WO1998022451A1 - Taxol derivatives - Google Patents

Abstract

Substituted taxol derivatives of general formula (I) having an antitumor activity, wherein R6 is optionally substituted alkyl, alkenyl or alkynyl; and R5 is methyl, or together with R4 forms a three-membered ring, provided the cases wherein R3 is hydrogen, R4 is hydrogen or hydroxyl, and the linkage between the carbon atoms to which R?3 and R4¿ are bonded respectively is a single bond are excepted.

Description

 Specification

 Taxol derivatives Technical field

 The present invention relates to a novel taxol derivative having an antitumor effect. Background art

 Evening sol is a natural product represented by the following chemical structural formula, and is obtained in small amounts from the stem of the yew tree.

Taxol is known to have antitumor activity, and its mechanism of action is based on the inhibitory effect of microtubule depolymerization on cell division. Its clinical application is expected as an agent.

Until now, taxol was only available in trace amounts from nature. In recent years, a taxol precursor that can be obtained in relatively large quantities from yew leaves, etc. is 10-0-0-deacetylbaccatin.

A taxol derivative semi-synthesized by using as a raw material has been reported (see Japanese Patent Application Laid-Open No. H03-505725). Among them, a compound having the following structure (Taxotere) has attracted attention as a compound having an antitumor activity equal to or higher than that of Taxol, and is currently being developed as an antitumor agent.

Thus, the derivatives represented by taxol and evening xotere are promising antitumor agents. However, clinical trials have shown that its efficacy against gastrointestinal cancers, especially colon cancer, is low, and derivatives having stronger antitumor effects are desired. Disclosure of the invention Conventionally, as the substituent at the 10-position of a taxol derivative, an acetoxyl group, a hydroxyl group, and the hydroxyl group further substituted with an acyl group, an alkylaminocarbonyl group (EP 524,093) and the like have been reported. Derivatives in which the 10-position has been replaced by a hydrogen atom (Tetrahedron Lett., 34, 4921 (1993)) are also known. As a result of intensive studies, the present inventors have found that a derivative in which an alkyl group or an alkyl group having a substituent is introduced at the 10-position has strong antitumor activity, and completed the present invention.

 The present invention provides a compound represented by the general formula (I):

[Where,

 R ′ represents a phenyl group, and the phenyl group may have, as a substituent, one or more groups selected from the group consisting of a halogen atom, an alkyl group and an alkoxyl group.

R ² represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an alkoxyl group; these alkyl group, alkenyl group, alkynyl group, cycloalkyl group and alkoxyl group are a nitrogen atom, a hydroxyl group, a carboxyl group, , An alkoxyl group, an aryloxy group, a phenyl group, an amino group, an alkylamino group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group as one substituent. Alternatively, it may have a plurality. R ³ represents an amino group, a hydrogen atom, a hydroxyl group, a halogen atom, an alkoxyl group, an azido group or an acyloxy group having one or two substituents selected from the group consisting of an alkyl group and an acyl group.

R ⁴ represents an amino group, a hydrogen atom, a hydroxyl group, a halogen atom, an alkoxyl group, an azide group or an acyloxy group having one or two substituents selected from the group consisting of an alkyl group and an acyl group; Groups and alkoxy groups include halogen atom, hydroxyl group, carboxyl group, cycloalkyl group, alkoxy group, aryl group, aryloxy group, amino group, alkylamino group, alkoxycarbonyl group, aryloxycarbonyl group, and acyl group. Substituted with a group selected from the group consisting of a group, an aramino group, an acyloxy group and a heterocyclic group (the heterocyclic group may have one or more alkyl groups on the atoms constituting the ring). It may have one or more groups.

Also, R ³ and R ⁴ are united to give the formula

(In the formula, Q represents an oxygen atom, N—R ⁷ or CR ⁸ R ⁹ , and R ⁷ , R ⁸ and R ′ each independently represent an alkyl group or an acyl group.)

May be formed.

