solid. Melting point: 76.5-77.5 ° C High-resolution mass spectrum: Observed value [M + H] ⁺ 350.1952 Calculated value C ₁₉ H ₂₈ NO ₅ 350.1968 IR spectrum (KBr) ν (cm ⁻¹ ): 3310, 2960 , 1724,
1680, 1536, 1366, 1286, 1167, 1109, 885, 778, 715 NMR spectrum (CDCl ₃ ) δ ppm: 8.15 (2H, d, J = 8.4), 8.
03 (2H, d, J = 8.4), 5.33 (1H, dt, J = 3.4,9.3), 5.25 (1H, d, J
= 8.7), 3.96 (3H, s), 1.83-1.75 (1H, m), 1.60-1.52 (1H,
m), 1.50-1.39 (1H, m), 1.45 (9H, s), 1.06 (3H, d, J = 6.5),
0.89 (3H, d, J = 6.7).

Example 6 3- (N-benzyloxycarbonyl-DL-valyl)
Methyl benzoate (Exemplary Compound No. 2-142)

[0219]

Embedded image (6a) N ′-(benzyloxycarbonyl) -L-ba
Phosphorus N-methoxy-N-methylamide N- (benzyloxycarbonyl) -L-valine (7.
The reaction was carried out in the same manner as in Example 1a and purified to give the title compound (7.82 g, 89%).
Was obtained as an oil. NMR spectrum (CDCl ₃ ) δ ppm: 7.36 to 7.31 (5H, m), 5.2
0 (1H, d, J = 8.8), 5.13 (1H, d, J = 12.1), 5.06 (1H, d, J = 12.
1), 4.61 (1H, brs), 3.79 (3H, s), 3.22 (3H, s), 2.04-2.0
0 (1H, m), 0.97 (3H, d, J = 7.0), 0.92 (3H, d, J = 6.6).

(6b) 3- (N-benzyloxycarbo )
Nyl- L-valyl) bromobenzene 1,3-dibromobenzene (4 ml, 33 mmol) and N '-(benzyloxycarbonyl) -L-valine
N-methoxy-N-methylamide (2.94 g, 10 m
mol)) and purified in the same manner as in Example 1b, to give the title compound (3.87 g, 99%) as an oil. Specific rotation: [α] ²³ _D = 54.9 (c = 0.97, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 390.0712 calculated value C ₁₉ H ₂₁ NO ₃ Br 390.0705 IR spectrum (film) ν (cm ⁻¹ ): 3348, 2966, 1721,
1686, 1510, 1236, 1096, 1028, 697 NMR spectrum (CDCl ₃ ) δ ppm: 8.09 (1H, s), 7.89 (1H,
d, J = 7.8), 7.73 (1H, d, J = 8.0), 7.42-7.30 (6H, m), 5.63
(1H, d, J = 8.8), 5.23 (1H, dd, J = 4.0,9.0), 5.13 (2H, s),
2.21-2.11 (1H, m), 1.05 (3H, d, J = 6.8), 0.76 (3H, d, J = 6.
8).

(6c) 3- (N-benzyloxycarbo )
Nyl- DL-valyl) methyl benzoate 3- (N-benzyloxycarbonyl-L-valyl) bromobenzene (195 mg, 0.5 mmol) was used.
The reaction was carried out and purified in the same manner as in Example 1c to give the title compound (143.5 mg, 78%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 370.1652 calculated value C ₂₁ H ₂₄ NO ₅ 370.1655 IR spectrum (film) ν (cm ⁻¹ ): 3366, 2965, 1726,
1689, 1510, 1301, 1213, 1097, 757, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.28 (1H, s), 8.28 (1H,
d, J = 7.8), 8.16 (1H, d, J = 7.7), 7.59 (1H, t, J = 7.8), 7.38
-7.31 (5H, m), 5.69 (1H, d, J = 8.8), 5.34 (1H, dd, J = 4.1,8.
8), 5.13 (2H, s), 3.97 (3H, s), 2.19-2.13 (1H, m), 1.07
(3H, d, J = 6.9), 0.76 (3H, d, J = 6.9).

Example 7 4- (N-benzyloxycarbonyl-DL-valyl)
Methyl benzoate (Exemplary Compound No. 3-235)

[0221]

Embedded image (7a) 4- (N-benzyloxycarbonyl-L-ba
(Ryl ) bromobenzene 1,4-dibromobenzene (1.42 g, 6.0 mmol
1) and N ′-(t-butoxycarbonyl) -L-valine N-methoxy-N-methylamide (0.59 g,
2.0 mmol), and purified in the same manner as in Example 1b to give the title compound (0.78 g, 100%) as a white solid. Melting point: 79.0-80.0 ° C. Specific rotation: [α] ²³ _D = 82.8 (c = 0.43, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 390.0699 calculated value C ₁₉ H ₂₁ NO ₃ Br 390.0705 IR spectrum (KBr) ν (cm ⁻¹ ): 3307, 1677, 1586,
1537, 1254, 1217 NMR spectrum (CDCl ₃ ) δ ppm: 7.84 (2H, d, J = 8.6), 7.
64 (2H, d, J = 8.5), 7.37-7.32 (5H, m), 5.64 (1H, d, J = 8.9),
5.22 (1H, dd, J = 4.2,8.9), 5.12 (2H, s), 2.18-2.10 (1H,
m), 1.04 (3H, d, J = 6.7), 0.76 (3H, d, J = 6.8) (7b) 4- (N-benzyloxycarbonyl-DL-
Methyl (valyl ) benzoate 3- (N-benzyloxycarbonyl-L-valyl) bromobenzene (195 mg, 0.5 mmol)
The reaction was conducted in the same manner as in Example 1c, and purification was performed to obtain the title compound (131.3 mg, 71%) as a white solid. Melting point: 86.0-87.0 ° C. High-resolution mass spectrum: observed value [M + H] ⁺ 370.1643 calculated value C ₂₁ H ₂₄ NO ₅ 370.1654 IR spectrum (KBr) ν (cm ⁻¹ ): 3331, 2964 , 1723,
1677, 1530, 1283, 1252, 1215, 1109 NMR spectrum (CDCl ₃ ) δ ppm: 8.15 (2H, d, J = 8.3), 8.
02 (2H, d, J = 8.4), 7.37-7.31 (5H, m), 5.65 (1H, d, J = 8.8),
5.30 (1H, dd, J = 4.2,8.9), 5.13 (2H, s), 3.96 (3H, s), 2.
18-2.04 (1H, m), 1.05 (3H, d, J = 6.7), 0.76 (3H, d, J = 6.
8).

Example 8 3- (N-benzyloxycarbonyl-DL-phenyl)
Methyl alanyl) benzoate (Exemplary Compound No. 2-46)
7)

[0223]

Embedded image (8a) N ′-(benzyloxycarbonyl) -L-F
Example 1 using enylalanine N -methoxy-N-methylamide N- (benzyloxycarbonyl) -L-phenylalanine (29.9 g, 100 mmol).
The reaction was carried out in the same manner as in Example 1a, purified and the title compound (33.9)
(8 g, 99%) as an oil. NMR spectrum (CDCl ₃ ) δ ppm: 7.36-7.14 (10H, m), 5.
42 (1H, d, J = 8.8), 5.09 (1H, d, J = 12.5), 5.03 (1H, d, J = 12.
5), 4.98 (1H, brs), 3.68 (3H, s), 3.18 (3H, s), 3.08 (1H,
dd, J = 5.9, 13.5), 2.91 (1H, dd, J = 7.0, 13.5) (8b) 3- (N-benzyloxycarbonyl-L-f
Enylalanyl) bromobenzene 1,3-dibromobenzene (4 ml, 33 mmol) and N '-(benzyloxycarbonyl) -L-phenylalanine N-methoxy-N-methylamide (3.42
g, 10 mmol) and purified in the same manner as in Example 1b, followed by purification to give the title compound (4.38 g, 100%).
Was obtained as an oil. Specific rotation: [α] ²³ _D = 45.0 (c = 1.29, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 438.0722 calculated value C ₂₃ H ₂₁ NO ₃ Br 438.0705 IR spectrum (film) ν (cm ⁻¹ ): 3329, 3064, 3031,
1689, 1498, 1253, 1220, 1059, 749, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.03 (1H, s), 7.84 (1H,
d, J = 7.9), 7.71 (1H, d, J = 8.3), 7.38-7.18 (9H, m), 7.10-
6.96 (2H, m), 5.62 (1H, d, J = 7.7), 5.60-5.50 (1H, m), 5.1
3 (1H, d, J = 12.2), 5.09 (1H, d, J = 12.2), 3.21 (1H, dd, J = 6.
3,14.0), 3.01 (1H, dd, J = 5.7,14.0).

(8c) 3- (N-benzyloxycarbo )
Nyl-DL-phenylalanyl) benzoic acid methyl 3- (N-benzyloxycarbonyl-L-phenylalanyl) bromobenzene (219 mg, 0.5 mmol)
Using l), the reaction was carried out in the same manner as in Example 1c, purified, and
The title compound (162.6 mg, 78%) was obtained as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 418.1656 calculated value C ₂₅ H ₂₄ NO ₅ 418.1654 IR spectrum (film) ν (cm ⁻¹ ): 3351, 3031, 2952,
1726, 1691, 1499, 1303, 1216, 749, 699 NMR spectrum (CDCl ₃ ) δ ppm: 8.56 (1H, s), 8.26 (1H,
d, J = 7.6), 8.10 (1H, d, J = 7.7), 7.56 (1H, t, J = 7.8), 7.38
-7.31 (5H, m), 7.21-7.17 (3H, m), 6.97-6.95 (2H, m), 5.6
8 (1H, d, J = 7.9), 5.65-5.60 (1H, m), 5.14 (1H, d, J = 12.3),
5.10 (1H, d, J = 12.3), 3.97 (3H, s), 3.24 (1H, dd, J = 6.1,1
4.0), 3.04 (1H, dd, J = 5.4,14.0).

Example 9 4- (N-benzyloxycarbonyl-DL-phenyl)
Methyl alanyl) benzoate (Exemplary Compound No. 3-27)
2)

[0226]

Embedded image (9a) 4- (N-benzyloxycarbonyl-L-F
Enylalanyl) bromobenzene 1,4-dibromobenzene (1.42 g, 6.0 mmol)
l) and N ′-(benzyloxycarbonyl) -L-phenylalanine N-methoxy-N-methylamide (0.68 g, 2.0 mmol), the reaction was carried out in the same manner as in Example 1b, and the title compound was purified. (0.88
g, 100%) as a white solid. Melting point: 103.0-104.0 ° C. Specific rotation: [α] ²³ _D = 38.8 (c = 0.89, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + Na] ⁺ 460.0495 calculated value C ₂₃ H ₂₀ NO ₃ BrNa 460.0524 IR spectrum (KBr) ν (cm ⁻¹ ): 3316, 1684, 1585,
1536, 1264, 749, 697 NMR spectrum (CDCl ₃ ) δ ppm: 7.78 (2H, d, J = 8.5), 7.
61 (2H, d, J = 8.6), 7.38-7.32 (5H, m), 7.20-7.18 (3H, m),
6.98-6.95 (2H, m), 5.63 (1H, d, J = 8.0), 5.55-5.50 (1H,
m), 5.13 (1H, d, J = 12.2), 5.08 (1H, d, J = 12.2), 3.22 (1H,
dd, J = 6.1, 13.9), 3.00 (1H, dd, J = 5.6, 13.9).

(9b) 4- (N-benzyloxycarbo )
Nyl-DL-phenylalanyl) benzoic acid methyl 4- (N-benzyloxycarbonyl-L-phenylalanyl) bromobenzene (219 mg, 0.5 mmol)
Using l), the reaction was carried out in the same manner as in Example 1c, purified, and
The title compound (183.4 mg, 88%) was obtained as a white solid. Melting point: 85.5-87.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 418.1655 Calculated value C ₂₅ H ₂₄ NO ₅ 418.1654 IR spectrum (KBr) ν (cm ⁻¹ ): 3338, 1718 , 1685,
1531, 1285, 1110, 697 NMR spectrum (CDCl ₃ ) δ ppm: 8.12 (2H, d, J = 8.4), 7.
97 (2H, d, J = 8.3), 7.38-7.31 (5H, m), 7.19-7.18 (3H, m),
6.97-6.95 (2H, m), 5.66-5.57 (2H, m), 5.14 (1H, d, J = 12.
3), 5.09 (1H, d, J = 12.2), 3.96 (3H, s), 3.24 (1H, dd, J = 6.
0,14.0), 3.02 (1H, dd, J = 5.6,14.0) Example 10 3- (Nt-butoxycarbonylglycyl) benzoic acid
Methyl (Exemplified Compound No. 2-70)

[0228]

Embedded image (10a) N ′-(t-butoxycarbonyl) glycine
N-methoxy-N-methylamide N- (t-butoxycarbonyl) glycine (10.51
g, 60 mmol) and purified in the same manner as in Example 1a to give the title compound (10.91 g, 83%) as a white solid. NMR spectrum (CDCl ₃ ) δ ppm: 5.27 (1H, brs), 4.08 (2
H, brs), 3.72 (3H, s), 3.21 (3H, s), 1.46 (9H, s).

(10b) 3- (Nt-butoxycarbo )
Nylglycyl) bromobenzene 1,3-dibromobenzene (4 ml, 33 mmol) and N ′-(t-butoxycarbonyl) glycine N-methoxy-N-methylamide (2.18 g, 10 mmol)
Using l), the reaction was carried out in the same manner as in Example 1b, followed by purification to obtain the title compound (2.65 g, 84%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 316.0342 calculated value C ₁₃ H ₁₇ NO ₃ Br 316.0371 IR spectrum (film) ν (cm ⁻¹ ): 3428, 2978, 1694,
1504, 1367, 1218, 1168, 782, 681 NMR spectrum (CDCl ₃ ) δ ppm: 8.10 (1H, s), 7.87 (1H,
d, J = 7.9), 7.74 (1H, d, J = 8.3), 7.38 (1H, t, J = 7.9), 5.48
(1H, brs), 4.63 (2H, d, J = 4.5), 1.48 (9H, s).

(10c) 3- (Nt-butoxycarbo )
Using methyl 3- (Nt-butoxycarbonylglycyl) bromobenzene (157 mg, 0.5 mmol), the reaction was carried out in the same manner as in Example 1c, purification was carried out, and the title compound (10
(3.2 mg, 70%) as an oil. High-resolution mass spectrum: measured value [M + Na] ⁺ 316.1152 calculated value C ₁₅ H ₁₉ NO ₅ Na 316.1161 IR spectrum (film) ν (cm ⁻¹ ): 3389, 2979, 1726,
1507, 1367, 1289, 1214, 1167, 754 NMR spectrum (CDCl ₃ ) δ ppm: 8.60 (1H, s), 8.28 (1H,
d, J = 7.3), 8.16 (1H, d, J = 8.1), 7.60 (1H, t, J = 8.1), 5.55
(1H, brs), 4.71 (2H, d, J = 3.7), 3.97 (3H, s), 1.49 (9H, s)
Example 11 4- (Nt-butoxycarbonylglycyl) benzoic acid
Methyl (Exemplified Compound No. 3-45)

[0231]

Embedded image (11a) 4- (Nt-butoxycarbonylglyci )
B) bromobenzene 1,4-dibromobenzene (1.42 g, 6.0 mmol
l) and N '-(t-butoxycarbonyl) glycine
N-methoxy-N-methylamide (0.44 g, 2.0
The reaction was carried out in the same manner as in Example 1b and purified to give the title compound (0.42 g, 67%) as a white solid. Melting point: 84.5-85.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 316.0351 Calculated value C ₁₃ H ₁₇ NO ₃ Br 316.0371 IR spectrum (KBr) ν (cm ⁻¹ ): 3356, 1675, 1586,
1530, 1368, 1298, 1230, 1167 NMR spectrum (CDCl ₃ ) δ ppm: 7.82 (2H, d, J = 8.4), 7.
64 (2H, d, J = 8.4), 5.51 (1H, brs), 4.62 (2H, d, J = 4.5), 1.
48 (9H, s).

(11b) 4- (Nt-butoxycarbo )
Methyl ( nylglycyl) benzoate 4- (Nt-butoxycarbonylglycyl) bromobenzene (157 mg, 0.5 mmol) was reacted in the same manner as in Example 1c, purified, and purified to obtain the title compound (11).
(4.3 mg, 78%) as a white solid. Melting point: 72.0-74.0 ° C High-resolution mass spectrum: Observed value [M + H] ⁺ 294.1339 Calculated value C ₁₅ H ₂₀ NO ₅ 294.1341 IR spectrum (KBr) ν (cm ⁻¹ ): 3391, 2985 , 1725,
1710, 1685, 1497, 1360, 1282, 1222, 1175, 1109, 767 NMR spectrum (CDCl
₃ ) δppm: 8.15 (2H, d, J = 8.3), 8.01 (2H, d, J = 8.5), 5.52
(1H, brs), 4.69 (2H, d, J = 4.6), 3.96 (3H, s), 1.48 (9H,
s).

Example 12 3- (Nt-butoxycarbonyl-DL-methioni
B) Methyl benzoate (Exemplary Compound No. 2-268)

[0234]

Embedded image (12a) N ′-(t-butoxycarbonyl) -L-me
The reaction was carried out in the same manner as in Example 1a using thionine N -methoxy-N-methylamide N- (t-butoxycarbonyl) -L-methionine (7.48 g, 30 mmol), and the title compound (6.87 g, 7
8%) as an oil. NMR spectrum (CDCl ₃ ) δ ppm: 5.23 (1H, d, J = 8.8), 4.
80 (1H, brs), 3.79 (3H, s), 3.22 (3H, s), 2.58-2.50 (2H,
m), 2.10 (3H, s), 1.82-1.77 (1H, m), 1.61-1.58 (1H, m),
1.44 (9H, s).

(12b) 3- (Nt-butoxycarbo )
N-L-methionyl) bromobenzene 1,3-dibromobenzene (0.73 ml, 6.0 mm
ol) and N '-(t-butoxycarbonyl) -L-methionine N-methoxy-N-methylamide (0.59
g, 2.0 mmol) and purified in the same manner as in Example 1b, followed by purification to give the title compound (0.69 g, 89%).
Was obtained as an oil. Specific rotation: [α] ²³ _D = 7.3 (c = 0.89, CHC
l ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 388.0565 calculated value C ₁₆ H ₂₃ NO ₃ BrS 388.0592 IR spectrum (film) ν (cm ⁻¹ ): 3350, 2977, 2919,
2688, 1503, 1367, 1251, 1230, 1167 NMR spectrum (CDCl ₃ ) δ ppm: 8.16 (1H, s), 7.95 (1H,
d, J = 7.9), 7.73 (1H, d, J = 8.3), 7.38 (1H, t, J = 8.0), 5.50
-5.39 (2H, m), 2.61-2.50 (2H, m), 2.17-2.11 (1H, m), 2.0
7 (3H, s), 1.81-1.73 (1H, m), 1.45 (9H, s).