R ⁵ represents a methyl group,

Or may become connexion such together with R ^4, R ⁴ and each R ⁵ is taken together form 3-membered ring with the carbon atom bonded structure.

R ⁶ represents an alkyl group, an alkenyl group or an alkynyl group,

These alkyl group, alkenyl group and alkynyl group include carboxyl group, alkoxyl group, aryloxy group, alkoxycarbonyl group, aryloxy group, cyano group, hydroxyl group, amino group, alkylamino group, acyl group, and acylamino group. Group, acyloxy group, alkoxycarbonylamino group, alkylthio group, alkylsulfinyl group, alkylsulfonyl group and formula One NX

(X represents an oxygen atom, a sulfur atom, CH ₂ , CH—Y, Ν Η or Ν— 、, and Υ represents an alkyl group.) The size of a 3- to 8-membered ring represented by Or a saturated or unsaturated heterocyclic group containing a nitrogen atom of the formula (the heterocyclic group may have one or more alkyl groups on a carbon atom constituting the ring). And may have one or more substituents selected from

Ζ ¹ represents a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group,

Zeta ² is a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group,

Zeta ³ is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group means a Ari Le group or a heterocyclic group, the alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, Ariru group and heterocyclic group, halogen Atom, hydroxyl, carboxyl, alkyl, alkoxyl, phenyl, amino, alkylamino, aminoalkyl, alkylaminoalkyl, alkoxycarbonyl, aryloxycarbonyl, acyl, unamino and It may have one or more substituents selected from the group consisting of acyloxy groups.

Zeta ⁴ denotes an alkyl group, Ariru group or an alkoxyl group, these alkyl group, Ariru group and alkoxyl group, a halogen atom, a hydroxyl group, carboxyl group, an alkyl group, an alkoxyl group, Fuweniru group, an amino group, an alkylamino Group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group, and an acyloxy group. Is also good.

 In addition,

R ⁴

.R ³ The dotted line of the portion means that the bond of the portion may be a double bond. -] (Where R ³ is a hydrogen atom, R ⁴ is a hydrogen atom or a hydroxyl group, and the bond between the carbon atom bonded to R ³ and the carbon atom bonded to R ⁴ is a single bond ) And its salts.

 Next, terms used in this specification will be described.

“C, to C ₆ ” means having 1 to 6 carbon atoms, for example, “C _{2 to} C ₆ alkenyl group” means an alkenyl group having 2 to 6 carbon atoms.

 The “alkyl group”, “alkenyl group” and “alkynyl group” may be linear or branched, and preferably have 1 to 6 carbon atoms (in the case of alkenyl and alkynyl groups) from 6 carbon atoms.

 "Alkoxyl group" means a group in which an alkyl group is bonded to a group 10-, and the alkyl group may be substituted by a phenyl group (which may have a substituent). Examples include benzyloxy, phenethyloxy, p-methoxybenzyloxy and the like. The alkyl moiety preferably has 1 to 6 carbon atoms.

 The “alkoxycarbonyl group” means a group in which an alkyl group is bonded to a C 100 —oxygen atom, and the alkyl group is a phenyl group (which may have a substituent). It may be substituted, and such examples include benzyloxycarbonyl, phenethyloquincarbonyl, p-methoxybenzyloxycarbonyl and the like. The alkyl moiety preferably has 1 to 6 carbon atoms.

 The "aryl group" means a monovalent group obtained by removing one hydrogen atom from the nucleus of an aromatic hydrocarbon, and examples thereof include phenyl, trityl, biphenyl, and naphthyl.

 The bonding position of the amino group of the "aminoalkyl group" may be any position of the alkyl group. The alkyl group preferably has 1 to 6 carbon atoms.

 "Alkylamino group" refers to an amino group substituted with one alkyl group or an amino group substituted with two alkyl groups (the two alkyl groups may be the same or different). Means The alkyl group preferably has 1 to 6 carbon atoms.

The term "acyl group" means a carbonyl group (1-C〇—) to which a hydrogen atom, an alkyl group or an aryl group is bonded. For example, formyl, acetyl, propanoyl And benzoyl. The alkyl group to be bonded preferably has 1 to 6 carbon atoms, and the aryl group to be bonded is preferably a phenyl group.

 "Heterocyclic group" refers to a monocyclic or bicyclic ring containing one or more atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom as constituent atoms of a ring structure. A substituent derived from an unsaturated, saturated or unsaturated heterocyclic compound, and these heterocyclic groups may be bonded at any position. Examples of the monocyclic heterocyclic group include, for example, pyrrole, furan, thiophene, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, imidazole, pyrazole, imidazolidine, virazolidine, oxazole, thiazole, oxazole, and thiadiazol. And a substituent derived from a monocyclic compound such as pyridin, dihydropyridine, tetrahydropyran, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, dioxane, pyran, and morpholine. Examples of the bicyclic heterocyclic group include substituents derived from a bicyclic heterocyclic compound such as benzofuran, indolizine, benzothiophene, indole, naphthyridine, quinoxaline, quinazoline, and chroman.

 The term "nitrogen-containing heterocyclic group" means that a heterocyclic group must contain at least one nitrogen atom, and at least one other atom selected from the group consisting of oxygen, nitrogen and sulfur It means a substituent derived from a saturated or unsaturated heterocyclic compound which may contain one or more. For example, pyrrole, pyrrolidine, imidazole, pyrazole, imidazolidine, virazolidine, oxazole, thiazole, oxaziazol, thiadiazole, pyridine, dihydric pyridine, piperidine, pyridazine, pyrimidine, virazine, piperazine, morpholine, thiomorpholine And the like.

 "Expression

One N X

(X means oxygen atom, sulfur atom, CH ₂ , CH—Y, Ν Η or Ν— 、, Υ Represents an alkyl group. )

 A 5- to 6-membered saturated heterocyclic group containing a nitrogen atom represented by the formula (The complex ring group is formed by adding an i-alkyl group or a ")" Means a substituent derived from a 5- to 6-membered saturated heterocyclic compound having at least one nitrogen atom as a constituent atom of the heterocyclic group. For example, there may be mentioned, for example, pyridine, imidazolidine, virazolidine, oxazolidine, thiazolidine, isoxazolidine, isothiazolidine, piperidine, piperazine, morpholine and thiomorpholine.

R ³ and R ⁴ together form

(In the formula, Q represents an oxygen atom, N—R ⁷ or CR ⁸ R ⁹ , and R ⁷ , R ⁸ and R ¹ represent an alkyl group or an acyl group.)

Forming a structure represented by means that the 6-position and 7-position portions have the following structure.

When R ⁴ and R ⁵ together form a three-membered ring with the carbon atoms to which they are attached, it means that the 7- and 8-positions have the following structure.

Next, each substituent in the general formula (I) will be described.

“Alkyl group” and “alkoxyl group” as substituents of a phenyl group of R ′ are Those with prime numbers 1 to 3 are preferred.

 The number of substituents of the phenyl group for R ′ is preferably 1 or 2, and the substitution position of the substituent is preferably the meta position.

 R ′ is preferably an unsubstituted phenyl group. Further, a phenyl group in which one or two fluorine atoms, chlorine atoms, methyl groups or methoxy groups are substituted at the amino position is also preferred.

As R ² , an alkyl group, an alkoxyl group and a cycloalkyl group are preferred.

As the “alkyl group” for R ² , a C ₆ alkyl group is preferable, and a methyl group, an ethyl group, and a propyl group are particularly preferable.

The “alkoxyl group” for R ² is preferably a C, to C ₆ alkoxyl group, particularly preferably a methoxy group or an ethoxy group.

As the “cycloalkyl group” for R ² , a C ₃ -C ₆ cycloalkyl group is preferred, and a cyclopropyl group is particularly preferred.

R ² is particularly preferably a methyl group, an ethyl group, a propyl group, a methoxy group, an ethoxyquin group or a cyclopropyl group.