(12c) 3- (Nt-butoxycarbo )
Nyl-DL-methionyl) methyl benzoate 3- (Nt-butoxycarbonyl-L-methionyl)
The reaction was carried out in the same manner as in Example 1c using bromobenzene (194 mg, 0.5 mmol) and purification was performed to obtain the title compound (120.5 mg, 65%) as an oil. High-resolution mass spectrum: measured value [M + Na] ⁺ 390.1349 calculated value C ₁₈ H ₂₅ NO ₅ SNa 390.1351 IR spectrum (film) ν (cm ⁻¹ ): 3367, 2977, 1726,
1691, 1509, 1437, 1367, 1303, 1226, 1167, 759, 71
8 NMR spectrum (CDCl ₃ ) δ ppm: 8.66 (1H, s), 8.28 (1H,
d, J = 7.2), 8.21 (1H, d, J = 7.9), 7.60 (1H, t, J = 7.9), 5.50
(2H, brs), 3.96 (3H, s), 2.66-2.59 (1H, m), 2.57-2.49 (1
H, m), 2.20-2.10 (1H, m), 2.05 (3H, s), 1.85-1.76 (1H,
m), 1.46 (9H, s).

Example 13 4- (Nt-butoxycarbonyl-DL-methioni
B) Methyl benzoate (Exemplary Compound No. 3-159)

[0238]

Embedded image (13a) 4- (Nt-butoxycarbonyl-L-me
Thionyl) bromobenzene 1,4-dibromobenzene (1.42 g, 6.0 mmol)
1) and N ′-(t-butoxycarbonyl) -L-methionine N-methoxy-N-methylamide (0.59
g, 2.0 mmol) and purified in the same manner as in Example 1b, followed by purification to give the title compound (0.74 g, 95%).
Was obtained as a white solid. Melting point: 68.0-69.0 ° C. Specific rotation: [α] ²³ _D = 16.1 (c = 0.75, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + Na] ⁺ 410.0394 calculated value C ₁₆ H ₂₂ NO ₃ BrSNa 410.0402 IR spectrum (KBr) ν (cm ⁻¹ ): 3359, 1678, 1586,
1523, 1167, 1070 NMR spectrum (CDCl ₃ ) δ ppm: 7.89 (2H, d, J = 8.7), 7.
64 (2H, d, J = 8.4), 5.45-5.38 (2H, m), 2.64-2.48 (2H, m),
2.16-2.07 (2H, m), 2.06 (3H, s), 1.84-1.74 (1H, m), 1.45
(9H, s).

(13b) 4- (Nt-butoxycarbo )
Nyl-DL-methionyl) methyl benzoate 4- (Nt-butoxycarbonyl-L-methionyl)
The reaction was carried out in the same manner as in Example 1c using bromobenzene (194 mg, 0.5 mmol), and purification was performed to obtain the title compound (162.8 mg, 88%) as a white solid. Melting point: 60.0-61.0 ° C High-resolution mass spectrum: Observed value [M + H] ⁺ 368.1529 Calculated value C ₁₈ H ₂₆ NO ₅ S 368.1522 IR spectrum (KBr) ν (cm ⁻¹ ): 3372, 2979, 1726,
1684, 1518, 1284, 1165, 1111, 714 NMR spectrum (CDCl ₃ ) δ ppm: 8.16 (2H, d, J = 8.3), 8.
08 (2H, d, J = 8.4), 5.46 (2H, brs), 3.96 (3H, s), 2.65-2.5
0 (2H, m), 2.18-2.09 (1H, m), 2.05 (3H, s), 1.84-1.75 (1
H, m), 1.45 (9H, s).

Example 14 3- (Nt-butoxycarbonyl-DL-prolyl)
Methyl benzoate (Exemplary Compound No. 2-619)

[0241]

Embedded image (14a) N ′-(t-butoxycarbonyl) -L-p
Loline N-methoxy-N-methylamide N- (t-butoxycarbonyl) -L-proline (1
Using 2.92 g (60 mmol), the reaction was carried out in the same manner as in Example 1a, purified, and the title compound (10.44 g, 6 mmol) was obtained.
7%) as an oil.

(14b) 3- (Nt-butoxycarbo )
Nyl-L-prolyl) bromobenzene Under a nitrogen atmosphere, 1,3-dibromobenzene (0.48 m
1,4.0 mmol) in tetrahydrofuran (20 m
l) Add n-butyllithium (3.1 m
1,4.8 mmol) was added. Immediately after dropping, N'-
(T-butoxycarbonyl) -L-proline N-methoxy-N-methylamide (0.524 g, 2 mmol)
Of tetrahydrofuran (10 ml) was added, and the mixture was further stirred at -78 ° C for 5 minutes. After completion of the reaction, saturated aqueous ammonium chloride (10 ml) was added to terminate the reaction. After dilution with ethyl acetate (20 ml), the organic layer was separated and dried over anhydrous sodium sulfate. The concentrated residue is subjected to silica gel column chromatography (elution solvent: 9% ethyl acetate /
Hexane to 17% ethyl acetate / hexane)
The title compound (0.32 g, 45%) was obtained as white crystals. Melting point: 62.0-65.0 ° C. Specific rotation: [α] ²³ _D = -21.2 (c = 0.45, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + Na] ⁺ 376.0516 calculated value C ₁₆ H ₂₀ NO ₃ BrNa 376.0524 IR spectrum (KBr) ν (cm ⁻¹ ): 2972, 2873, 1709,
1393, 1220, 1161, 1126, 775, 582.

(14c) 3- (Nt-butoxycarbo )
Using methyl 3- (Nt-butoxycarbonyl-L-prolyl) bromobenzene (177 mg, 0.5 mmol),
The reaction was performed and purified in the same manner as in Example 1c to give the title compound (104.6 mg, 63%) as an oil. High-resolution mass spectrum: measured value [M + Na] ⁺ 356.1471 calculated value C ₁₈ H ₂₃ NO ₅ Na 356.1474 IR spectrum (film) ν (cm ⁻¹ ): 3493, 2976, 1727,
1400, 1302, 1209, 1165, 769, 719.

Example 15 4- (Nt-butoxycarbonyl-DL-prolyl)
Methyl benzoate (Exemplary Compound No. 3-360)

[0245]

Embedded image (15a) 4- (Nt-butoxycarbonyl-L-p
(Loryl) bromobenzene 1,4-dibromobenzene (0.94 g, 4.0 mmol
1) and N ′-(t-butoxycarbonyl) -L-proline N-methoxy-N-methylamide (0.52 g,
Using 2.0 mmol), the reaction was carried out in the same manner as in Example 14b, followed by purification to obtain the title compound (0.37 g, 53%) as a white solid. Melting point: 113.0-115.0 ° C. Specific rotation: [α] ²³ _D = 18.9 (c = 1.13, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + Na] ⁺ 376.0500 calculated value C ₁₆ H ₂₀ NO ₃ BrNa 376.0524 IR spectrum (KBr) ν (cm ⁻¹ ): 1592, 1585, 1407,
1224, 1159.

(15b) 4- (Nt-butoxycarbo )
Using methyl 4- (Nt-butoxycarbonyl-L-prolyl) bromobenzene (177 mg, 0.5 mmol),
The reaction was conducted in the same manner as in Example 1c, and purification was performed to obtain the title compound (122.9 mg, 74%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 334.1651 calculated value C ₁₈ H ₂₄ NO ₅ 334.1654 IR spectrum (film) ν (cm ⁻¹ ): 3470, 2977, 1726,
1703, 1404, 1282, 1164, 1109, 994, 720.

Example 16 3- (ε-N′-benzyloxycarbonyl-α-N-
t-Butoxycarbonyl-DL-lysyl) methybenzoate
Le (Compound No. 2-322)

[0248]

Embedded image (16a) ε - N ″-(benzyloxycarbonyl) α
-N '-(t-butoxycarbonyl) -L-lysine N
-Methoxy-N-methylamide ε-N ′-(benzyloxycarbonyl) α-N- (t
-Butoxycarbonyl) -L-lysine (11.41 g,
30 mmol) and reacted in the same manner as in Example 1a,
Purification provided the title compound (12.71 g, 100%) as an oil. NMR spectrum (CDCl ₃ ) δ ppm: 7.36 to 7.30 (5H, m), 5.2
1 (1H, d, J = 8.8), 5.09 (2H, s), 4.87 (1H, brs), 4.66 (1H, b
rs), 3.76 (3H, s), 3.20 (3H, s), 3.20-3.15 (2H, m), 1.73
-1.67 (1H, m), 1.58-1.47 (5H, m), 1.42 (9H, s).

(16b) 3- (ε-N′-benzyloxy)
Cicarbonyl-α-Nt-butoxycarbonyl-L-
1,3-dibromobenzene (0.97 m ) in a nitrogen atmosphere of lysyl) bromobenzene
1,8.0 mmol) of tetrahydrofuran (20 m
1) Add n-butyllithium (6.3 m
1,9.6 mmol) was added. Immediately after dropping ε-N ''
A solution of-(benzyloxycarbonyl) α-N '-(t-butoxycarbonyl) -L-lysine N-methoxy-N-methylamide (0.85 g, 2 mmol) in tetrahydrofuran (10 ml) was added, and the mixture was further added at -78 ° C. Stirred for minutes. After completion of the reaction, saturated aqueous ammonium chloride solution (10
ml), and diluted with ethyl acetate (20 ml). The organic layer was separated and dried over anhydrous sodium sulfate. The concentrated residue was purified by silica gel column chromatography (eluent: 17% ethyl acetate / hexane) to give the title compound (0.98 g, 94%) as white crystals. Melting point: 50.0-52.0 ° C. Specific rotation: [α] ²³ _D = 12.4 (c = 0.57, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 519.1479 calculated value C ₂₅ H ₃₂ N ₂ O ₅ Br 519.1495 IR spectrum (KBr) ν (cm ⁻¹ ): 3352, 1694, 1528,
1247, 1170, 809 NMR spectrum (CDCl ₃ ) δ ppm: 8.09 (1H, s), 7.87 (1H,
d, J = 7.7), 7.72 (1H, d, J = 8.4), 7.39-7.29 (6H, m), 5.46
(1H, d, J = 7.9), 5.26-5.18 (1H, m), 5.08 (2H, s), 4.85 (1
H, brs), 3.16 (2H, d, J = 5.7), 1.88-1.82 (1H, m), 1.56-1.
26 (5H, m), 1.43 (9H, s).

(16c) 3- (ε-N′-benzyloxy)
Cicarbonyl-α-Nt-butoxycarbonyl-DL
-Risyl) methyl benzoate 3- (ε-N′-benzyloxycarbonyl-α-N-
The same reaction as in Example 1c was carried out using t-butoxycarbonyl-L-lysyl) bromobenzene (260 mg, 0.5 mmol), and the title compound (208.6 m) was purified.
g, 84%) as an oil. High-resolution mass spectrum: observed value [M + H] ⁺ 499.2468 calculated value C ₂₇ H ₃₅ N ₂ O ₇ 499.2445 IR spectrum (film) ν (cm ⁻¹ ): 3351, 2950, 1694,
1522, 1367, 1249, 755, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.60 (1H, s), 8.27 (1H,
d, J = 7.9), 8.15 (1H, d, J = 7.9), 7.58 (1H, t, J = 7.9), 7.35
-7.29 (5H, m), 5.52 (1H, d, J = 7.7), 5.35-5.31 (1H, m), 5.
07 (2H, s), 4.88 (1H, brs), 3.95 (3H, s), 3.14 (2H, d, J = 5.
6), 1.91-1.85 (1H, m), 1.60-1.24 (5H, m), 1.44 (9H, s).

Example 17 4- (ε-N′-benzyloxycarbonyl-α-N-
t-Butoxycarbonyl-DL-lysyl) methybenzoate
Le (Compound No. 3-190)

[0252]

Embedded image (17a) 4- (ε-N′-benzyloxycarbonyl
-Α-Nt-butoxycarbonyl-L-lysyl) bromide
Mobenzene 1,4-dibromobenzene (1.89 g, 8.0 mmol
l) and ε-N ″-(benzyloxycarbonyl) α-
N '-(t-butoxycarbonyl) -L-lysine N-
Methoxy-N-methylamide (0.85 g, 2 mmol
Using l), the reaction was carried out in the same manner as in Example 16b, followed by purification to obtain the title compound (1.01 g, 98%) as a white solid. Melting point: 82.5-83.5 ° C. Specific rotation: [α] ²³ _D = 18.6 (c = 0.94, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + Na] ⁺ 541.1295 calculated value C ₂₅ H ₃₁ N ₂ O ₅ BrNa 541.1314 IR spectrum (KBr) ν (cm ⁻¹ ): 3347, 1690, 1523,
1248, 1169 NMR spectrum (CDCl ₃ ) δ ppm: 7.83 (2H, d, J = 8.5), 7.
63 (2H, d, J = 8.4), 7.36-7.31 (5H, m), 5.46 (1H, d, J = 7.9),
5.23-5.18 (1H, m), 5.08 (2H, s), 4.83 (1H, brs), 3.17-3.
13 (2H, m), 1.88-1.82 (1H, m), 1.59-1.26 (5H, m), 1.43 (9
H, s).

(17b) 4- (ε-N′-benzyloxy)
Cicarbonyl-α-Nt-butoxycarbonyl-DL
-Ridyl) methyl benzoate 4- (ε-N′-benzyloxycarbonyl-α-N-
The same reaction as in Example 1c was carried out using t-butoxycarbonyl-L-lysyl) bromobenzene (260 mg, 0.5 mmol), purification was performed, and the title compound (231.8 m
g, 93%) as a white solid. Melting point: 69.0-71.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 499.2462 Calculated value C ₂₇ H ₃₅ N ₂ O ₇ 499.2444 IR spectrum (KBr) ν (cm ⁻¹ ): 3356 , 2936, 1726,
1691, 1522, 1283, 1168, 1110 NMR spectrum (CDCl ₃ ) δ ppm: 8.14 (2H, d, J = 8.5), 8.
01 (2H, d, J = 8.4), 7.36-7.29 (5H, m), 5.48 (1H, d, J = 8.0),
5.30-5.25 (1H, m), 5.08 (2H, s), 4.05 (1H, brs), 3.96 (3
H, s), 3.15 (2H, d, J = 3.9), 1.90-1.85 (1H, m), 1.56-1.28
(5H, m), 1.44 (9H, s).

Example 18 3- (O-benzyl-Nt-butoxycarbonyl-D
Methyl L-tyrosyl) benzoate (Exemplary Compound No. 2-3)
33)

[0255]

Embedded image (18a) O-benzyl-N ′-(t-butoxycarbo
Nyl) -L-tyrosine N-methoxy-N-methylamido O-benzyl-N ′-(t-butoxycarbonyl) -L
Using -tyrosine (22.29 g, 60 mmol), the reaction was carried out in the same manner as in Example 1a, purification was carried out, and the title compound (2
(3.77 g, 96%) as a white solid. NMR spectrum (CDCl ₃ ) δ ppm: 7.43-7.30 (5H, m), 7.0
8 (2H, d, J = 8.8), 6.89 (2H, d, J = 8.1), 5.16 (1H, d, J = 8.1),
5.04 (2H, s), 4.99-4.90 (1H, m), 3.65 (3H, s), 3.16 (3H,
s), 2.99 (1H, dd, J = 5.9,13.9), 2.83 (1H, dd, J = 7.3,13.
2), 1.39 (9H, s).

(18b) 3- (O-benzyl-Nt-
Butoxycarbonyl-L-tyrosyl) bromobenzene 1,3-dibromobenzene (4 ml, 33 mmol) and O-benzyl-N '-(t-butoxycarbonyl)-
L-tyrosine N-methoxy-N-methylamide (4.
The reaction was carried out in the same manner as in Example 1b using 14 g (10 mmol) and purified to give the title compound (4.98 g, 98 mmol).
%) As a white solid. Melting point: 46.0-48.0 ° C. Specific rotation: [α] ²³ _D = 20.2 (c = 0.80, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + Na] ⁺ 532.1074 calculated value C ₂₇ H ₂₈ NO ₄ BrNa 532.1100 IR spectrum (KBr) ν (cm ⁻¹ ): 3352, 1685, 1512,
1367, 1242, 1166, 1024, 738, 697 NMR spectrum (CDCl ₃ ) δ ppm: 8.01 (1H, s), 7.83 (1H,
d, J = 7.9), 7.69 (1H, d, J = 8.3), 7.43-7.30 (6H, m), 6.93
(2H, d, J = 8.5), 6.83 (2H, d, J = 8.4), 5.43-5.39 (1H, m),
5.34 (1H, d, J = 8.2), 5.01 (2H, s), 2.13 (1H, dd, J = 6.4,14.
0), 2.94 (1H, dd, J = 5.5, 13.9), 1.43 (9H, s).

(18c) 3- (O-benzyl-Nt-
Methyl butoxycarbonyl-DL-tyrosyl) benzoate 3- (O-benzyl-Nt-butoxycarbonyl-L
-Tyrosyl) bromobenzene (255 mg, 0.5 mm
ol) and purified in the same manner as in Example 1c, to give the title compound (149.1 mg, 61%) as a white solid. Melting point: 110.0-113.0 ° C. High-resolution mass spectrum: Observed value [M + Na] ⁺ 512.2048 Calculated value C ₂₉ H ₃₁ NO ₆ Na 512.2049 IR spectrum (KBr) ν (cm ⁻¹ ): 3349, 1726, 1683,
1514, 1307, 1238, 1003, 755 NMR spectrum (CDCl ₃ ) δ ppm: 8.54 (1H, s), 8.25 (1H,
d, J = 7.9), 8.10 (1H, d, J = 7.7), 7.55 (1H, t, J = 7.8), 7.42
-7.30 (5H, m), 6.92 (2H, d, J = 8.5), 6.81 (2H, d, J = 8.5),
5.55-5.50 (1H, m), 5.41 (1H, d, J = 8.0), 4.99 (2H, s), 3.9
6 (3H, s), 3.16 (1H, dd, J = 6.3,14.0), 2.95 (1H, dd, J = 5.6,
14.0), 1.44 (9H, s).

Example 19 4- (O-benzyl-Nt-butoxycarbonyl-D
Methyl L-tyrosyl) benzoate (Exemplary Compound No. 3-1)
96)

[0259]

Embedded image (19a) 4- (O-benzyl-Nt-butoxycal
Bonyl-L-tyrosyl) bromobenzene 1,4-dibromobenzene (7.79 g, 33 mmol
l) and O-benzyl-N ′-(t-butoxycarbonyl) -L-tyrosine N-methoxy-N-methylamide (4.14 g, 10 mmol), and the reaction was carried out in the same manner as in Example 1b. To give the title compound (4.72
g, 93%) as a white solid. Melting point: 133.0-136.0 ° C. Specific rotation: [α] ²³ _D = 8.7 (c = 0.47, CHC
l ₃ ) High-resolution mass spectrum: measured value [M + Na] ⁺ 532.1075 calculated value C ₂₇ H ₂₈ NO ₄ BrNa 532.1099 IR spectrum (KBr) ν (cm ⁻¹ ): 3346, 1680, 1585,
1515, 1246, 1165. NMR spectrum (CDCl ₃ ) δ ppm: 7.77 (2H, d, J = 8.6), 7.
60 (2H, d, J = 8.6), 7.42-7.30 (5H, m), 6.91 (2H, J = 8.5),
6.82 (2H, d, J = 8.5), 5.43-5.39 (1H, m), 5.34 (1H, d, J = 8.
1), 5.01 (2H, s), 3.13 (1H, dd, J = 6.3,14.0), 2.92 (1H, d
d, J = 5.6,13.9), 1.43 (9H, s).

(19b) 4- (O-benzyl-Nt-
Methyl butoxycarbonyl-DL-tyrosyl) benzoate 4- (O-benzyl-Nt-butoxycarbonyl-L
-Tyrosyl) bromobenzene (255 mg, 0.5 mm
ol) and purified in the same manner as in Example 1c, to give the title compound (180.4 mg, 74%) as a white solid. Melting point: 122.0-124.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 490.2220 Calculated value C ₂₉ H ₃₂ NO ₆ 490.2229 IR spectrum (KBr) ν (cm ⁻¹ ): 3358, 1720 , 1684,
1513, 1283, 1244, 1168, 1111, 1017 NMR spectrum (CDCl ₃ ) δ ppm: 8.12 (2H, d, J = 8.5), 7.
96 (2H, d, J = 8.2), 7.42-7.30 (5H, m), 6.91 (2H, d, J = 8.5),
6.82 (2H, d, J = 8.5), 5.51-5.46 (1H, m), 5.36 (1H, d, J = 8.
1), 5.00 (2H, s), 3.95 (3H, s), 3.16 (1H, dd, J = 6.3,14.
0), 2.93 (1H, dd, J = 5.7,14.0), 1.43 (9H, s).

Example 20 3- (Nt-butoxycarbonyl-Ot-butyl-
DL-threonyl) methyl benzoate (Exemplary Compound No. 2)
-257)

[0262]

Embedded image (20a) N ′-(t-butoxycarbonyl) -Ot
-Butyl-L-threonine N-methoxy-N-methyl
Amide N- (t-butoxycarbonyl) -Ot-butyl-L
Using threonine (16.52 g, 60 mmol)
The reaction was performed and purified in the same manner as in Example 1a to give the title compound (17.76 g, 93%) as an oil. NMR spectrum (CDCl ₃ ) δ ppm: 5.42 (1H, d, J = 9.5), 4.
44 (1H, dd, J = 2.2,10.3), 4.08 (1H, d, J = 5.1), 3.77 (3H, s),
3.19 (3H, s), 1.45 (9H, s), 1.20 (3H, d, J = 6.6), 1.11 (9H,
s).

(20b) 3- (Nt-butoxycarbo )
Nyl-Ot-butyl-L-threonyl) bromobenze
Using 1,3-dibromobenzene (4 ml, 33 mmol) and N ′-(t-butoxycarbonyl) -Ot-butyl-L-threonine N-methoxy-N-methylamide (3.18 g, 10 mmol). The reaction was carried out in the same manner as in Example 1b, purified and the title compound (4.00 g,
97%) as an oil. Specific rotation: [α] ²³ _D = 61.0 (c = 1.08, CH
Cl ₃ ) High-resolution mass spectrum: Observed value [M + Na] ⁺ 436.1075 Calculated value C ₁₉ H ₂₈ NO ₄ BrNa 436.1099 IR spectrum (film) ν (cm ⁻¹ ): 3437, 2977, 1715,
1498, 1366, 1233, 1171. NMR spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, s), 7.88 (1H,
d, J = 7.7), 7.70 (1H, d, J = 8.1), 7.35 (1H, t, J = 7.9), 5.60
(1H, d, J = 8.6), 5.10 (1H, dd, J = 2.8,8.7), 4.04 (1H, dq, J =
2.8,6.2), 1.45 (9H, s), 1.20 (3H, d, J = 6.5), 1.04 (9H,
s).

(20c) 3- (Nt-butoxycarbo )
Nyl-O-t-butyl-DL-threonyl) benzoic acid
Cyl 3- (Nt-butoxycarbonyl-Ot-butyl-
(L-threonyl) bromobenzene (207 mg, 0.5
The reaction was carried out in the same manner as in Example 1c and purified, to give the title compound (152.5 mg, 77%) as 1.
Obtained as a 4: 1 mixture. High-resolution mass spectrum: measured value [M + Na] ⁺ 416.2058 calculated value C ₂₁ H ₃₁ NO ₆ Na 416.2049 IR spectrum (film) ν (cm ⁻¹ ): 3437, 3378, 2978,
1728, 1500, 1367, 1301, 1212, 1168, 1091, 721.

Example 21 4- (Nt-butoxycarbonyl-Ot-butyl-
DL-threonyl) methyl benzoate (Exemplary Compound No. 3)
-153)

[0266]

Embedded image (21a) 4- (Nt-butoxycarbonyl-Ot
-Butyl -L-threonyl) bromobenzene 1,4-dibromobenzene (7.79 g, 33 mmol
1) and N '-(t-butoxycarbonyl) -Ot-
Example 1b using butyl-L-threonine N-methoxy-N-methylamide (3.18 g, 10 mmol)
The reaction was carried out in the same manner as described above, purified and the title compound (4.02) was purified.
g, 97%) as a white solid. Melting point: 86.5-87.5 ° C. Specific rotation: [α] ²³ _D = 70.8 (c = 1.37, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 414.1278 calculated value C ₁₉ H ₂₉ NO ₄ Br 414.1280 IR spectrum (KBr) ν (cm ⁻¹ ): 3367, 2973, 1695,
1678, 1587, 1522, 1368, 1304, 1245, 1210, 1167, 87
2, 627. NMR spectrum (CDCl ₃ ) δ ppm: 7.83 (2H, d, J = 8.5), 7.
62 (2H, d, J = 8.6), 5.59 (1H, d, J = 8.8), 5.09 (1H, dd, J = 2.
6,8.8), 4.03 (1H, dq, J = 2.6,6.1), 1.46 (9H, s), 1.21 (3
H, d, J = 6.1), 1.04 (9H, s).

(21b) 4- (Nt-butoxycarbo )
Nyl-O-t-butyl-DL-threonyl) benzoic acid
Cyl 4- (Nt-butoxycarbonyl-Ot-butyl-
(L-threonyl) bromobenzene (207 mg, 0.5
The reaction was carried out and purified in the same manner as in Example 1c, and purified using the title compound (153.3 mg, 78%).
Obtained as a 9: 1 mixture. High-resolution mass spectrum: measured value [M + H] ⁺ 394.2261 calculated value C ₂₁ H ₃₂ NO ₆ 394.2229 IR spectrum (film) ν (cm ⁻¹ ): 3438, 2977, 1727,
1499, 1367, 1281, 1170, 1109, 756, 718.

Example 22 3- (N-benzyloxycarbonyl-O-t-butyl
-DL-seryl) methyl benzoate (Exemplified Compound No. 2-
506)

[0269]

Embedded image (22a) N′-benzyloxycarbonyl-Ot-
Butyl-L-serine N-methoxy-N-methylamide N-benzyloxycarbonyl -Ot -butyl-L-
The reaction was carried out in the same manner as in Example 1a using serine (17.72 g, 60 mmol), and the mixture was purified to give the title compound (19.
93g, 98%) as an oil. NMR spectrum (CDCl ₃ ) δ ppm: 7.36 to 7.30 (5H, m), 5.6
2 (1H, d, J = 8.1), 5.13 (1H, d, J = 12.5), 5.08 (1H, d, J = 12.
5), 4.84 (1H, brs), 3.78 (3H, s), 3.63 (1H, dd, J = 4.4,9.
5), 3.57 (1H, dd, J = 5.9,9.5), 3.23 (3H, s), 1.14 (9H,
s).

(22b) 3- (N-benzyloxycal
Bonyl-Ot-butyl-L-seryl) bromobenzene 1,3-dibromobenzene (4 ml, 33 mmol) and N'-benzyloxycarbonyl-Ot-butyl-
L-serine N-methoxy-N-methylamide (3.3
8g, 10mmol), and the reaction was carried out in the same manner as in Example 1b, followed by purification.
%) As an oil. Specific rotation: [α] ²³ _D = 19.0 (c = 1.05, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 434.0943 calculated value C ₂₁ H ₂₅ NO ₄ Br 434.0967 IR spectrum (film) ν (cm ⁻¹ ): 3426, 2975, 1695,
1504, 1215, 1094, 1071, 737, 697. NMR spectrum (CDCl ₃ ) δ ppm: 8.08 (1H, s), 7.85 (1H,
d, J = 7.7), 7.70 (1H, d, J = 8.1), 7.40-7.32 (6H, m), 5.86
(1H, d, J = 7.9), 5.31-5.27 (1H, m), 5.13 (2H, s), 3.71 (1
H, dd, J = 3.8,9.2), 3.63 (1H, dd, J = 4.9,9.1), 0.99 (9H,
s).

(22c) 3- (N-benzyloxycal
Bonyl-O-t-butyl-DL-seryl) methyl benzoate
Le 3- (N- benzyloxycarbonyl -O-t-butyl -L- seryl) bromobenzene (217 mg, 0.5 m
mol)) and purified in the same manner as in Example 1c, and purified to give the title compound (64.2 mg, 31%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 414.1920 calculated value C ₂₃ H ₂₈ NO ₆ 414.1916 IR spectrum (film) ν (cm ⁻¹ ): 3365, 2975, 1727,
1696, 1504, 1302, 1285, 1212, 1100, 724, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.59 (1H, s), 8.26 (1H,
d, J = 7.7), 8.13 (1H, d, J = 7.7), 7.57 (1H, t, J = 7.8), 7.37
-7.31 (5H, m), 5.93 (1H, d, J = 7.8), 5.40 (1H, dt, J = 4.2,8.
1), 5.14 (2H, s), 3.96 (3H, s), 3.74 (1H, dd, J = 3.6,9.4),
3.67 (1H, dd, J = 4.8, 9.1), 0.96 (9H, s).

Example 23 4- (N-benzyloxycarbonyl-O-t-butyl
-DL-seryl) methyl benzoate (Exemplified Compound No. 3-
297)

[0273]

Embedded image (23a) 4- (N-benzyloxycarbonyl-O-
t-butyl-L-seryl) bromobenzene 1,4-dibromobenzene (7.79 g, 33 mmol
l) and N′-benzyloxycarbonyl-Ot-butyl-L-serine N-methoxy-N-methylamide (3.38 g, 10 mmol), the reaction was carried out in the same manner as in Example 1b, followed by purification. The title compound (4.29 g,
99%) as a white solid. Melting point: 72.5-73.0 ° C. Specific rotation: [α] ²³ _D = 25.5 (c = 1.60, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 434.0975 calculated value C ₂₁ H ₂₅ NO ₄ Br 434.0967 IR spectrum (KBr) ν (cm ⁻¹ ): 3351, 2970, 1717,
1685, 1586, 1519, 1241, 1224, 1088, 1076, 1048, 98
4, 835, 697, 585 NMR spectrum (CDCl ₃ ) δ ppm: 7.81 (2H, d, J = 8.4), 7.
61 (2H, d, J = 8.5), 7.37-7.30 (5H, m), 5.87 (1H, d, J = 7.9),
5.30 (1H, dt, J = 4.0,8.3), 5.13 (2H, s), 3.70 (1H, dd, J =
3.8,9.0), 3.64 (1H, dd, J = 4.7,9.2), 0.98 (9H, s).

(23b) 4- (N-benzyloxycal
Bonyl-O-t-butyl-DL-seryl) methyl benzoate
Le 4-(N-benzyloxycarbonyl--O-t-butyl -L- seryl) bromobenzene (217 mg, 0.5 m
mol), and purified in the same manner as in Example 1c, to give the title compound (191.1 mg, 92%) as a white solid. Melting point: 65.5-67.0 ° C High-resolution mass spectrum: Observed value [M + H] ⁺ 414.1934 Calculated value C ₂₃ H ₂₈ NO ₆ 414.1916 IR spectrum (KBr) ν (cm ⁻¹ ): 3365, 2976 , 1719,
1684, 1514, 1283, 1105, 696, 585 NMR spectrum (CDCl ₃ ) δ ppm: 8.13 (2H, d, J = 8.4), 7.
97 (2H, d, J = 8.4), 7.37-7.29 (5H, m), 5.90 (1H, d, J = 8.0),
5.35 (1H, dt, J = 4.0,8.0), 5.13 (2H, s), 3.96 (3H, s), 3.
72 (1H, dd, J = 3.7,9.3), 3.65 (1H, dd, J = 4.5,9.0), 0.95 (9
H, s).

Example 24 3- (N-benzyloxycarbonyl-β-tert-butyl)
-DL-aspartoyl) methyl benzoate (Exemplary Compound No. 2-571)

[0276]

Embedded image (24a) N′-benzyloxycarbonyl-β-t-
Butyl-L-aspartic acid N-methoxy-N-methyl
Luamide N-benzyloxycarbonyl-β-t-butyl-L-
The reaction was carried out in the same manner as in Example 1a using aspartic acid (19.40 g, 60 mmol) and purification was performed to obtain the title compound (21.98 g, 100%) as an oil.
NMR spectrum (CDCl ₃ ) δ ppm: 7.35-7.29 (5H, m), 5.6
5 (1H, d, J = 8.1), 5.13 (1H, d, J = 11.7), 5.08 (1H, d, J = 12.
5), 5.04-5.02 (1H, m), 3.78 (3H, s), 3.22 (3H, s), 2.71 (1
H, dd, J = 5.1,15.4), 2.55 (1H, dd, J = 7.3,14.6), 1.42 (9H,
s).

(24b) 3- (N-benzyloxycal )
Bonyl-β-t-butyl-L-aspartyl) bromo
Benzene 1,3-dibromobenzene (4 ml, 33 mmol) and N′-benzyloxycarbonyl-β-t-butyl-
The reaction was carried out in the same manner as in Example 1b using L-aspartic acid N-methoxy-N-methylamide (3.66 g, 10 mmol), and the mixture was purified to give the title compound (4.38 g,
95%) as an oil. Specific rotation: [α] ²³ _D = 16.1 (c = 1.17, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 462.0915 calculated value C ₂₂ H ₂₅ NO ₅ Br 462.0916 IR spectrum (film) ν (cm ⁻¹ ): 3331, 2979, 1726,
1695, 1503, 1369, 1253, 1218, 1158, 741, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.10 (1H, s), 7.89 (1H,
d, J = 7.8), 7.71 (1H, d, J = 8.1), 7.38-7.31 (6H, m), 5.84
(1H, d, J = 8.7), 5.44 (1H, ddd, J = 5.2,5.5,9.0), 5.13 (2H,
s), 2.86 (1H, dd, J = 5.7,16.0), 2.70 (1H, dd, J = 5.3,16.
0), 1.39 (9H, s).

(24c) 3- (N-benzyloxycal )
Bonyl-β-t-butyl-DL-aspartoyl) repose
Kosan methyl 3- (N- benzyloxycarbonyl-beta-t-butoxy -L- Asuparutoiru) bromobenzene (231m
g, 0.5 mmol), and reacted and purified in the same manner as in Example 1c to give the title compound (165.7 mg, 75 mmol).
%) As an oil. High-resolution mass spectrum: measured value [M + Na] ⁺ 464.1680 calculated value C ₂₄ H ₂₇ NO ₇ Na 464.1885 IR spectrum (film) ν (cm ⁻¹ ): 3349, 1727, 1524,
1302, 1253, 1216, 1158, 756, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.60 (1H, s), 8.26 (1H,
d, J = 7.8), 8.16 (1H, d, J = 7.8), 7.56 (1H, t, J = 7.8), 7.35
-7.30 (5H, m), 5.91 (1H, d, J = 8.5), 5.52 (1H, ddd, J = 5.3,
5.5,8.7), 5.13 (2H, s), 3.95 (3H, s), 2.90 (1H, dd, J = 5.
5,16.0), 2.73 (1H, dd, J = 5.3,16.0), 1.38 (9H, s).

Example 25 4- (N-benzyloxycarbonyl-β-tert-butyl)
-DL-aspartoyl) methyl benzoate (Exemplary Compound No. 3-328)

[0280]

Embedded image (25a) 4- (N-benzyloxycarbonyl-β-
t-Butyl-L-aspartoyl) bromobenzene 1,4-dibromobenzene (7.79 g, 33 mmol)
l) and N′-benzyloxycarbonyl-β-t-butyl-L-aspartic acid N-methoxy-N-methylamide (3.66 g, 10 mmol) using Example 1
The reaction was carried out in the same manner as in step b), purified and the title compound (4.2)
(3 g, 92%) as a white solid. Melting point: 71.
0-74.0 ° C. Specific rotation: [α] ²³ _D = −7.6 (c = 0.61, CH
Cl ₃ ) High-resolution mass spectrum: Observed value [M + Na] ⁺ 484.0732 Calculated value C ₂₂ H ₂₄ NO ₅ BrNa 484.0736 IR spectrum (KBr) ν (cm ⁻¹ ): 3292, 1726, 1687,
1588, 1548, 1301, 1279, 1253, 1160, 1070, 1042, 69
6 NMR spectrum (CDCl ₃ ) δ ppm: 7.84 (2H, d, J = 8.3), 7.
60 (2H, d, J = 8.4), 7.35-7.31 (5H, m), 5.83 (1H, d, J = 8.8),
5.45 (1H, ddd, J = 5.4,5.6,9.0), 5.12 (2H, s), 2.85 (1H, d
d, J = 5.6,16.0), 2.69 (1H, dd, J = 5.4,16.0), 1.39 (9H,
s).

(25b) 4- (N-benzyloxycal
Bonyl-β-t-butyl-DL-aspartoyl) repose
Methyl 4- (N-benzyloxycarbonyl-β-t-butoxy-L-aspartyl) bromobenzene (231 m
g, 0.5 mmol), and reacted and purified in the same manner as in Example 1c to give the title compound (165.4 mg, 75 mmol).
%) As a white solid. Melting point: 49.0-50.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 442.857 Calculated value C ₂₄ H ₂₈ NO ₇ 442.1866 IR spectrum (KBr) ν (cm ⁻¹ ): 3379, 2979 , 1727,
1696, 1520, 1283, 1160, 1112, 1042, 959, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.12 (2H, d, J = 8.3), 8.
00 (2H, d, J = 8.3), 7.35-7.31 (5H, m), 5.88 (1H, d, J = 8.8),
5.49 (1H, ddd, J = 5.3,5.5,8.7), 5.12 (2H, s), 3.96 (3H,
s), 2.87 (1H, dd, J = 5.5,16.1), 2.72 (1H, dd, J = 5.2,16.
1), 1.38 (9H, s).