R ³ is preferably a hydrogen atom (provided that R ⁴ is a hydrogen atom or a hydroxyl group, except that the bond between the carbon atom bonded to R ³ and the carbon atom bonded to R ⁴ is a single bond o) o

R ⁴ is preferably a halogen atom, an alkoxyl group, a hydrogen atom or a hydroxyl group (however, when R ⁴ is a hydrogen atom or a hydroxyl group, R ³ is a hydrogen atom, and a carbon atom to which R ³ is bonded is bonded to R ^4. Excluding those in which the bond between the carbon atoms is a single bond.

) 0

As the “halogen atom” for R ⁴ , a fluorine atom is preferable.

As the “alkoxyl group” for R ^4, a methoxy group is preferable.

Hydrogen atom as R ^4, a fluorine atom, a hydroxyl group or main butoxy group are particularly preferable (provided that when R ⁴ is a hydrogen atom or a hydroxyl group, with R ³ is a hydrogen atom, carbon atom and R ⁴ wherein R ³ is attached is bound Excluding those in which the bond between the carbon atoms is a single bond. And R ³ and R ⁴ together

(In the formula, Q represents an oxygen atom, N—R ⁷ or CR ⁸ R ⁹ , and R ⁷ , R ⁸ and R ¹ represent an alkyl group or an acyl group.)

The general formula (I-I 1) that formed the structure represented by

R ¹ FT

The structure represented by the formula (1) can also be mentioned as a preferable example.

As the structure represented by, it is preferable that Q is an oxygen atom.

R ³ is a methyl group, or R ³ combined with R ⁴ and R ⁵ to form a three-membered ring with the carbon atoms (7- and 8-positions) bonded thereto, That is, the 7th and 8th positions have the following structure

General formula (I-1 3)

The structure represented by the formula (1) can also be mentioned as a preferable example.

R ⁶ is preferably an alkyl group or an alkenyl group,

Examples of the alkyl group include a carboxyl group, an alkoxyl group, an aryloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, a cyano group, a hydroxyl group, an amino group, an alkylamino group, an acyl group, an aminoamino group, an acyloxy group, and an alkoxyl propylonyamino. Group, alkylthio group, alkylsulfinyl group, alkylsulfonyl group and formula

One N X

(X represents an oxygen atom, a sulfur atom, CH ₂ , CH—Y, Ν Η or Ν—Υ, and Υ represents an alkyl group.)

Represented by a saturated or unsaturated heterocyclic group containing a nitrogen atom having a size of 3 to 8 members (the heterocyclic group is an alkyl group on a carbon atom which is a constituent atom of the ring). And may have one or more groups selected from the group consisting of: The bonding position of the substituent may be any position of the alkyl group. As the alkyl group for R ⁶ , a C ₆ alkyl group is preferable, and a methyl group, an ethyl group, a propyl group, and a butyl group are particularly preferable.

The alkenyl group for R ⁵ is preferably a C ₂ -C ₆ alkenyl group, particularly preferably an aryl group.

As the substituent of the alkyl group represented by R ⁶ , an alkoxycarbonyl group, a hydroxyl group, a cyano group, an acyl group, an alkylamino group, an alkylthio group or a group represented by the formula

-N X

(X represents an oxygen atom, a sulfur atom, CH ₂ , CH—Y, Η Η, or Ν—Υ, Υ Υ, or (: ₃ means an alkyl group.)

A saturated or unsaturated heterocyclic group containing a nitrogen atom of the size of a 5-membered ring or a 6-membered ring (the heterocyclic group is an alkyl group on a carbon atom which is a constituent atom of the ring). Or a plurality thereof.) Is preferred.

 Most preferred substituents include those of the formula

A saturated or unsaturated heterocyclic group containing a nitrogen atom of the size of a 5-membered ring or a 6-membered ring (the heterocyclic group is an alkyl group on a carbon atom which is a constituent atom of the ring). pieces or have multiple.), with pyrrolidine, piperidine, Pipera Jin, morpholine, thiomorpholine, pyridine, 4-(C, substituents derived from -C ₃ alkyl) pin Perazine particularly preferable.