Example 26 3- (N-benzyloxycarbonyl-γ-t-butyl)
-DL-glutamoyl) methyl benzoate (Exemplary Compound No. 2-579)

[0283]

Embedded image (26a) N′-benzyloxycarbonyl-γ-t-
N-methoxy-N-methyl butyl-L-glutamate
Amide N-benzyloxycarbonyl-γ-t-butyl-L-
Using glutamic acid (20.24 g, 60 mmol)
The reaction was performed and purified in the same manner as in Example 1a to give the title compound (22.43 g, 98%) as an oil. NMR spectrum (CDCl ₃ ) δ ppm: 7.38-7.30 (5H, m), 5.5
4 (1H, d, J = 8.1), 5.12 (1H, d, J = 12.5), 5.07 (1H, d, J = 12.
5), 4.77 (1H, brs), 3.79 (3H, s), 3.21 (3H, s), 2.32 (2H,
t, J = 7.3), 2.07-2.02 (1H, m), 1.90-1.85 (1H, m), 1.43 (9
H, s).

(26b) 3- (N-benzyloxycal
Bonyl-γ-t-butyl-L-glutamoyl) bromobe
Benzene 1,3-dibromobenzene (4 ml, 33 mmol) and N'- benzyloxycarbonyl-gamma-t-butyl -
The reaction was carried out in the same manner as in Example 1b using L-glutamic acid N-methoxy-N-methylamide (3.80 g, 10 mmol), and the mixture was purified to give the title compound (4.63 g,
97%) as an oil. Specific rotation: [α] ²³ _D = 16.8 (c = 1.42, CH
Cl ₃ ) High-resolution mass spectrum: observed value [M + Na] ⁺ 498.0901 calculated value C ₂₃ H ₂₆ NO ₅ BrNa 498.0892 IR spectrum (film) ν (cm ⁻¹ ): 3353, 2978, 1725,
1511, 1368, 1224, 1155, 1057, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.18 (1H, s), 8.00 (1H,
d, J = 7.8), 7.74 (1H, d, J = 8.1), 7.41-7.28 (5H, m), 7.19
(1H, t, J = 7.8), 5.71 (1H, d, J = 8.1), 5.37 (1H, dt, J = 3.5,
8.5), 5.12 (2H, s), 2.44-2.35 (1H, m), 2.31-2.20 (2H,
m), 1.78-1.68 (1H, m), 1.44 (9H, s).

(26c) 3- (N-benzyloxycal
Bonyl-γ-t-butyl-DL-glutamoyl) benzoate
Methyl 3- (N-benzyloxycarbonyl-γ-t-butoxy-L-glutamoyl) bromobenzene (238 mg,
0.5 mmol), and reacted and purified in the same manner as in Example 1c to give the title compound (136.8 mg, 60%).
Was obtained as an oil. High-resolution mass spectrum: measured value [M + Na] ⁺ 478.1830 calculated value C ₂₅ H ₂₉ NO ₇ Na 478.1842 IR spectrum (film) ν (cm ⁻¹ ): 3353, 2978, 1726,
1522, 1368, 1286, 1256, 1219, 1155, 699 NMR spectrum (CDCl ₃ ) δ ppm: 8.68 (1H, s), 8.29 (1H,
d, J = 7.6), 8.25 (1H, d, J = 7.8), 7.61 (1H, t, J = 7.8), 7.39
-7.32 (5H, m), 5.78 (1H, d, J = 8.0), 5.46 (1H, dt, J = 3.0,8.
1), 5.13 (2H, s), 3.97 (3H, s), 2.44-2.36 (1H, m), 2.31-
2.01 (2H, m), 1.81-1.73 (1H, m), 1.43 (9H, s).

Example 27 4- (N-benzyloxycarbonyl-γ-t-butyl)
-DL-glutamoyl) methyl benzoate (Exemplary Compound No. 3-341)

[0287]

Embedded image (27a) 4- (N-benzyloxycarbonyl-γ-
t-Butyl-L-glutamoyl) bromobenzene 1,4-dibromobenzene (7.79 g, 33 mmol)
l) and N′-benzyloxycarbonyl-γ-t-butyl-L-glutamic acid N-methoxy-N-methylamide (3.80 g, 10 mmol), Example 1b
The reaction was carried out in the same manner as described above, purified and the title compound (4.08)
g, 86%) as a white solid. Specific rotation: [α] ²³ _D = 31.5 (c = 1.25, CH
Cl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 476.10075 calculated value C ₂₃ H ₂₇ NO ₅ Br 476.1073 IR spectrum (film) ν (cm ⁻¹ ): 3351, 2978, 1725,
1688, 1587, 1509, 1399, 1368, 1226, 1155, 1071, 8
44, 698 NMR spectrum (CDCl ₃ ) δ ppm: 7.94 (2H, d, J = 8.3), 7.
65 (2H, d, J = 8.4), 7.38-7.30 (5H, m), 5.70 (1H, d, J = 8.1),
5.37 (1H, dt, J = 3.3,8.7), 5.13 (1H, d, J = 12.3), 5.10 (1
H, d, J = 12.3), 2.44-2.34 (1H, m), 2.31-2.19 (2H, m), 1.7
6-1.66 (1H, m), 1.44 (9H, s).

(27b) 4- (N-benzyloxycal
Bonyl-γ-t-butyl-DL-glutamoyl) benzoate
Methyl 4- (N-benzyloxycarbonyl-γ-t-butyl-L-glutamoyl) bromobenzene (238 mg,
0.5 mmol) and purified in the same manner as in Example 1c, followed by purification to give the title compound (180.6 mg, 79%).
Was obtained as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 456.2041 calculated value C ₂₅ H ₃₀ NO ₇ 456.2022 IR spectrum (film) ν (cm ⁻¹ ): 3354, 1726, 1523,
1504, 1368, 1282, 1226, 1155, 1109 NMR spectrum (CDCl ₃ ) δ ppm: 8.16 (2H, d, J = 8.7), 8.
12 (2H, d, J = 8.3), 7.37-7.28 (5H, m), 5.73 (1H, d, J = 8.1),
5.43 (1H, dt, J = 3.3,8.5), 5.14 (1H, d, J = 12.4), 5.10 (1
H, d, J = 12.3), 3.96 (3H, s), 2.45-2.37 (1H, m), 2.33-2.2
0 (2H, m), 1.78-1.70 (1H, m), 1.44 (9H, s).

Example 28 3- (N-benzyloxycarbonyl-DL-trypto
Phil) Methyl benzoate (Exemplary Compound No. 2-489)

[0290]

Embedded image (28a) N '-(benzyloxycarbonyl) -L-
Example 1a using tryptophan N-methoxy-N-methylamide N- (benzyloxycarbonyl) -L-tryptophan (20.30 g, 60 mmol).
And purified to give the title compound (22.48).
g, 98%) as a white solid. NMR spectrum (CDCl ₃ ) δ ppm: 8.06 (1H, s), 7.58 (1H,
d, J = 7.3), 7.34-7.26 (6H, m), 7.18 (1H, t, J = 8.1), 7.10
(1H, t, J = 8.0), 7.00 (1H, s), 5.50 (1H, d, J = 8.1), 5.09 (1
H, d, J = 12.5), 5.03 (1H, d, J = 12.5), 3.67 (3H, s), 3.26 (1
H, dd, J = 5.9,14.6), 3.16 (3H, s), 3.13 (1H, dd, J = 7.3,14.
6).

(28b) 3- (N-benzyloxycal
Bonyl-L-tryptofil) bromobenzene 1,3-dibromobenzene (5.3 ml, 44 mmol
l) and N '-(benzyloxycarbonyl) -L-tryptophan N-methoxy-N-methylamide (3.
81g, 10mmol), and reacted and purified in the same manner as in Example 16b to give the title compound (4.77g, 100mmol).
%) As a white solid. Melting point: 108.0-111.0 ° C. Specific rotation: [α] ²³ _D = 77.5 (c = 0.92, CH
Cl ₃ ) High-resolution mass spectrum: observed value [M + Na] ⁺ 499.0622 calculated value C ₂₅ H ₂₁ N ₂ O ₃ BrNa 499.0633 IR spectrum (KBr) ν (cm ⁻¹ ): 3422, 3278, 1677,
1541, 1457, 1422, 1337, 1290, 1266, 1249, 1219, 74
4,703 NMR spectrum (CDCl ₃ ) δ ppm: 7.97 (1H, s), 7.93 (1H,
s), 7.77 (1H, d, J = 7.8), 7.66 (1H, d, J = 7.1), 7.42 (1H, d, J
= 7.9), 7.35-7.21 (7H, m), 7.16 (1H, t, J = 7.7), 7.05 (1H,
t, J = 7.3), 6.78 (1H, s), 5.72 (1H, d, J = 7.9), 5.63-5.58
(1H, m), 5.15 (1H, d, J = 12.3), 5.10 (1H, d, J = 12.3), 3.38
(1H, dd, J = 6.5,14.8), 3.25 (1H, dd, J = 5.2,14.8).

(28c) 3- (N-benzyloxycal )
Bonyl-DL-tryptofil) methyl benzoate 3- (N-benzyloxycarbonyl-L-tryptophyl) bromobenzene (239 mg, 0.5 mmol)
And purified in the same manner as in Example 1c to give the title compound (186.8 mg, 82%) as a white solid. Melting point: 80.0-82.0 ° C High-resolution mass spectrum: Observed value [M + Na] ⁺ 479.1553 Calculated value C ₂₇ H ₂₄ N ₂ O ₅ Na 479.1583 IR spectrum (KBr) ν (cm ^-1 ): 3331, 1724, 1683,
1521, 1305, 1225, 740,696 NMR spectrum (CDCl ₃ ) δ ppm: 8.48 (1H, s), 8.20 (1H,
d, J = 7.9), 8.02 (1H, d, J = 7.9), 7.98 (1H, s), 7.47 (1H, t,
J = 7.9), 7.43 (1H, d, J = 7.9), 7.38-7.30 (5H, m), 7.26 (1
H, d, J = 8.2), 7.14 (1H, t, J = 7.7), 7.03 (1H, t, J = 7.7), 6.
73 (1H, s), 5.81 (1H, d, J = 7.9), 5.73-5.68 (1H, m), 5.16
(1H, d, J = 12.2), 5.11 (1H, d, J = 12.3), 3.91 (3H, s), 3.39
(1H, dd, J = 6.6,14.8), 3.27 (1H, dd, J = 5.2,14.8).

Example 29 4- (N-benzyloxycarbonyl-DL-trypto
Phil) Methyl benzoate (Exemplary Compound No. 3-285)

[0294]

Embedded image (29a) 4- (N-benzyloxycarbonyl-L-
Tryptofil) bromobenzene 1,4-dibromobenzene (10.38 g, 44 mmol
l) and N '-(benzyloxycarbonyl) -L-tryptophan N-methoxy-N-methylamide (3.
81g, 10mmol), and reacted and purified in the same manner as in Example 16b to give the title compound (4.77g, 100mmol).
%) As a white solid. Melting point: 114.0-117.0 ° C. Specific rotation: [α] ²³ _D = 65.6 (c = 1.29, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + Na] ⁺ 499.0637 calculated value C ₂₅ H ₂₁ N ₂ O ₃ BrNa 499.0633 IR spectrum (KBr) ν (cm ⁻¹ ): 3400, 1682, 1586,
1507, 1456, 1399, 1344, 1230, 1071, 742, 697 NMR spectrum (CDCl ₃ ) δ ppm: 7.92 (1H, s), 7.72 (2H,
d, J = 8.6), 7.54 (2H, d, J = 8.4), 7.41 (1H, d, J = 7.9), 7.38
-7.32 (5H, m), 7.30 (1, d, J = 8.3), 7.16 (1H, t, J = 7.6), 7.
04 (1H, t, J = 7.5), 6.77 (1H, s), 5.72 (1H, d, J = 8.0), 5.63
-5.60 (1H, m), 5.15 (1H, d, J = 12.0), 5.10 (1H, d, J = 12.3),
3.39 (1H, dd, J = 6.5,14.8), 3.24 (1H, dd, J = 5.2,14.8).

(29b) 4- (N-benzyloxycal
Methyl 4- (N-benzyloxycarbonyl-L-tryptophyl) bromobenzene (239 mg, 0.5 mmol)
And purified in the same manner as in Example 1c to give the title compound (197.3 mg, 87%) as a white solid. Melting point: 124.0-125.0 ° C. High-resolution mass spectrum: observed value [M + H] ⁺ 457.1755 calculated value C ₂₇ H ₂₅ N ₂ O ₅ 457.1773 IR spectrum (KBr) ν (cm ⁻¹ ): 3415 , 3346, 1724,
1686, 1529, 1285, 1110, 1058, 742 NMR spectrum (CDCl ₃ ) δ ppm: 8.05 (2H, d, J = 8.2), 7.
95 (1H, s), 7.91 (2H, d, J = 8.4), 7.39 (1H, d, J = 7.9), 7.35
-7.30 (5H, m), 7.28 (1, d, J = 8.1), 7.15 (1H, t, J = 7.7), 7.
03 (1H, t, J = 7.6), 6.76 (1H, s), 5.75 (1H, d, J = 8.0), 5.69
-5.65 (1H, m), 5.16 (1H, d, J = 12.3), 5.10 (1H, d, J = 12.3),
3.95 (3H, s), 3.41 (1H, dd, J = 6.3,14.8), 3.25 (1H, dd, J =
5.1, 14.8).

Example 30 3- (Nt-butoxycarbonyl-DL-leucyl)
4-methoxybenzyl benzoate (Exemplary Compound No. 2-
144)

[0297]

Embedded image (30a) 3- (Nt-butoxycarbonyl-DL-
Benzyl ( leucyl) benzoate 3- (Nt-butoxycarbonyl-L-leucyl) bromobenzene (185 mg, 0.5 mmol) and benzyl alcohol (103 μl, 1.0 mmol) were reacted in the same manner as in Example 1c. Purification provided the title compound (140.7 mg, 66%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 426.2286 calculated value C ₂₅ H ₃₂ NO ₅ 426.2280 IR spectrum (film) ν (cm ⁻¹ ): 3370, 2960, 1723,
1693, 1501, 1368, 1285, 1165, 1117, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.65 (1H, s), 8.29 (1H,
d, J = 7.9), 8.18 (1H, d, J = 7.8), 7.58 (1H, t, J = 7.8), 7.47
-7.35 (5H, m), 5.42 (1H, d, J = 12.3), 5.37 (1H, d, J = 12.4),
5.37-5.31 (1H, m), 5.27 (1H, d, J = 8.7), 1.86-1.76 (1H, m
m), 1.61-1.52 (1H, m), 1.47-1.36 (1H, m), 1.44 (9H, s),
1.05 (3H, d, J = 6.5), 0.89 (3H, d, J = 6.7).

(30b) 3- (Nt-butoxycarbo )
4-methoxybenzyl 3- (Nt-butoxycarbonyl-L-leucyl) bromobenzene (185 mg, 0.5 mmol)
Methoxybenzyl alcohol (125 μl, 1.0 mm
ol) and purified in the same manner as in Example 1c, and purified to give the title compound (120.0 mg, 53%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 456.2393 calculated value C ₂₆ H ₃₄ NO ₆ 456.2386 IR spectrum (film) ν (cm ⁻¹ ): 3369, 2959, 1721,
1693, 1516, 1368, 1250, 1173, 1114, 1035, 824, 76
6, 714 NMR spectrum (CDCl ₃ ) δppm: 8.63 (1H, s), 8.27 (1H,
d, J = 7.9), 8.17 (1H, d, J = 7.7), 7.57 (1H, t, J = 7.8), 7.40
(2H, d, J = 8.7), 6.92 (2H, d, J = 8.7), 5.35 (1H, d, J = 11.8),
5.30 (1H, d, J = 12.2), 5.36-5.26 (2H, m), 3.82 (3H, s) 1.8
5-1.75 (1H, m), 1.58-1.52 (1H, m), 1.49-1.36 (1H, m), 1.
44 (9H, s), 1.05 (3H, d, J = 6.4), 0.88 (3H, d, J = 6.7).

Example 31 3- (N'-tert-butoxycarbonyl-DL-araani
) -N-methylbenzamide (Exemplary Compound No. 2-7
4)

[0300]

Embedded image Palladium (II) chloride (9 m) was added to a benzene solution (10 ml) of 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol).
g, 0.05 mmol), 1,3-bis (diphenylphosphino) propane (41 mg, 0.1 mmol),
1,8-Diazabicyclo (5.4.0) -7-undecene (75 μl, 0.5 mmol) and 40% aqueous methylamine solution (1 ml) were added, and carbon monoxide was applied under pressure (30 atm) at 120 ° C. for 7 hours. Reacted. After completion of the reaction, the reaction solution is concentrated, and the concentrated residue is subjected to silica gel column chromatography (elution solvent: 17% ethyl acetate / hexane to 50%).
% Ethyl acetate / hexane) to give the title compound (6
2.0 mg, 41%) as an oil. High-resolution mass spectrum: measured value [M + Na] ⁺ 329.1489 calculated value C ₁₆ H ₂₂ N ₂ O ₄ Na 329.1477 IR spectrum (film) ν (cm ⁻¹ ): 3330, 2980, 1688,
1544, 1368, 1235, 1167, 756 NMR spectrum (CDCl ₃ ) δ ppm: 8.35 (1H, s), 8.09 (1H,
d, J = 5.3), 8.08 (1H, d, J = 7.3), 7.57 (1H, t, J = 7.7), 6.58
(1H, brs), 5.46 (1H, d, J = 7.7), 5.31 (1H, dq, J = 7.1,7.1),
3.03 (3H, d, J = 4.6), 1.45 (9H, s), 1.40 (3H, d, J = 6.9).

Example 32 3- (N'-tert-butoxycarbonyl-DL-alani
Ru) -N-butylbenzamide (Exemplary compound number 2-7
7)

[0302]

Embedded image Palladium (II) chloride (9 m) was added to a benzene solution (10 ml) of 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol).
g, 0.05 mmol), 1,3-bis (diphenylphosphino) propane (41 mg, 0.1 mmol),
1,8-Diazabicyclo (5.4.0) -7-undecene (75 μl, 0.5 mmol) and n-butylamine (100 μl, 1.0 mmol) were added, and the mixture was heated at 120 ° C. under carbon monoxide pressure (30 atm). The reaction was performed for 7 hours. After completion of the reaction, the reaction solution was concentrated, and the concentrated residue was purified by silica gel column chromatography (eluent: 17% ethyl acetate / hexane) to give the title compound (81.7 mg, 47).
%) As a white solid. Melting point: 86.0-88.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 349.2117 Calculated value C ₁₉ H ₂₉ N ₂ O ₄ 349.2127 IR spectrum (KBr) ν (cm ⁻¹ ): 3314 , 2962, 2933,
1678, 1638, 1541, 1367, 1231, 1171, 718, 690 NMR spectrum (CDCl ₃ ) δ ppm: 8.35 (1H, s), 8.08 (2H,
d, J = 7.7), 7.57 (1H, t, J = 7.7), 6.41 (1H, brs), 5.45 (1H,
d, J = 7.7), 5.31 (1H, dq, J = 7.1,7.1), 3.48 (2H, dd, J = 7.1,
13.1), 1.67-1.59 (2H, m), 1.48-1.39 (2H, m), 1.45 (9H,
s), 1.40 (3H, d, J = 7.2), 0.97 (3H, t, J = 7.3).

Example 33 3- [3- (Nt-butoxycarbonyl-DL-ara
Nyl) benzoylamino] ethyl benzoate (Exemplary Compound No. 2-87)

[0304]

Embedded image 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol) and 3-
Ethyl aminobenzoate (149 μl, 1.0 mmol)
And purified in the same manner as in Example 32 to obtain the title compound (142.7 mg, 65%) as a white solid. High-resolution mass spectrum: measured value [M + Na] ⁺ 463.1833 calculated value C ₂₄ H ₂₈ N ₂ O ₆ Na 463.1845 IR spectrum (KBr) ν (cm ⁻¹ ): 3346, 2980, 1690,
1597, 1546, 1489, 1441, 1368, 1290, 1167, 757 NMR spectrum (CDCl ₃ ) δ ppm: 8.61 (1H, s), 8.58 (1H,
s), 8.24 (1H, s), 8.20 (1H, d, J = 7.8), 8.12 (2H, d, J = 7.
9), 7.84 (1H, d, J = 7.8), 7.61 (1H, t, J = 7.8), 7.46 (1H, t,
J = 8.0), 5.40 (1H, d, J = 8.2), 5.34 (1H, dq, J = 7.0,7.0),
4.38 (2H, q, J = 7.3), 1.43 (9H, s), 1.40 (3H, t, J = 6.9).

Example 34 4- [3- (Nt-butoxycarbonyl-DL-ara
Nyl) benzoylamino] methyl benzoate (Exemplified Compound No. 2-89)

[0306]

Embedded image 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol) and 4-
Methyl aminobenzoate (151 mg, 1.0 mmol)
And purified in the same manner as in Example 32 to obtain the title compound (150.0 mg, 70%) as a white solid. Melting point: 125.0-129.0 ° C. High-resolution mass spectrum: Observed value [M + Na] ⁺ 449.1674 Calculated value C ₂₃ H ₂₆ N ₂ O ₆ Na 449.1689 IR spectrum (KBr) ν (cm ⁻¹ ): 3341, 2980, 1686,
1601, 1529, 1437, 1407, 1368, 1283, 1176, 1112, 85
7,772 NMR spectrum (CDCl ₃ ) δ ppm: 8.68 (1H, s), 8.60 (1H,
s), 8.17 (1H, d, J = 7.7), 8.12 (1H, d, J = 7.9), 8.05 (2H, d, J
= 8.7), 7.84 (2H, d, J = 8.6), 7.62 (1H, t, J = 7.9), 5.35-5.2
9 (2H, m), 3.92 (3H, s), 1.42 (12H, s).

Example 35 2- [3- (Nt-butoxycarbonyl-DL-ara
Nyl) benzoylamino] methyl benzoate (Exemplified Compound No. 2-83)

[0308]

Embedded image 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol) and 2-
Ethyl aminobenzoate (129 μl, 1.0 mmol)
And purified in the same manner as in Example 32 to give the title compound (83.5 mg, 39%) as a white solid. Melting point: 113.0-115.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 427.1862 Calculated value C ₂₃ H ₂₇ N ₂ O ₆ 427.1869 IR spectrum (KBr) ν (cm ⁻¹ ): 3315 , 2980, 1684,
1608, 1590, 1531, 1449, 1299, 1275, 1167, 1085, 75
6,721 NMR spectrum (CDCl ₃ ) δ ppm: 12.21 (1H, s), 8.91 (1
H, d, J = 8.0), 8.68 (1H, s), 8.27 (1H, d, J = 8.0), 8.18 (1H,
d, J = 7.8), 8.11 (1H, d, J = 8.0), 7.67 (1H, t, J = 7.8), 7.63
(1H, t, J = 7.9), 7.16 (1H, t, J = 7.8), 5.59 (1H, d, J = 7.3),
5.38 (1H, dq, J = 7.0,7.0), 3.99 (3H, s), 1.46 (12H, s).

Example 36 3- (N'-tert-butoxycarbonyl-DL-araani
) -N-benzylbenzamide (Exemplary Compound No. 2-
91)

[0310]

Embedded image Using 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol) and benzylamine (109 μl, 1.0 mmol), reacted in the same manner as in Example 32, purified, and Compound (6
9.5 mg, 36%) as a white solid. Melting point: 80.0-83.0 ° C. High-resolution mass spectrum: observed value [M + Na] ⁺ 405.1810 calculated value C ₂₂ H ₂₆ N ₂ O ₄ Na 405.1790 IR spectrum (KBr) ν (cm ⁻¹ ): 3285, 2979, 1689,
1655, 1530, 1455, 1367, 1230, 1167, 697 NMR spectrum (CDCl ₃ ) δ ppm: 8.38 (1H, s), 8.11 (1H,
d, J = 7.9), 8.08 (1H, d, J = 8.0), 7.57 (1H, t, J = 7.8), 7.38
-7.29 (5H, m), 6.74 (1H, brs), 5.43 (1H, d, J = 7.7), 5.29 (1
H, dq, J = 7.2,7.2), 4.68 (1H, d, J = 14.9), 4.64 (1H, d, J = 1
5.7), 1.42 (9H, s), 1.38 (3H, d, J = 7.2) Example 37 3- (N'-t-butoxycarbonyl-DL-araani)
) -N-pyrrolidylbenzamide (Exemplary Compound No. 2
-79)

[0311]

Embedded image Example 3 using 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol) and pyrrolidine (83 μl, 1.0 mmol).
Reaction and purification were carried out in the same manner as in Example 2 to give the title compound (76.9).
mg, 44%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 347.1977 calculated value C ₁₉ H ₂₇ N ₂ O ₄ 347.1971 IR spectrum (film) ν (cm ⁻¹ ): 3311, 2979, 1691,
1623, 1499, 1446, 1367, 1249, 1166, 755 NMR spectrum (CDCl ₃ ) δ ppm: 8.12 (1H, s), 8.02 (1H,
d, J = 7.9), 7.77 (1H, d, J = 7.6), 7.55 (1H, t, J = 7.7), 5.53
(1H, d, J = 7.4), 5.28 (1H, dq, J = 7.2,7.2), 3.67 (2H, t, J =
7.0), 3.43 (2H, t, J = 6.6), 2.03-1.96 (2H, m), 1.94-1.87
(2H, m), 1.46 (9H, s), 1.40 (3H, d, J = 7.2).

Example 38 3- (N'-tert-butoxycarbonyl-DL-alani
Ru) -N, N-dibutylbenzamide (Exemplary Compound No. 2-78)

[0313]

Embedded image 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol) and di-n
The reaction was carried out in the same manner as in Example 32 using -butylamine (169 µl, 1.0 mmol) and purification was performed to obtain the title compound (100.5 mg, 50%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 405.2644 calculated value C ₂₃ H ₃₇ N ₂ O ₄ 405.2753 IR spectrum (film) ν (cm ⁻¹ ): 3324, 2962, 1693,
1632, 1493, 1454, 1367, 1248, 1218, 1165, 731 NMR spectrum (CDCl ₃ ) δ ppm: 7.99 (1H, d, J = 7.8), 7.
95 (1H, s), 7.60 (1H, d, J = 7.9), 7.53 (1H, t, J = 7.6), 5.51
(1H, d, J = 7.4), 5.28 (1H, dq, J = 7.2,7.2), 3.50 (2H, d, J =
6.0), 3.17 (2H, brs), 1.66-1.58 (2H, m), 1.56-1.38 (4H,
m), 1.46 (9H, s), 1.39 (3H, d, J = 6.9), 1.20-1.12 (2H, m),
0.99 (3H, t, J = 6.8), 0.78 (3H, t, J = 6.7).

Example 39 3- (N'-tert-butoxycarbonyl-DL-alani
Ru) -N, N-dimethylbenzamide (Exemplary Compound No. 2-75)

[0315]

Embedded image 3- (Nt-butoxycarbonyl-L-alanyl) bromobenzene (164 mg, 0.5 mmol) and 50
Example 31 using a 1% aqueous solution of dimethylamine (1 ml).
And purified, to give the title compound (19.1 m
g, 12%) as a white solid. Melting point: 90.0-91.0 ° C High-resolution mass spectrum: Observed value [M + H] ⁺ 321.1810 Calculated value C ₁₇ H ₂₅ N ₂ O ₄ 321.1814 IR spectrum (KBr) ν (cm ⁻¹ ): 3341 , 1686, 1618,
1529, 1393, 1367, 1250, 1167 NMR spectrum (CDCl ₃ ) δ ppm: 8.02 (1H, s), 8.01 (1H,
d, J = 7.2), 7.67 (1H, d, J = 7.9), 7.55 (1H, t, J = 7.8), 5.51
(1H, d, J = 7.4), 5.28 (1H, dq, J = 7.2,7.2), 3.14 (3H, s),
2.99 (3H, s), 1.46 (9H, s), 1.40 (3H, d, J = 7.2).

Example 40 3- (Nt-butoxycarbonyl-DL-alanyl)
Methyl 2-methylbenzoate (Exemplary Compound No. 2-11
2)

[0317]

Embedded image (40a) 3- (Nt-butoxycarbonyl- LA)
Ranyl) -2-methylbromobenzene 2,6-dibromotoluene (8.24 g, 33 mmol
1) and N ′-(t-butoxycarbonyl) -L-alanine N-methoxy-N-methylamide (2.32 g,
Using 10 mmol), the reaction was carried out in the same manner as in Example 1b, followed by purification to obtain the title compound (3.42 g, 100%) as an oil. Specific rotation: [α] ²³ _D = 16.7 (c = 1.24, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 342.0708 calculated value C ₁₅ H ₂₁ NO ₃ Br 342.0705 IR spectrum (film) ν (cm ⁻¹ ): 3354, 2978, 1699,
1499, 1447, 1368, 1237, 1169, 1055, 966, 862, 79
3, 738 NMR spectrum (CDCl ₃ ) δ ppm: 7.68 (1H, d, J = 7.5), 7.
52 (1H, d, J = 7.6), 7.14 (1H, t, J = 7.8), 5.38 (1H, d, J = 6.
8), 4.97 (1H, dq, J = 7.3,7.3), 2.43 (3H, s), 1.46 (9H, s),
1.27 (3H, d, J = 7.3).

(40b) 3- (Nt-butoxycarbo )
Nyl-DL-alanyl) -2-methyl benzoate 3- (Nt-butoxycarbonyl-L-alanyl)-
2-methylbromobenzene (171 mg, 0.5 mmol
Using l), the reaction was carried out in the same manner as in Example 1c, purified, and
The title compound (78.4 mg, 49%) was obtained as a white solid. Melting point: 87.0-88.5 ° C. High-resolution mass spectrum: Observed value [M + Na] ⁺ 344.1481 Calculated value C ₁₇ H ₂₃ NO ₅ Na 344.1474 IR spectrum (KBr) ν (cm ⁻¹ ): 3349, 2979, 1723,
1692, 1582, 1513, 1299, 1268, 1237, 1210, 1167, 11
51 NMR spectrum (CDCl ₃ ) δ ppm: 7.90 (1H, d, J = 8.0), 7.
67 (1H, d, J = 7.6), 7.33 (1H, t, J = 7.7), 5.39 (1H, d, J = 7.
0), 5.00 (1H, dq, J = 7.3,7.3), 3.92 (3H, s), 2.53 (3H, s),
1.46 (9H, s), 1.28 (3H, d, J = 7.2).

Example 41 6- (Nt-butoxycarbonyl-DL-alanyl)
Methyl pyridine-2-carboxylate (Exemplary Compound No. 8-
138)

[0320]

Embedded image (41a) 6- (Nt-butoxycarbonyl- LA)
Ranyl) -2-bromopyridine 2,6-dibromopyridine (7.82 g, 33 mmol)
1) and N ′-(t-butoxycarbonyl) -L-alanine N-methoxy-N-methylamide (2.32 g,
Using 10 mmol), the reaction was carried out in the same manner as in Example 1b, followed by purification to obtain the title compound (2.57 g, 78%) as a white solid. Melting point: 78.0-79.0 ° C. Specific rotation: [α] ²³ _D = 42.4 (c = 1.16, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 329.0504 calculated value C ₁₃ H ₁₈ N ₂ O ₃ Br 329.0501 IR spectrum (KBr) ν (cm ⁻¹ ): 3382, 2976, 1698,
1529, 1177, 1121, 985,830, 750 NMR spectrum (CDCl ₃ ) δ ppm: 8.02 (1H, d, J = 7.3), 7.
71 (1H, t, J = 7.9), 7.68 (1H, d, J = 8.0), 5.64 (1H, t, J = 7.
0), 5.36 (1H, brs), 1.46 (3H, d, J = 6.9), 1.45 (9H, s).

(41b) 6- (Nt-butoxycarbo )
Nyl-DL-alanyl) pyridine-2-carboxylic acid methyl
Le 6- (N-t-butoxycarbonyl -L- alanyl) -
The reaction was carried out in the same manner as in Example 1c using 2-bromopyridine (165 mg, 0.5 mmol), and purification was performed to obtain the title compound (154.2 mg, 100%) as a white solid. Melting point: 80.5-82.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 309.1467 Calculated value C ₁₅ H ₂₁ N ₂ O ₅ 309.1450 IR spectrum (KBr) ν (cm ⁻¹ ): 3364 , 2980, 1723,
1692, 1512, 1319, 1175, 1135, 995, 948 NMR spectrum (CDCl ₃ ) δ ppm: 8.29 (1H, d, J = 8.0), 8.
22 (1H, d, J = 8.5), 8.01 (1H, t, J = 7.9), 5.74 (1H, t, J = 6.
5), 5.52 (1H, brs), 4.02 (3H, s), 1.49 (3H, d, J = 7.3), 1.
45 (9H, s).

Example 42 4- (Nt-butoxycarbonyl-DL-alanyl)
Methyl-2,5-dimethylbenzoate (Exemplary Compound No. 3
-66)

[0323]

Embedded image (42a) 4- (Nt-butoxycarbonyl- LA)
Ranyl) -2,5-dimethylbromobenzene 2,5-dibromo-p-xylene (8.71 g, 33 m
mol) and N '-(t-butoxycarbonyl) -L-
Alanine N-methoxy-N-methylamide (2.32
g, 10 mmol) and purified in the same manner as in Example 1b, followed by purification to give the title compound (3.56 g, 100%).
Was obtained as an oil. Specific rotation: [α] ²³ _D = 13.7 (c = 2.01, CH
Cl ₃ ) High-resolution mass spectrum: Observed value [M + H] ⁺ 356.0871 Calculated value C ₁₆ H ₂₃ NO ₃ Br 356.0861 IR spectrum (film) ν (cm ⁻¹ ): 3352, 2978, 2931,
1692, 1498, 1452, 1367, 1247, 1166, 1044, 983, 85
7 NMR spectrum (CDCl ₃ ) δ ppm: 7.52 (1H, s), 7.46 (1H,
s), 5.46 (1H, d, J = 7.1), 5.08 (1H, dq, J = 7.3,7.3), 2.40 (3
H, s), 2.39 (3H, s), 1.46 (9H, s), 1.27 (3H, d, J = 7.2).

(42b) 4- (Nt-butoxycarbo )
Nyl-DL-alanyl) -2,5-dimethylbenzoic acid
The reaction was carried out in the same manner as in Example 1c using tyl 4- (Nt-butoxycarbonyl-L-alanyl) -2,5-dimethylbromobenzene (178 mg, 0.5 mmol), and the title compound (13) was purified.
3.1 mg, 79%) as an oil. High-resolution mass spectrum: measured value [M + Na] ⁺ 358.1438 calculated value C ₁₈ H ₂₅ NO ₅ Na 358.1630 IR spectrum (KBr) ν (cm ⁻¹ ): 3377, 2978, 1700,
1497, 1453, 1368, 1265, 1241, 1170, 1057, 860, 787 NMR spectrum (CDCl ₃ ) δ ppm: 7.78 (1H, s), 7.48 (1H,
s), 5.44 (1H, d, J = 7.1), 5.08 (1H, dq, J = 7.2,7.2), 3.91 (3
H, s), 2.58 (3H, s), 2.41 (3H, s), 1.47 (9H, s), 1.28 (3H, s
d, J = 7.2).

Example 43 5- (Nt-butoxycarbonyl-DL-alanyl)
Methyl thiophene-2-carboxylate (Exemplary Compound No. 8
-20)

[0326]

Embedded image (43a) 5- (Nt-butoxycarbonyl- LA)
Ranyl) -2-bromothiophene 2,5-dibromothiophene (3.7 ml, 33 mmol
1) and N ′-(t-butoxycarbonyl) -L-alanine N-methoxy-N-methylamide (2.32 g,
Using 10 mmol), the reaction was carried out in the same manner as in Example 1b, followed by purification to obtain the title compound (1.47 g, 44%) as a white solid. Melting point: 116.0-117.0 ° C. Specific rotation: [α] ²³ _D = −9.0 (c = 0.95, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 334.0120 calculated value C ₁₂ H ₁₇ NO ₃ BrS 334.0113 IR spectrum (KBr) ν (cm ⁻¹ ): 3348,1703, 1667, 1
534, 1413, 1237, 1178, 1060 NMR spectrum (CDCl ₃ ) δ ppm: 7.57 (1H, d, J = 3.9), 7.
13 (1H, d, J = 4.3), 5.34 (1H, t, J = 7.1), 5.03 (1H, dq, J = 7.
2,7.2), 1.44 (9H, s), 1.43 (3H, d, J = 6.8).

(43b) 5- (Nt-butoxycarbo )
Nyl-DL-alanyl) thiophene-2-carboxylic acid
Tyl 5- (Nt-butoxycarbonyl-L-alanyl)-
2-bromothiophene (167 mg, 0.5 mmol)
And purified in the same manner as in Example 1c to give the title compound (137.9 mg, 88%) as a white solid. Melting point: 108.0-109.0 ° C. High-resolution mass spectrum: Observed value [M + H] ⁺ 314.1603 Calculated value C ₁₄ H ₂₀ NO ₅ S 314.162 IR spectrum (KBr) ν (cm ⁻¹ ): 3359, 1720, 1676,
1527, 1280, 1176, 1064, 755 NMR spectrum (CDCl ₃ ) δ ppm: 7.79 (1H, d, J = 4.3), 7.
77 (1H, d, J = 4.2), 5.37 (1H, t, J = 7.5), 5.09 (1H, dq, J = 7.
3,7.3), 3.93 (3H, s), 1.46 (3H, d, J = 7.6), 1.45 (9H, s).