 In addition, a methyl group is preferable as the alkyl group substituted on a carbon atom which is a constituent atom of the ring of the heterocyclic group.

As R ⁶ , a compound represented by the formula — NX

(X represents an oxygen atom, a sulfur atom, CH ₂ , CH—Y, NH or N—Y, and Υ represents an alkyl group.)

 A saturated heterocyclic group containing a nitrogen atom having a size of a 5- to 6-membered ring represented by the formula (The complex-cyclic group has one or more alkyl groups on carbon atoms constituting the ring. And an alkyl group having 1 to 3 carbon atoms or an aryl group having

R ⁶ has, as a substituent, morpholine or thiomorpholine (the morpholine or thiomorpholine may have one or more methyl groups on a carbon atom as a constituent atom of the ring). Alkyl groups having 1 to 3 carbon atoms or aryl groups are most preferred.

As the “halogen atom” of the formulas ¹ and ² , a fluorine atom, a chlorine atom and a bromine atom are preferable.

As the “alkyl group” of the formulas ¹ and ² , a methyl group, an ethyl group and a propyl group are preferable.

As ¹ , a halogen atom and a hydroxyl group are preferable, and among the halogen atoms, a fluorine atom is particularly preferable.

The Zeta ^2, a halogen atom, a hydrogen atom or an alkyl group. Among the halogen atoms, a fluorine atom is particularly preferred. Among the alkyl groups, a methyl group is particularly preferred.

Most preferred as Zeta ¹ and Zeta ^2, Zeta ¹ is fluorine atom and Zeta ² is a combination of fluorine atom, Zeta ¹ is hydroxyl group, those Zeta ² is a combination of hydrogen atoms, Oh Rui Zeta ¹ is hydroxyl , Zeta ² can be mentioned those of a combination of a methyl group.

Preferred as ³ is an aryl group, a heterocyclic group or an alkenyl group.

As the “aryl group” in the above item ³ , a phenyl group is preferable.

As the “alkenyl group” of the formula ( ³ ), a 2-methyl-1-propenyl group is preferable.

The Zeta ³ heterocyclic group is preferably a monocyclic heterocyclic group, further, monocyclic A 5- or 6-membered heterocyclic group is preferable, and examples thereof include pyrrole, furan, thiophene, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, imidazole, pyrazole, imidazolidine, virazolidine, oxazole, and thiazol. And substituents derived from oxazine diazole, thiaziazole, pyridine, dihydropyridine, tetrahydric pyran, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, dioxane, pyran, morpholine and the like.

Among the heterocyclic group of Z ^3, a monocyclic 5- or 6-membered oxygen atom as a constituent atom of the heterocyclic group ring ring, the nitrogen atom or a sulfur atom especially one containing heterocyclic group a good Preferable examples include substituents derived from pyrrole, furan, thiophene, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, pyridine, dihydropyridine, tetrahydropyran, piperidine, pyran and the like.

Among the heterocyclic group of Z ^3, a monocyclic 5- or 6-membered oxygen atom in the heterocyclic group as a constituent atom of the ring structure of ring nitrogen atom or a heterocyclic group of the sulfur atom one containing unsaturated Is the most preferable, and specifically, a substituent derived from furan, pyridine or pyrrole is most preferable.

As Z ³ , a 2-methyl-1-propenyl group, a phenyl group, a furyl group, a pyridyl group, and a piperyl group are particularly preferred.

Z ⁴ is preferably an aryl group or an alkoxyl group.

As the “aryl group” for Z ⁴ , a phenyl group is preferred.

As the “alkoxyl group” for Z ⁴ , tertiary butyne is preferred.

As Z ⁴ , a phenyl group and a tertiary butkin group are particularly preferred.

 Note that

The bond in the dotted line of the formula is a double bond, and the general formula (I-I-2)

(1-2)

⁰ . >.