Example 44 4-[(1R, 2S) -2-benzyloxycarbonyl
Amino-1-hydroxy-3-phenylpropyl] benzo
Methyl perfume (Exemplified Compound No. 6-272)

[0329]

Embedded image (44a) (1R, 2S) -2-benzyloxycarbo
Nylamino-1- (4-bromophenyl) -3-phenyi
4-propane -1-ol Under a nitrogen atmosphere, 4- (N-benzyloxycarbonyl-
L-phenylalanyl) bromobenzene (438 mg,
1 mmol) and reacted in the same manner as in Example 59a,
Purification provided the title compound (413.8 mg, 94%) as a white solid. Melting point: 161.0-162.0 ° C. Specific rotation: [α] ²³ _D = −20.5 (c = 0.29, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 440.0835 calculated value C ₂₃ H ₂₃ NO ₃ Br 440.0862 IR spectrum (KBr) ν (cm ⁻¹ ): 3331, 1696, 1543,
1488, 1454, 1303, 1258, 1007, 823, 751, 698, 491 NMR spectrum (CDCl ₃ ) δ ppm: 7.47 (2H, d, J = 8.2), 7.
41-7.18 (10H, m), 7.07 (2H, d, J = 6.8), 5.05 (1H, d, J = 12.
2), 4.97 (1H, d, J = 12.2), 4.90 (1H, brs), 4.78 (1H, d, J =
8.2), 4.15 (1H, brs), 3.17 (1H, brs), 2.76 (1H, dd, J = 4.
3,14.3), 2.65 (1H, dd, J = 10.0,14.3).

(44b) 4-[(1R, 2S) -2-B
Ndyloxycarbonylamino-1-hydroxy-3-
Phenylpropyl] methyl benzoate (1R, 2S) -2-benzyloxycarbonylamino-1- (4-bromophenyl) -3-phenylpropan-1-ol (220 mg, 0.5 mmol)
The reaction was conducted in the same manner as in Example 58d, and purification was performed to obtain the title compound (210.0 mg, 100%) as a white solid. Melting point: 129.0-131.0 ° C. Specific rotation: [α] ²³ _D −16.3 (c = 0.24, C
HCl ₃ ) High-resolution mass spectrum: Observed value [M + K] ⁺ 458.1371 Calculated value C ₂₅ H ₂₅ NO ₅ K 458.1369 IR spectrum (KBr) ν (cm ⁻¹ ): 3353, 1699, 1532,
1438, 1284, 1117, 1028, 736, 699 NMR spectrum (CDCl ₃ ) δ ppm: 8.02 (2H, d, J = 8.2), 7.
47 (2H, d, J = 7.9), 7.36-7.17 (8H, m), 7.06 (2H, d, J = 6.9),
5.04 (1H, d, J = 12.5), 5.03 (1H, brs), 4.98 (1H, d, J = 12.
3), 4.84 (1H, d, J = 8.3), 4.19 (1H, brs), 3.92 (3H, s), 3.
29 (1H, brs), 2.75 (1H, dd, J = 4.3,14.4), 2.67 (1H, dd, J = 1
0.3,14.0).

Example 45 3- (Nt-butoxycarbonyl-DL-alanyl)
Methyl-2-methoxy-5-methylbenzoate (Exemplified Compound No. 2-119)

[0332]

Embedded image (45a) 3- (Nt-butoxycarbonyl- LA)
Ranyl) -2-methoxy-5-methylbromobenzene 2,6-dibromo-4-methylanisole (9.24
g, 33 mmol) and N ′-(t-butoxycarbonyl) -L-alanine N-methoxy-N-methylamide (2.32 g, 10 mmol), and the reaction was carried out in the same manner as in Example 1b. Compound (2.93 g,
79%) as a white solid. Melting point: 90.0-91.0 ° C. Specific rotation: [α] ²³ _D = 5.2 (c = 1.13, CHC
l ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 372.0787 calculated value C ₁₆ H ₂₃ NO ₄ Br 372.0810 IR spectrum (KBr) ν (cm ⁻¹ ): 3347, 1709, 1688,
1534, 1468, 1367, 1319, 1252, 1174, 1058, 994, 858 NMR spectrum (CDCl ₃ ) δ ppm: 7.53 (1H, s), 7.31 (1H,
s) 5.34 (1H, d, J = 7.1), 5.07 (1H, dq, J = 7.3,7.3), 3.87 (3
H, s), 2.32 (3H, s), 1.44 (9H, s), 1.30 (3H, d, J = 7.1).

(45b) 3- (Nt-butoxycarbo )
Nyl-DL-alanyl) -2-methoxy-5-methyl ammonium
Methyl benzoate 3- (Nt-butoxycarbonyl-L-alanyl)-
2-methoxy-5-methylbromobenzene (186 m
g, 0.5 mmol) and purified in the same manner as in Example 1c, followed by purification to give the title compound (31.2 mg, 18%).
Was obtained as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 352.157 calculated value C ₁₈ H ₂₆ NO ₆ 352.1761 IR spectrum (film) ν (cm ⁻¹ ): 3382, 2979, 1716,
1501, 1475, 1314, 1244, 1208, 1171, 1003, 575 NMR spectrum (CDCl ₃ ) δ ppm: 7.76 (1H, s), 7.50 (1H,
s), 5.37 (1H, d, J = 7.5), 5.06 (1H, dq, J = 7.3, 7.3), 3.94 (3
H, s), 3.87 (3H, s), 2.36 (3H, s), 1.42 (9H, s), 1.32 (3H,
d, J = 7.2).

Example 46 2- (Nt-butoxycarbonyl-L-alanyl) ammonium
2-bromoethyl benzoate (Exemplary Compound No. 1-66)

[0335]

Embedded image (46a) 2- [2- ( N- t-butoxycarbonyl-
L-alanyl) phenyl]-[1,3] dioxolane Under a nitrogen atmosphere, 2- (2-bromophenyl)-[1,3]
Dioxolane (7.56 g, 33 mmol) in tetrahydrofuran (100
n-butyllithium (23.4 ml) at −78 ° C.
ml, 36 mmol). Immediately after dropping, N'-
(T-butoxycarbonyl) -L-alanine N-methoxy-N-methylamide (2.32 g, 10 mmol)
Of tetrahydrofuran (60 ml) was added, and the mixture was further stirred at -78 ° C for 5 minutes. After the completion of the reaction, the reaction was terminated by adding saturated aqueous ammonium chloride (50 ml), diluted with ethyl acetate (100 ml), and the organic layer was separated and dried over anhydrous sodium sulfate. The concentrated residue was purified by silica gel column chromatography (eluent: 9% ethyl acetate / hexane) to give the title compound (2.83 g, 88%) as an oil. Specific rotation: [α] ²³ _D = 16.6 (c = 1.10, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 322.1639 calculated value C ₁₇ H ₂₄ NO ₅ 322.654 IR spectrum (film) ν (cm ⁻¹ ): 3358, 2979, 1699,
1503, 1368, 1249, 1168, 1084, 972, 862, 759 NMR spectrum (CDCl ₃ ) δ ppm: 7.69 (1H, d, J = 7.3), 7.
57 (1H, d, J = 7.6), 7.50 (1H, t, J = 7.5), 7.43 (1H, t, J = 7.
3), 6.20 (1H, s), 5.43 (1H, d, J = 7.4), 5.03 (1H, dq, J = 7.
4,7.4), 4.06-3.95 (4H, m), 1.42 (9H, s), 1.32 (3H, d, J =
7.2).

(46b) 2- (Nt-butoxycarbo )
2-bromoethyl 2- [2- (Nt-butoxycarbonyl-L-alanyl) phenyl]-[1,3] dioxolanyl (n- L-alanyl) benzoate (643 m
g, 2 mmol) in carbon tetrachloride (10 ml) solution.
Brosuccinimide (392 mg, 2.2 mmol) and a small amount of benzoyl peroxide were added, and the mixture was reacted under heating and reflux for 2 hours. After completion of the reaction, the reaction solution was diluted with ethyl acetate (30 ml), and a 10% aqueous sodium thiosulfate solution (10%) was added.
ml), and the organic layer was separated and dried over anhydrous sodium sulfate. The concentrated residue is subjected to silica gel column chromatography (elution solvent: 9% ethyl acetate / hexane to 17%
Purify with ethyl acetate / hexane) to give the title compound (67
7.0 mg, 85%) as an oil. Specific rotation: [α] ²³ _D = −50.0 (c = 0.89, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 400.0737 calculated value C ₁₇ H ₂₃ NO ₅ Br 400.0759 IR spectrum (film) ν (cm ⁻¹ ): 3387, 2979, 1715,
1501, 1449, 1368, 1266, 1166, 1094, 1061, 974, 86
1, 773, 721, 574 NMR spectrum (CDCl ₃ ) δ ppm: 7.96 (1H, d, J = 7.7), 7.
61 (1H, t, J = 7.3), 7.54 (1H, t, J = 7.3), 7.48 (1H, d, J = 7.
5), 5.35 (1H, d, J = 7.9), 4.88 (1H, dq, J = 7.3,7.3), 4.60
(2H, t, J = 6.2), 3.61 (2H, t, J = 6.2), 1.41 (3H, d, J = 7.3),
1.38 (9H, s).

Example 47 2- (Nt-butoxycarbonyl-DL-alanyl)
Benzoic acid hemiacetal (Exemplary Compound No. 7-24)

[0338]

Embedded image 2-bromoethyl 2- (Nt-butoxycarbonyl-L-alanyl) benzoate (200 mg, 0.5 mmol
To a solution of l) in tetrahydrofuran (1 ml) was added a 1 M aqueous sodium hydroxide solution (1 ml). After completion of the reaction, saturated ammonium chloride (5 ml) was added, followed by extraction with ethyl acetate (10 ml) three times, and the organic layer was dried over anhydrous sodium sulfate. The concentrated residue is subjected to silica gel column chromatography (elution solvent: 17% ethyl acetate / hexane to 5%).
(0% ethyl acetate / hexane) to give the title compound (86.9 mg, 59%) as a white solid. High-resolution mass spectrum: measured value [M + H] ⁺ 294.1333 calculated value C ₁₅ H ₂₀ NO ₅ 294.1341 IR spectrum (KBr) ν (cm ⁻¹ ): 3339, 2980, 1771,
1688, 1520, 1369, 1270, 1166, 1055, 910, 770, 69
8.

Example 48 2- (N-benzyloxycarbonyl-L-alanyl)
2-bromoethyl benzoate (Exemplary Compound No. 1-23)
4)

[0340]

Embedded image (48a) 2- [2- (N-benzyloxycarbonyl )
-L-alanyl) phenyl]-[1,3] dioxolane 2- (2-bromophenyl)-[1,3] dioxolane (7.56 g, 33 mmol) and N ′-(benzyloxycarbonyl) -L-alanine N -Methoxy-N-
The reaction was carried out in the same manner as in Example 46a using methylamide (2.66 g, 10 mmol) and purified to obtain the title compound (3.55 g, 100%) as an oil. Specific rotation: [α] ²³ _D = -10.8 (c = 1.28, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 356.1500 calculated value C ₂₀ H ₂₂ NO ₅ 356.1498 IR spectrum (film) ν (cm ⁻¹ ): 3339, 2983, 2892,
1701, 1518, 1454, 1341, 1229, 1084, 972, 756, 699 NMR spectrum (CDCl ₃ ) δ ppm: 7.69 (1H, d, J = 7.5), 7.
54 (1H, d, J = 7.8), 7.51 (1H, t, J = 7.4), 7.43 (1H, t, J = 7.
3), 7.38-7.29 (5H, m), 6.19 (1H, s), 5.74 (1H, d, J = 7.6),
5.14-5.07 (1H, m), 5.11 (2H, s), 4.06-3.94 (4H, m), 1.3
5 (3H, d, J = 7.1).

(48b) 2- (N-benzyloxycal
2-Bromoethyl 2- [2- (N-benzyloxycarbonyl-L-alanyl) phenyl]-[1,3] dioxolane ( bonyl-L-alanyl) benzoate (711 m
g, 2 mmol), and reacted and purified in the same manner as in Example 46b to give the title compound (688.2 mg, 79%).
Was obtained as an oil. Specific rotation: [α] ²³ _D = −36.7 (c = 1.13, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 434.0586 calculated value C ₂₀ H ₂₁ NO ₅ Br 434.0603 IR spectrum (film) ν (cm ⁻¹ ): 3341, 1719, 1509,
1454, 1266, 1092, 1064, 975, 736, 698 NMR spectrum (CDCl ₃ ) δ ppm: 7.96 (1H, d, J = 7.4), 7.
61 (1H, t, J = 7.1), 7.55 (1H, t, J = 7.1), 7.46 (1H, d, J = 7.
4), 7.37-7.30 (5H, m), 5.69 (1H, d, J = 7.9), 5.08 (2H, s),
4.95 (1H, dq, J = 7.4,7.4), 4.58 (2H, t, J = 6.0), 3.58 (2H,
t, J = 6.0), 1.43 (3H, d, J = 7.1).

Example 49 2- (N-benzyloxycarbonyl-DL-arani
Benzoic acid hemiacetal (Exemplary Compound No. 7-6)
8)

[0343]

Embedded image 2- (N-benzyloxycarbonyl-L-alanyl)
2-bromoethyl benzoate (217 mg, 0.5 mm
ol) and purified in the same manner as in Example 47, and purified to give the title compound (97.6 mg, 60%) as an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 328.1158 calculated value C ₁₈ H ₁₈ NO ₅ 328.1185 IR spectrum (film) ν (cm ⁻¹ ): 3332, 1768, 1700,
1529, 1331, 1265, 1055, 908, 757, 697 Example 50 2- (N-benzyloxycarbonyl-L-phenyla
Ranyl) 2-bromoethyl benzoate (Exemplary Compound No. 1-300)

[0344]

Embedded image (50a) 2- [2- (N-benzyloxycarbonyl )
-L-phenylalanyl) phenyl]-[1,3] dio
Xolan 2- (2-bromophenyl)-[1,3] dioxolane (7.56 g, 33 mmol) and N ′-(benzyloxycarbonyl) -L-phenylalanine N-methoxy-N-methylamide (3.42 g, 10 mmol) And purified in the same manner as in Example 46a, to give the title compound (3.67 g, 85%) as an oil. Specific rotation: [α] ²³ _D = 17.3 (c = 0.80, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 432.1805 calculated value C ₂₆ H ₂₆ NO ₅ 432.1811 IR spectrum (film) ν (cm ⁻¹ ): 3338, 2954, 2892,
1701, 1498, 1455, 1347, 1250, 1229, 1083, 942, 75
5, 699 NMR spectrum (CDCl ₃ ) δ ppm: 7.71 (1H, d, J = 7.6), 7.
57 (1H, d, J = 7.4), 7.51 (1H, t, J = 7.4), 7.41 (1H, t, J = 7.
3), 7.35-7.18 (8H, m), 7.10 (2H, d, J = 6.2), 6.08 (1H, s),
5.58 (1H, d, J = 8.4), 5.38 (1H, dt, J = 5.5,8.1), 5.04 (2H,
s), 4.06-3.91 (4H, m), 3.23 (1H, dd, J = 5.3,14.2), 2.87
(1H, dd, J = 7.4,14.2).

(50b) 2- (N-benzyloxycal
Bonyl-L-phenylalanyl) benzoic acid 2-bromo
The same reaction as in Example 46b was carried out using ethyl 2- [2- (N-benzyloxycarbonyl-L-phenylalanyl) phenyl]-[1,3] dioxolane (863 mg, 2 mmol), and the title compound was purified. Compound (763.3m
g, 75%) as a white solid. Melting point: 71.0-73.0 ° C. Specific rotation: [α] ²³ _D = −31.3 (c = 1.17, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 510.0891 calculated value C ₂₆ H ₂₅ NO ₅ Br 510.0917 IR spectrum (KBr) ν (cm ⁻¹ ): 3337, 1697, 1533,
1281, 1140, 1094, 1062, 755, 700 NMR spectrum (CDCl ₃ ) δ ppm: 7.90 (1H, d, J = 6.7), 7.
54-7.50 (2H, m), 7.39 (1H, d, J = 8.7), 7.34-7.15 (10H, m),
5.45 (1H, d, J = 8.9), 5.18 (1H, dt, J = 5.4,8.7), 4.97 (2H,
s), 4.58 (2H, t, J = 6.2), 3.58 (2H, t, J = 6.0), 3.34 (1H, d
d, J = 5.4, 14.3), 2.99 (1H, dd, J = 8.4, 14.3).

Example 51 2- ( N -benzyloxycarbonyl-DL-phenyl)
Alanyl) benzoic acid hemiacetal (Exemplary Compound No. 7-85)

[0347]

Embedded image 2-bromoethyl 2- (N-benzyloxycarbonyl-L-phenylalanyl) benzoate (255 mg,
0.5 mmol) and purified in the same manner as in Example 47, followed by purification to give the title compound (116.3 mg, 58%).
Was obtained as a white solid. High-resolution mass spectrum: measured value [M + H] ⁺ 404.1489 calculated value C ₂₄ H ₂₂ NO ₅ 404.1498 IR spectrum (KBr) ν (cm ⁻¹ ): 3283, 1767, 1691,
1536, 1336, 1263, 1046, 914, 743, 697.

Example 52 2- (O-benzyl-Nt-butoxycarbonyl-L
-Tyrosyl) 2-bromoethyl benzoate (Exemplary Compound No. 1-383)

[0349]

Embedded image (52a) 2- [2- (O-benzyl-Nt-butoxy)
[Cyclocarbonyl-L-tyrosyl) phenyl]-[1,3]
Dioxolane 2- (2-bromophenyl) - [1,3] dioxolane (7.56 g, 33 mmol) and O- benzyl -N '
-(T-butoxycarbonyl) -L-tyrosine N-methoxy-N-methylamide (4.14 g, 10 mmol)
And purified in the same manner as in Example 46a, to give the title compound (3.22 g, 64%) as an oil. Specific rotation: [α] ²³ _D = 12.8 (c = 0.93, CH
Cl ₃ ) High-resolution mass spectrum: measured value [M + K] ⁺ 542.1971 calculated value C ₃₀ H ₃₃ NO ₆ K 542.945 IR spectrum (film) ν (cm ⁻¹ ): 3365, 2977, 1701,
1512, 1367, 1242, 1170, 1084, 1024, 757, 697 NMR spectrum (CDCl ₃ ) δ ppm: 7.71 (1H, d, J = 7.5), 7.
59 (1H, d, J = 7.7), 7.50 (1H, t, J = 7.4), 7.43-7.30 (6H, m),
7.02 (2H, d, J = 8.5), 6.84 (2H, d, J = 8.5), 6.09 (1H, s),
5.31-5.24 (2H, m), 5.02 (2H, s), 4.05-3.93 (4H, m), 3.14
(1H, dd, J = 5.1,14.6), 2.80 (1H, dd, J = 6.8,14.4), 1.37 (9
H, s).

(52b) 2- (O-benzyl-Nt-
2-butoxycarbonyl-L-tyrosyl) benzoic acid
Example 46b using lomoethyl 2- [2- (O-benzyl-N-t-butoxycarbonyl-L-tyrosyl) phenyl]-[1,3] dioxolane (1007 mg, 2 mmol).
And purified to give the title compound (335.9).
mg, 29%) as a white solid. Melting point: 67.0-68.5 ° C. Specific rotation: [α] ²³ _D = −22.9 (c = 0.85, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 582.1473 calculated value C ₃₀ H ₃₃ NO ₆ Br 582.1149 IR spectrum (KBr) ν (cm ⁻¹ ): 3378, 1725, 1692,
1515, 1265, 1168, 1141, 1096, 764, 738, 715, 698 NMR spectrum (CDCl ₃ ) δ ppm: 7.74 (1H, d, J = 8.5), 7.
54-7.48 (2H, m), 7.43-7.30 (6H, m), 7.08 (2H, d, J = 8.6),
6.85 (2H, d, J = 8.5), 5.18 (1H, d, J = 8.9), 5.08 (1H, dt, J =
5.8,8.4), 5.02 (2H, s), 4.59 (2H, t, J = 6.3), 3.60 (2H, t,
J = 6.3), 3.23 (1H, dd, J = 5.5,14.3), 2.92 (1H, dd, J = 7.9,1
4.3), 1.31 (9H, s).

Example 53 2- (O-benzyl-Nt-butoxycarbonyl-L
-Tyrosyl) hemiacetal benzoate (Exemplary Compound No. 7-111)

[0352]

Embedded image 2- (O-benzyl-Nt-butoxycarbonyl-L
-Tyrosyl) 2-bromoethyl benzoate (291 mg,
Using 0.5 mmol), the reaction was carried out in the same manner as in Example 47, followed by purification to obtain the title compound (34.5 mg, 14%) as a white solid. High-resolution mass spectrum: measured value [M + H] ⁺ 476.2601 calculated value C ₂₈ H ₃₀ NO ₆ 476.2074 IR spectrum (KBr) ν (cm ⁻¹ ): 3348, 1769, 1694,
1513, 1244, 1168, 1024, 698.

Example 54 2- (N-benzyloxycarbonyl-O-t-butyl)
-L-seryl) 2-bromoethyl benzoate (Exemplary Compound No. 1-322)

[0354]

Embedded image (54a) 2- [2- (N-benzyloxycarbonyl )
-O-t-butyl-L-seryl) phenyl]-[1,
3] dioxolane 2- (2-bromophenyl)-[1,3] dioxolane (7.56 g, 33 mmol) and N′-benzyloxycarbonyl-Ot-butyl-L-serine N-methoxy-N-methylamide ( (3.38 g, 10 mmol) and reacted in the same manner as in Example 46a, followed by purification to obtain the title compound (3.13 g, 73%) as an oil. Specific rotation: [α] ²³ _D = 34.5 (c = 1.23, CHCl ₃ ) High-resolution mass spectrum: Observed value [M + Na] ⁺ 450.1896 Calculated value C ₂₄ H ₂₉ NO ₆ Na 450.1893 IR spectrum (film) ν (cm ^-1 ): 3434, 3336, 2975, 1705, 1
501, 1342, 1218, 1084, 970, 758, 699 NMR spectrum (CDCl ₃ ) δ ppm: 7.69 (1H, d, J = 7.5), 7.
53 (1H, d, J = 7.7), 7.51 (1H, t, J = 7.5), 7.42 (1H, t, J = 7.
2), 7.37-7.31 (5H, m), 5.95 (1H, s), 5.86 (1H, d, J = 8.3),
5.16 (1H, dt, J = 3.3,8.1), 5.13 (2H, s), 4.15-3.94 (4H,
m), 3.61 (2H, d, J = 3.0), 1.02 (9H, s).

(54b) 2- (N-benzyloxycal )
Bonyl-Ot-butyl-L-seryl) benzoic acid 2-
Bromoethyl 2- [2- (N-benzyloxycarbonyl-Ot-
Example 46b using butyl-L-seryl) phenyl]-[1,3] dioxolane (855 mg, 2 mmol).
And purified to give the title compound (784.9).
mg, 77%) as an oil. Specific rotation: [α] ²³ _D = −3.6 (c = 0.97, CH
Cl ₃ ) High-resolution mass spectrum: actual value [M + H] ⁺ 506.1168 calculated value C ₂₄ H ₂₉ NO ₆ Br 506.1178 IR spectrum (film) ν (cm ⁻¹ ): 3431, 2975, 1723,
1505, 1268, 1089, 963, 774, 699 NMR spectrum (CDCl ₃ ) δ ppm: 8.01 (1H, d, J = 7.3), 7.
60 (1H, t, J = 7.3), 7.53 (1H, t, J = 7.3), 7.48 (1H, d, J = 7.
4), 7.38-7.31 (5H, m), 5.76 (1H, d, J = 8.4), 5.10 (2H, s),
4.99 (1H, dt, J = 3.2,8.4), 4.59 (2H, t, J = 6.3), 3.64 (2H,
dt, J = 3.2, 9.3), 3.58 (2H, d, J = 6.3), 1.09 (9H, s).

Example 55 2- (N-benzyloxycarbonyl-O-t-butyl)
-L- Ceryl) hemiacetal benzoate (Exemplary Compound No. 7-93)

[0357]

Embedded image 2-bromoethyl 2- (N-benzyloxycarbonyl-O-t-butyl-L-seryl) benzoate (253 m
g, 0.5 mmol), and reacted and purified in the same manner as in Example 47 to give the title compound (126.2 mg, 63 mmol).
%) As an oil. High-resolution mass spectrum: measured value [M + H] ⁺ 400.762 Calculated value C ₂₂ H ₂₆ NO ₆ 400.1760 IR spectrum (film) ν (cm ⁻¹ ): 3323, 2976, 1773,
1719, 1515, 1264, 1068, 909, 758, 697.

Embodiment 562- (N-benzyloxycarbonyl-β-t-butyl
-L-aspartyl) 2-bromoethyl benzoate
 (Exemplary Compound No. 1-355)

[0359]

Embedded image (56a) 2- [2- (N-benzyloxycarbonyl )
-Β-t-butyl-L-aspartyl) phenyl]-
[1,3] dioxolane 2- (2-bromophenyl)-[1,3] dioxolane (7.56 g, 33 mmol) and N′-benzyloxycarbonyl-β-t-butyl-L-aspartic acid
N-methoxy-N-methylamide (3.66 g, 10 m
mol)) and purified in the same manner as in Example 46a, and purified to give the title compound (1.78 g, 39%) as an oil. Specific rotation: [α] ²⁷ _D = −28.9 (c = 2.55, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + K] ⁺ 494.1598 calculated value C ₂₅ H ₂₉ NO ₇ K 494.1581 IR spectrum (film) ν (cm ⁻¹ ): 3340, 2979, 1726,
1506, 1369, 1246, 1156, 1085, 945, 757, 699 NMR spectrum (CDCl ₃ ) δ ppm: 7.63 (1H, d, J = 7.7), 7.
53 (1H, d, J = 7.5), 7.48 (1H, t, J = 7.3), 7.40 (1H, t, J = 7.
6), 7.37-7.24 (5H, m), 6.08 (1H, s), 5.82 (1H, d, J = 9.1),
5.30 (1H, dt, J = 5.5,9.2), 5.06 (2H, s), 4.02-3.95 (4H,
m), 2.82 (1H, dd, J = 5.7,16.5), 2.69 (1H, dd, J = 5.8,16.
4), 1.41 (9H, s).

(56b) 2- (N-benzyloxycal
Bonyl-β-t-butyl-L-aspartoyl) benzoate
2-bromoethyl acid 2- [2- (N-benzyloxycarbonyl-β-t-
Butoxy-L-aspartoyl) phenyl]-[1,
3] using dioxolane (911 mg, 2 mmol)
The reaction was conducted in the same manner as in Example 46b, and purification was performed to obtain the title compound (800.3 mg, 75%) as an oil. Specific rotation: [α] ²⁷ _D = 11.8 (c = 0.77, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 534.1132 calculated value C ₂₅ H ₂₉ NO ₇ Br 534.1127 IR spectrum (film) ν (cm ⁻¹ ): 3368, 2978, 1722,
1503, 1368, 1282, 1145, 1093, 1050, 954, 847, 69
9,574 NMR spectrum (CDCl ₃ ) δ ppm: 7.96 (1H, d, J = 7.2), 7.
58 (1H, t, J = 7.2), 7.50 (1H, d, J = 6.5), 7.48 (1H, t, J = 7.
1), 7.33-7.19 (5H, m), 5.78 (1H, d, J = 9.7), 5.23 (1H, dt,
J = 5.2,10.1), 5.01 (1H, d, J = 12.3), 4.96 (1H, d, J = 12.4),
4.59 (2H, t, J = 6.0), 3.60 (2H, d, J = 5.8), 2.94 (1H, dd, J =
5.2,16.8), 2.81 (1H, dd, J = 5.1,16.8), 1.43 (9H, s).

Example 57 2- (N-benzyloxycarbonyl-β-t-butyl)
-L-aspartoyl) benzoic acid hemiacetal (eg
Compound No. 7-102)

[0362]

Embedded image Using 2-bromoethyl 2- (N-benzyloxycarbonyl-β-t-butyl-L-aspartyl) benzoate (267 mg, 0.5 mmol), the reaction was carried out in the same manner as in Example 47, and the mixture was purified to give the title compound ( 71.9m
g, 34%) as an oil. High-resolution mass spectrum: measured value [M + K] ⁺ 466.1255 calculated value C ₂₃ H ₂₅ NO ₇ K 466.1268 IR spectrum (film) ν (cm ⁻¹ ): 3324, 1773, 1728,
1333, 1286, 1257, 1156, 1049, 910, 697 Example 58 3-[(1R, 2S) -2-benzyloxycarbonyl
Amino-1-hydroxypropyl] methyl benzoate (Exemplified Compound No. 5-366)

[0363]

Embedded image (58a) N′-benzyloxycarbonyl-L-ara
Nin N-methoxy-N-methylamide Under a nitrogen atmosphere, a solution of N-benzyloxycarbonyl-L-alanine (13.39 g, 60 mmol) in methylene chloride (200 ml) was added at room temperature to triethylamine (20.
9 ml, 150 mmol), N, O-dimethylhydroxylamine hydrochloride (7.02 g, 72 mmol), 1-
Hydroxybenzotriazole (10.54 g, 78m
mol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (14.98 g, 78 m
mol) was added. After completion of the reaction, water (100 ml) was added, and the organic layer was washed with water (100 ml), a saturated aqueous solution of sodium hydrogencarbonate (100 ml) and a saturated saline solution (100 ml).
1) and dried over anhydrous sodium sulfate. The concentrated residue is purified by recrystallization (methylene chloride and hexane),
The title compound (15.28 g, 96%) was obtained as a white solid. NMR spectrum (CDCl ₃ ) δ ppm: 7.36 to 7.30 (5H, m), 5.5
5 (1H, d, J = 7.3), 5.13 (1H, d, J = 11.7), 5.07 (1H, d, J = 12.
5), 4.76-4.73 (1H, m), 3.78 (3H, s), 3.21 (3H, s), 1.35 (3
H, d, J = 7.3).

(58b) 3- (N-benzyloxycal
Bonyl-L-alanyl) bromobenzene Under a nitrogen atmosphere, 1,3-dibromobenzene (4 ml, 3
N-butyl lithium (23.4 ml, 36 mmol) in a solution of 3 mmol) in tetrahydrofuran (100 ml) at -78 ° C.
mmol). Immediately after the dropwise addition, a solution of N′-benzyloxycarbonyl-L-alanine N-methoxy-N-methylamide (2.66 g, 10 mmol) in tetrahydrofuran (60 ml) was added, and the mixture was further stirred at −78 ° C. for 5 minutes. After completion of the reaction, saturated aqueous ammonium chloride solution (50
ml), and diluted with ethyl acetate (100 ml). The organic layer was separated and dried over anhydrous sodium sulfate. The concentrated residue is subjected to silica gel column chromatography (eluent:
The residue was purified with 5% ethyl acetate / hexane to give the title compound (3.62 g, 100%) as an oil. Specific rotation: [α] ²³ _D = −2.3 (c = 2.46, CH
Cl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 362.0395 calculated value C ₁₇ H ₁₇ NO ₃ Br 362.0392 IR spectrum (film) ν (cm ⁻¹ ): 3331, 1720, 1503,
1454, 1347, 1251, 1218, 1063, 735, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, s), 7.89 (1H,
d, J = 7.8), 7.73 (1H, d, J = 8.2), 7.40-7.30 (6H, m), 5.79
(1H, d, J = 7.1), 5.29 (1H, dq, J = 7.2,7.2), 5.13 (2H, s),
1.43 (3H, d, J = 7.0).

(58c) (1R, 2S) -2-benzyl
Oxycarbonylamino-1- (3-bromophenyl)
Under a nitrogen atmosphere of propan-1-ol , 3- (N-benzyloxycarbonyl-
L-alanyl) bromobenzene (724 mg, 2 mmol
To a solution of 1) in trifluoroacetic acid (2 ml) was added dimethylphenylsilane (0.46 ml, 3 mmol) at 0 ° C., and the mixture was stirred for 5 hours. After completion of the reaction, the reaction was terminated by adding water (5 ml), diluted with ethyl acetate (10 ml),
The organic layer was washed with water (5 ml, twice), a saturated aqueous solution of sodium hydrogen carbonate (5 ml, twice), brine (5 ml, once) and dried over anhydrous sodium sulfate. The concentrated residue is subjected to silica gel column chromatography (elution solvent: 17%
Purify with ethyl acetate / hexane) to give the title compound (71
(4.3 mg, 98%) as a single stereoisomer, a white solid. Melting point: 109.0-110.0 ° C. Specific rotation: [α] ²³ _D = −36.2 (c = 0.57, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 364.0553 calculated value C ₁₇ H ₁₉ NO ₃ Br 364.0548 IR spectrum (KBr) ν (cm ⁻¹ ): 3336, 1686, 1541,
1319, 1265, 1239, 1067, 1028, 734, 699 NMR spectrum (CDCl ₃ ) δ ppm: 7.51 (1H, s), 7.41-7.3
0 (6H, m), 7.25 (1H, d, J = 7.8), 7.19 (1H, t, J = 7.8), 5.12
(2H, s), 4.97 (1H, d, J = 8.0), 4.86 (1H, s), 4.00 (1H, br
s), 3.03 (1H, d, J = 2.8), 0.99 (3H, d, J = 6.9).

(58d) 3-[(1R, 2S) -2-B
Ndyloxycarbonylamino-1-hydroxypropyl
[1] Under a nitrogen atmosphere of methyl benzoate, a solution of (1R, 2S) -2-benzyloxycarbonylamino-1- (3-bromophenyl) propan-1-ol (182 mg, 0.5 mmol) in tetrahydrofuran (15 ml) was added. At 78 ° C., a hexane solution of n-butyllithium (1.0 ml, 1.5 mmol
l), a solution of t-butyllithium in pentane (0.61 m
1, 1.0 mmol) were added sequentially. Immediately after the addition, dry ice (1.0 g) was added, and the mixture was further stirred at -78 ° C for 5 minutes. After completion of the reaction, 1 M hydrochloric acid (5 ml) was added to terminate the reaction, and the reaction mixture was extracted twice with ethyl acetate (10 ml) and dried over anhydrous sodium sulfate. Toluene (3 ml) and methanol (3 ml) were added to the concentrated residue,
A hexane solution of trimethylsilyldiazomethane was added until the reaction solution turned yellow in trimethylsilyldiazomethane. Excess trimethylsilyldiazomethane was decomposed with acetic acid, and the concentrated residue was purified by silica gel column chromatography (eluent: 20% ethyl acetate / hexane) to obtain the title compound (111.2 mg, 65%) as a white solid. Melting point: 99.0-101.0 ° C. Specific rotation: [α] ²³ _D = −39.9 (c = 0.47, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 344.1505 calculated value C ₁₉ H ₂₂ NO ₅ 344.1498 IR spectrum (KBr) ν (cm ⁻¹ ): 3327, 1722, 1687,
1539, 1288, 1231, 1201, 1109, 1034, 753, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.01 (1H, s), 7.95 (1H,
d, J = 7.9), 7.55 (1H, d, J = 7.5), 7.41 (1H, t, J = 7.6), 7.37
-7.31 (5H, m), 5.12 (2H, s), 4.99 (1H, d, J = 8.2), 4.96 (1
H, s), 4.08-4.06 (1H, m), 3.90 (3H, s), 3.07 (1H, brs),
0.99 (3H, d, J = 6.9).

Example 59 3-[(1R, 2S) -2-benzyloxycarbonyl
Amino-1-hydroxy-3-phenylpropyl] benzo
Methyl perfume (Exemplified Compound No. 5-467)

[0368]

Embedded image (59a) (1R, 2S) -2-benzyloxycarbo
Nylamino-1- (3-bromophenyl) -3-phenyi
3-propane -1-ol under a nitrogen atmosphere, 3- (N-benzyloxycarbonyl-
L-phenylalanyl) bromobenzene (877 mg,
2mmol) in toluene (10 ml) at -78 ° C in toluene solution of diisobutylaluminum hydride (6.
0 ml, 6 mmol) and stirred for 30 minutes. After the completion of the reaction, a 10% aqueous solution of potassium sodium tartrate (10 m
l) was added to terminate the reaction, and the mixture was vigorously stirred at room temperature for 1 hour. The reaction solution was extracted three times with ethyl acetate (10 ml),
Dry over anhydrous sodium sulfate. The concentrated residue was purified by silica gel column chromatography (eluent: 25% ethyl acetate / hexane) to give the title compound (854.8m).
g, 97%) as a white solid. Melting point: 137.0-141.0 ° C. Specific rotation: [α] ²³ _D = −30.4 (c = 0.42, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 440.0862 calculated value C ₂₃ H ₂₃ NO ₃ Br 440.0861 IR spectrum (KBr) ν (cm ⁻¹ ): 3335, 1689, 1543,
1258, 1017, 749, 696 NMR spectrum (CDCl ₃ ) δ ppm:
7.57 (1H, s), 7.42 (1H, d, J = 7.9), 7.38-7.17 (10H, m), 7.
08 (2H, d, J = 6.8), 5.05 (1H, d, J = 12.1), 4.98 (1H, d, J = 12.
3), 4.94 (1H, brs), 4.83 (1H, d, J = 7.9), 4.16 (1H, brs),
3.19 (1H, brs), 2.77 (1H, dd, J = 4.3,14.4), 2.67 (1H, dd, J
= 10.2, 14.3).