Those having the structure represented by R ¹ R ² can also be mentioned as preferable examples ₍

 In the present invention, the following configuration is preferable.

The configuration at the 3′-position to which the R ¹ substituent Z ³ is bonded is preferably a configuration having the same configuration as that of a natural taxol with a force including both configurations.

The taxol derivative of the present invention may be in a free form, but may be in the form of an acid addition salt or a salt of a carboxyl group. Examples of acid addition salts include inorganic salts such as hydrochloride, sulfate, nitrate, hydrobromide, hydroiodide and phosphate, or acetate, methanesulfonate And organic acid salts such as benzenesulfonate, toluenesulfonate, citrate, maleate, fumarate and lactate. Examples of the salt of the carboxyl group include, for example, alkali metal salts such as lithium salt, sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, ammonium salt, and triethylamine salt N-methyl. Any of inorganic salts and organic salts may be used, such as dalkamine salt and tris (hydroxylmethyl) aminomethane salt.

 The production method of the compound of the present invention will be described. In the reaction, the substituent is protected with a protecting group, if necessary, and the order of conversion of each substituent is not particularly limited.

1 6

Replacement form (Rule 26)

(2)

 16/1

Replacement form (Rule 26) [Wherein, R ⁴ ′ represents a hydroxyl group protected by a protecting group.

R ¹³ represents a hydrogen atom or a protecting group for a hydroxyl group.

R ⁶¹ is (as the substituent, if having a hydroxyl group, an amino group) R ^6, protected with R ⁶ or a protecting group refers to.

 Examples of the hydroxyl- or amino-protecting group include silyl-type protecting groups such as triethylsilyl group and tertiary-butylmethylsilyl group, and 2,2,2-trichloromouth ethoxycarbonyl, benzyloxycarbonyl, and benzyl groups. . First, a compound represented by the formula (1) (hereinafter, represented by the compound (1) and the compounds represented by other numbers is similarly represented) and acrolein in a solvent in the presence of a radical initiator are hydrogenated. Add tris (trimethylsilyl) silane, triptytin hydride or triphenyltin hydride to obtain compound (2).

 The solvent used in this reaction may be any solvent that is inert to the reaction, for example, toluene, benzene, and dioxane.

 Examples of the radical initiator used in the reaction include 2 ′, 2′-azobis (iso

1 6/2

Replacement form (Rule 26) Pentyronitrile), benzoyl peroxide, 2,2,6,6-tetramethyl-1-piperazinyloxy free radical, and the like. The amount of the radical initiator used may be a catalytic amount.

 The reaction may be carried out usually at a temperature of 50 ° C. to 150 ° C., preferably with stirring.

Acrolein is used in an amount of 5 to 50 equivalents based on the compound (1), and tris (trimethylsilyl) silane is used in an amount of about 2 to 10 equivalents based on the compound (1). Conversion of the compound (2), which is a 2-formylethyl group, to the compound (3) in which the 10-position is R ⁶ ′ may be performed by a usual organic chemical method.

 For example, a formyl group of a formylethyl group can be converted to a tertiary amine-bonded propionyl group by reacting the formyl group with a secondary amide under reducing conditions.

 Further, by reducing the formyl group with sodium borohydride or the like, it can be converted to an alcohol type hydroxyl group.

When R ⁶ ′ is an alcoholic hydroxyl group, it can be converted to an acyloxy group, an alkoxyl group, an amino group, an alkylamino group, an alkylthio group, a phenylzeleno group, or the like.

Furthermore, those R ^{6 1} becomes Amino groups can be converted Ashiruamino group, alkoxyl Cal Boniruamino group, an alkyl amino group.

Furthermore, those R ^{6 1} becomes Fuweniruzereno group can be converted to a substituent of Orefin type by the oxidation reaction, the substituent of the transformed Orefuin type can be converted into di-O Lumpur type by the oxidation reaction, also oxidized It can also be converted into a substituent having a reduced number of carbon atoms, for example, a formylmethyl group or a carboxylmethyl group by a chemical cleavage reaction.