(59b) 3-[(1R, 2S) -2-B
Ndyloxycarbonylamino-1-hydroxy-3-
[Phenylpropyl] methyl benzoate (1R, 2S) -2-benzyloxycarbonylamino-1- (3-bromophenyl) -3-phenylpropan-1-ol (220 mg, 0.5 mmol)
The reaction was carried out and purified in the same manner as in Example 58b to give the title compound (210.0 mg, 100%) as a white solid. Melting point: 137.0-140.0 ° C. Specific rotation: [α] ²³ _D = −32.8 (c = 0.36, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 420.820 calculated value C ₂₅ H ₂₆ NO ₅ 420.1811 IR spectrum (KBr) ν (cm ⁻¹ ): 3332, 1725, 1690,
1541, 1290, 1200, 1107, 1022, 750, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.07 (1H, s), 7.97 (1H,
d, J = 7.6), 7.61 (1H, d, J = 8.0), 7.43 (1H, t, J = 7.7), 7.37
-7.16 (8H, m), 7.07 (2H, d, J = 6.5), 5.10-4.94 (3H, m), 4.
87 (1H, d, J = 8.4), 4.20-4.14 (1H, m), 3.91 (3H, s), 3.29
(1H, brs), 2.77 (1H, dd, J = 4.4,14.4), 2.69 (1H, dd, J = 9.
9,14.3).

Example 60 3-[(1R, 2S) -2-benzyloxycarbonyl
Amino-1-hydroxy-3-methylbutyl] benzoic acid
Methyl (exemplified compound number 5-414)

[0371]

Embedded image (60a) (1R, 2S) -2-benzyloxycarbo
Nylamino-1- (3-bromophenyl) -3-methyl
The same reaction as in Example 59a was carried out using butan-1-ol 3- (N-benzyloxycarbonyl-L-valyl) bromobenzene (781 mg, 2 mmol), and the title compound (78) was purified.
(5.0 mg, 100%) as a white solid. Melting point: 97.5-98.0 ° C. Specific rotation: [α] ²³ _D = −64.6 (c = 1.06, CHCl ₃ ) High-resolution mass spectrum: Observed value [M + H] ⁺ 392.0880 Calculated value C ₁₉ H ₂₃ NO ₃ Br 392.0862 IR spectrum (KBr) ν (cm ⁻¹ ): 3322, 1689, 1541, 1301, 12
55, 1045, 1006, 783, 743, 696, 673 NMR spectrum (CDCl ₃ ) δ ppm: 7.50 (1H, s), 7.41-7.2
6 (7H, m), 7.18 (1H, t, J = 7.9), 5.11 (1H, d, J = 12.2), 5.02
(1H, d, J = 12.3), 4.83 (1H, t, J = 4.6), 4.65 (1H, d, J = 9.8),
3.83 (1H, dt, J = 5.0,10.6), 2.87 (1H, d, J = 4.2), 1.76 (1
H, dqq, J = 6.6,6.6,6.6), 1.01 (3H, d, J = 6.7), 0.89 (3H, d,
J = 6.8).

(60b) 3-[(1R, 2S) -2-B
Ndyloxycarbonylamino-1-hydroxy-3-
Methylbutyl ] methyl benzoate (1R, 2S) -2-benzyloxycarbonylamino-1- (3-bromophenyl) -3-methylbutane-1
-All (196 mg, 0.5 mmol) was reacted in the same manner as in Example 58d, purified, and purified using the title compound (1
37.1 mg, 74%) as a white solid. Melting point: 130.0-131.0 ° C. Specific rotation: [α] ²³ _D = −66.3 (c = 0.40, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 372.833 calculated value C ₂₁ H ₂₆ NO ₅ 372.1811 IR spectrum (KBr) ν (cm ⁻¹ ): 3468, 3328, 2960,
1721, 1702, 1546, 1453, 1435, 1295, 1249, 1209, 10
98, 1040, 1000, 757, 697 NMR spectrum (CDCl ₃ ) δp
pm: 8.00 (1H, s), 7.95 (1H, d, J = 7.6), 7.57 (1H, d, J = 7.
8), 7.39 (1H, t, J = 7.8), 7.36-7.25 (5H, m), 5.07 (1H, d, J
= 12.2), 4.99 (1H, d, J = 12.2), 4.90 (1H, t, J = 4.7), 4.67
(1H, d, J = 9.9), 3.89 (3H, s), 3.88-3.85 (1H, m), 2.88 (1H,
d, J = 4.0), 1.84-1.75 (1H, m), 1.01 (3H, d, J = 6.7), 0.90
(3H, d, J = 6.8).

Example 61 3-[(1R, 2S) -2-t-butoxycarbonyla
Mino-1-hydroxy-4-methylpentyl] benzoic acid
Methyl (Exemplified Compound No. 5-172)

[0374]

Embedded image (61a) (1R, 2S) -2-t-butoxycarboni
Rumin-1- (3-bromophenyl) -4-methylpe
The reaction was carried out in the same manner as in Example 59a using tan- 1-ol 3- (Nt-butoxycarbonyl-L-leucyl) bromobenzene (741 mg, 2 mmol), and the title compound (745.0 mg, 100
%) As a white solid. Melting point: 103.0-104.0 ° C. Specific rotation: [α] ²³ _D = −75.3 (c = 0.53, C
HCl ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 372.1198 calculated value C ₁₇ H ₂₇ NO ₃ Br 372.1174 IR spectrum (KBr) ν (cm ⁻¹ ): 3381, 2958, 1688,
1522, 1450, 1367, 1297, 1253, 1169, 1050, 999, 78
8,701 NMR spectrum (CDCl ₃ ) δ ppm: 7.50 (1H, s), 7.40 (1H,
d, J = 6.5), 7.23-7.18 (2H, m), 4.78 (1H, s), 4.42 (1H, d, J
= 7.8), 4.01-3.96 (1H, m), 3.88 (1H, d, J = 4.6), 1.67-1.5
7 (1H, m), 1.47 (9H, s), 1.15 (2H, t, J = 6.7), 0.88 (3H, d, J
= 6.6), 0.85 (3H, d, J = 6.6).

(61b) 3-[(1R, 2S) -2-t
-Butoxycarbonylamino-1-hydroxy-4-me
Tylpentyl] methyl benzoate (1R, 2S) -2-t-butoxycarbonylamino-
1- (3-bromophenyl) -4-methylpentane-1
Using ol (186 mg, 0.5 mmol), the reaction was carried out in the same manner as in Example 58d, purified, and the title compound (1
10.4 mg, 63%) as a white solid. Melting point: 116.0-118.0 ° C. Specific rotation: [α] ²³ _D = −69.2 (c = 0.28, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 352.2151 calculated value C ₁₉ H ₃₀ NO ₅ 352.2124 IR spectrum (KBr) ν (cm ⁻¹ ): 3489, 3344, 2926,
1706, 1679, 1531, 1303, 1172, 756 NMR spectrum (CDCl ₃ ) δ ppm: 8.00 (1H, s), 7.96 (1H,
d, J = 7.9), 7.53 (1H, d, J = 7.7), 7.42 (1H, t, J = 7.7), 4.88
(1H, s), 4.43 (1H, d, J = 8.0), 4.04-4.00 (1H, m), 3.92 (3
H, s), 3.87 (1H, d, J = 4.4), 1.70-1.59 (1H, m), 1.47 (9H,
s), 1.15 (2H, t, J = 7.2), 0.87 (3H, d, J = 6.6), 0.84 (3H, d,
J = 6.5).

Example 62 3-[(1R, 2S) -2-benzyloxycarbonyl
Amino-3-t-butoxy-1-hydroxypropyl]
Methyl benzoate (Exemplary Compound No. 5-506)

[0377]

Embedded image (62a) (1R, 2S) -2-benzyloxycarbo
Nylamino-1- (3-bromophenyl) -3-t-bu
Toxipropan-1-ol 3- (N-benzyloxycarbonyl-O-t-butyl-L-seryl) bromobenzene (869 mg, 2 mmol)
l) was reacted and purified in the same manner as in Example 59a,
The title compound (744.4 mg, 85%) was obtained as an oil. Specific rotation: [α] ²³ _D = 7.1 (c = 1.31, CHC
l ₃ ) High-resolution mass spectrum: measured value [M + H] ⁺ 436.1125 calculated value C ₂₁ H ₂₇ NO ₄ Br 436.1123 IR spectrum (film) ν (cm ⁻¹ ): 3439, 2975, 1716,
1509, 1237, 1194, 1069, 777, 738, 698 NMR spectrum (CDCl ₃ ) δ ppm: 7.58 (1H, s), 7.41-7.3
0 (7H, m), 7.23 (1H, t, J = 7.8), 5.74 (1H, d, J = 8.7), 5.14
(2H, s), 4.95 (1H, dd, J = 3.3,8.8), 4.36 (1H, d, J = 9.0),
3.97-3.95 (1H, m), 3.44 (1H, dd, J = 2.5,9.3), 3.39 (1H, d
d, J = 2.2,9.1), 1.14 (9H, s).

(62b) 3-[(1R, 2S) -2-B
Ndyloxycarbonylamino-3-t-butoxy-1
-Hydroxypropyl] methyl benzoate (1R, 2S) -2-benzyloxycarbonylamino-1- (3-bromophenyl) -3-t-butoxypropan-1-ol (218 mg, 0.5 mmol) The reaction was carried out in the same manner as in Example 58d, and purification was carried out to give the title compound (155.8 mg, 75%) as an oil. Specific rotation: [α] ²³ _D = 6.2 (c = 1.11, CHC
l ₃ ) High-resolution mass spectrum: measured value [M + Na] ⁺ 438.1888 calculated value C ₂₃ H ₂₉ NO ₆ Na 438.1892 IR spectrum (film) ν (cm ⁻¹ ): 3443, 2975, 1724,
1509, 1289, 1199, 1075, 754, 699 NMR spectrum (CDCl ₃ ) δ ppm: 8.09 (1H, s), 7.96 (1H,
d, J = 7.7), 7.60 (1H, d, J = 7.6), 7.44 (1H, t, J = 7.7), 7.38
-7.32 (5H, m), 5.77 (1H, d, J = 8.8), 5.14 (2H, s), 5.02 (1
H, brs), 4.40 (1H, d, J = 8.4), 4.02-3.99 (1H, m), 3.92 (3
H, s), 3.44 (1H, dd, J = 2.2,9.4), 3.38 (1H, dd, J = 2.0,9.
4), 1.14 (9H, s).

Example 63 3-[(1R, 2S) -2-benzyloxycarbonyl
Amino-1-hydroxy-3- (N-methoxycarboni
Ruin-3-yl) propyl] methyl benzoate (Exemplified Compound No. 5-489)

[0380]

Embedded image (63a) (1R, 2S) -2-benzyloxycarbo
Nylamino-1- (3-bromophenyl) -3- (in
Do-3-yl) propan-1-ol 3- (N-benzyloxycarbonyl-L-tryptophyl) bromobenzene (955 mg, 2 mmol) was reacted in the same manner as in Example 59a, purified, and purified to give the title compound ( 693.2 mg, 72%) as a white solid. Melting point: 127.0-130.0 ° C. Specific rotation: [α] ²³ _D = −35.2 (c = 0.39, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 479.0979 calculated value C ₂₅ H ₂₄ N ₂ O ₃ Br 479.0971 IR spectrum (KBr) ν (cm ⁻¹ ): 3412, 1690, 1517,
1456, 1341, 1265, 1046, 744, 698 NMR spectrum (CDCl ₃ ) δ ppm: 7.97 (1H, s), 7.57 (1H,
s), 7.42 (2H, d, J = 6.8), 7.36-7.15 (9H, m), 7.07 (1H, t, J =
7.4), 6.92 (1H, s), 5.06 (1H, d, J = 12.0), 4.98-4.94 (2H,
m), 4.86 (1H, d, J = 7.6), 4.27 (1H, brs), 3.33 (1H, brs),
2.89 (2H, d, J = 6.8).

(63b) 3-[(1R, 2S) -2-B
Ndyloxycarbonylamino-1-hydroxy-3-
(N-methoxycarbonylindo-3-yl) propyl
M] methyl benzoate (1R, 2S) -2-benzyloxycarbonylamino-1- (3-bromophenyl) -3- (indo-3-yl) propan-1-ol (240 mg, 0.5 mmol)
Using l), the reaction was conducted in the same manner as in Example 58d, and purification was performed to obtain the title compound (206.3 mg, 80%) as a white solid. Melting point: 68.0-70.0 ° C. Specific rotation: [α] ²³ _D = −24.1 (c = 0.27, C
HCl ₃ ) High-resolution mass spectrum: observed value [M + H] ⁺ 517.1980 calculated value C ₂₉ H ₂₉ N ₂ O ₇ 517.1975 IR spectrum (KBr) ν (cm ⁻¹ ): 3354, 2954, 1724,
1532, 1456, 1382, 1289, 1262, 1092, 750, 698 NMR spectrum (CDCl ₃ ) δ ppm: 8.12 (1H, d, J = 7.2), 8.
09 (1H, s), 7.97 (1H, d, J = 6.7), 7.63 (1H, d, J = 7.2), 7.42
(1H, t, J = 7.8), 7.39-7.15 (9H, m), 5.07-4.98 (4H, m), 4.
32-4.26 (1H, m), 3.98 (3H, s), 3.90 (3H, s), 3.24 (1H, br
s), 2.91-2.81 (2H, m).

[0382]

The compounds having the general formulas (I) and (II) of the present invention are useful as templates for the synthesis of peptide mimetics.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 213/50 C07D 213/50 295/18 295/18 333/40 333/40 333/40 F-term (Reference) 4C023 HA02 4C055 AA01 BA03 BA27 BA57 BA58 CA01 DA01 4C069 AA02 4C204 BB01 CB03 DB16 EB01 FB01 GB01 4H006 AA01 AB80 RA06 RA54 TA04

Claims (11)

[Claims] 1. A compound represented by the following general formula (I) or a base addition salt or an acid addition salt: [In the formula, Ar represents an aryl group or a heteroaryl group, and R ¹ and R ² are the same or different and each represents a hydrogen atom, a lower alkyl group, an aryl group, or a group selected from a substituent group a. R ³ represents a hydrogen atom, a lower alkyl group, a heteroaryl group, an aralkyl group, a heteroaryl lower alkyl group, or a substituent group a. Represents a lower alkyl group, a heteroaryl group, an aralkyl group or a heteroaryl lower alkyl group substituted by 1 to 3 groups, or a nitrogen atom adjacent to the carbon atom to which R ³ is bonded and R ³ May together form a ring, and R ⁴ represents an amine residue or a group having the formula —O—R ⁷ (where R ⁷ represents a hydrogen atom or an ester residue). But, However, when R ³ is a methyl group, R ⁴ is not a methoxy group, and when R ³ is a parahydroxybenzyl group, R ⁴ is not a hydroxy group, and R ⁵ is a hydrogen atom, a lower alkyl group. , An aryl group, an aralkyl group, a group selected from substituent group a, or a lower alkyl group, an aryl group or an aralkyl group substituted by 1 to 3 groups selected from substituent group a, When n represents an integer of 2 or more, R ⁵ represents the same or different groups, and when the dashed line represents a single bond, R ⁶ is a hydroxy group; R ⁶ to represent a double bond is an oxygen atom, a substituent group a is a hydroxy group, a lower alkoxy group, an aryloxy group, an aralkyloxy group, a mercapto group, a lower alkylthio group, an arylthio group, aralkylthio , Formyl group, lower alkylcarbonyl group, arylcarbonyl group, aralkylcarbonyl group, carboxy group, lower alkoxycarbonyl group, aryloxycarbonyl group, aralkyloxycarbonyl group, (lower alkyl, aryl, aralkyl, carboxy, lower alkoxycarbonyl, aryl An amino group, which may be mono- or di-substituted with a group selected from the group consisting of oxycarbonyl and aralkyloxycarbonyl, and a mono- or di-substituted group with a group selected from the group consisting of lower alkyl, aryl and aralkyl May be)
It consists of a carbamoyl group, an amidino group, a guanidino group, a cyano group, a halogen atom, a nitro group, a sulfo group, and a halogenoalkyl group. ]. 2. The compound according to claim 1, wherein the dashed line represents a double bond, and R ⁶ is an oxygen atom, or a base addition metal salt or acid addition salt thereof. 3. The compound according to claim 1, wherein the dashed line represents a single bond, and R ⁶ is a hydroxy group, or a base addition salt or an acid addition salt thereof. 4. The compound according to any one of claims 1 to 3, wherein Ar is benzene, pyridine, quinoline or thiophene, or a base addition salt or an acid addition salt thereof. 5. The compound according to any one of claims 1 to 4, wherein R ¹ is a hydrogen atom, or a base addition salt or an acid addition salt thereof. 6. The compound according to any one of claims 1 to 5, wherein R ² is a protecting group for an amino group, or a base addition salt or an acid addition salt thereof. 7. A lower alkyl, aralkyl or heteroaryl lower alkyl, wherein R ³ is substituted with 1 to 3 hydrogen atoms, lower alkyl, aralkyl, heteroaryl lower alkyl, or a group selected from substituent group a. The compound according to any one of claims 1 to 6, wherein the group or a nitrogen atom adjacent to the carbon atom to which R ³ is bonded and R ³ form a pyrrolidine ring or a piperidine ring, or a compound thereof. Base addition salts or acid addition salts. 8. A compound according to claim 1, wherein R ³ is a hydrogen atom, methyl, ethyl, propyl, isopropyl, isobutyl, benzyl, 2-methylthioethyl, 4- (benzyloxycarbonylamino) butyl, 4-benzyloxybenzyl, t-butoxycarbonylmethyl , 1- (t-butoxycarbonyl)
An ethyl, 2- (t-butoxycarbonyl) ethyl or 3-indolylmethyl group, or a nitrogen atom adjacent to the carbon atom to which R ³ is bonded and R ³ form a pyrrolidine ring or a piperidine ring The compound according to any one of claims 1 to 6, or a base addition salt or an acid addition salt thereof. 9. The compound according to any one of claims 1 to 6, wherein the configuration at the skeleton carbon to which R ³ is bonded is a configuration derived from a natural amino acid, or a base addition salt or acid thereof. Addition salt. 10. The compound according to any one of claims 1 to 9, wherein n is 1, or a base addition salt or an acid addition salt thereof. 11. The method according to claim 1, wherein R ⁵ is a hydrogen atom.
The compound according to any one of the above, or a base addition salt or an acid addition salt thereof.