In the case where R ^{6 1} becomes formylmethyl group, but may be converted as formyl group Horumiruechiru group, for example Echiru group bonded to more tertiary amines to react with a secondary amine and a reducing conditions Can be converted to

1 7

Replacement forms (Rule 26)

[Wherein, R ¹ , R ² , R ³ , R ″, R ⁵ , R ⁶ ′ and R ′ ³ are the same as described above. Z ¹¹ is a hydrogen atom, a halogen atom, a hydroxyl group protected by a protecting group, Means alkyl group,

Z ²¹ represents a hydrogen atom, a halogen atom, a hydroxyl group protected by a protecting group, or an alkyl group,

Z ³ 'denotes (as the substituent, a hydroxyl group, an amino group, if having a carboxyl group) Z ³ protected by a Z ³ or a protecting group, a,

z "is, tau, or (as the substituent, a hydroxyl group, an amino group, if having a carboxyl group) protected zeta ⁴ of a protecting group refers to.

 Examples of the hydroxyl and amino protecting groups include silyl protecting groups such as a triethylsilyl group and a tertiary butyldimethylsilyl group, an 11-ethoxystyl group, a 2,2,2-trichloroethoxycarbonyl group, and a benzyl group.

 Examples of the carboxyl-protecting group include a methyl group, an ethyl group, a benzyl group, a tertiary butyl group, and a 2,2,2-trichloroethyl group. ]

Compound (4) can be obtained by converting and deprotecting each substituent of compound (3) as necessary. For example, the 2-position of Benzoiru group C OR ', the 4-position of § cetyl group C OR ^2, the 7-position of the R "performs conversion such as to form a circularized structure with R ³ or R ⁵ The compound (4) having various substituents can be obtained The target compound (I) is obtained by reacting the compound (3) or the compound (4) with the compound (A), and finally removing the protecting group. Nara the R ⁶¹ to ^{R 6, Z u, Z 2} ', Z 31 and

 1 8

Replacement form (Rule 26) ⁴ ', respectively 2', as possible out to obtain by conversion to Z ^2, Z ³ and Z ^4.

 These conversions and deprotections can be performed using ordinary organic chemical methods.

As a method of converting the 2-position benzoyl group into COR ¹ , for example, after selectively hydrolyzing the 2-position benzoyl group according to the method described in the literature (Tetrahedron Lett., 35, 8931 (1994)), There is a method of acylation, and a compound in which R 'is other than a phenyl group can be obtained.

The 4-position of Asechiru groups as a method of converting a C OR ^2, for example, the literature (Ja - null, O blanking, Medi 'N'naru chemistry -... (J Med Chem ), 38, 2263 (1995)) , wherein There is a method in which the acetyl group at the 4-position is selectively hydrolyzed and then acylated according to the method described above, whereby a compound in which R ² is other than a methyl group can be obtained.

6-position of the R ^3, 7-position of the R ^4, 8-position of IT transformations There are a variety of methods depending on the type of R ^3, R ⁴ and R ^5.

For example, to obtain a compound (4) in which R ³ and R ⁴ are hydrogen atoms and the bond at the 6-position and the 7-position is a double bond, first, the protecting group of R ⁴¹ is removed and the 7-position is removed. Is converted into a compound that is a hydroxyl group, and then the hydroxyl group at the 7-position is converted into trifluoromethanesulfonyl by reacting, for example, trifluoromethanesulfonic anhydride in methylene chloride, and then in a solvent such as benzene or tetrahydrofuran. , 1,8-diazabicyclo [5,4,0] —7-indene.

 The converted substituent at the 6- or 7-position can be converted to an epoxy-type by an oxidation reaction using, for example, metabenzo-perbenzoic acid.

In the case of epoxy-type substituents, further various conversion reactions are possible. For example, one of R ^{3 and} R ⁴ is a hydroxyl group and the other is azide by a ring opening reaction using sodium azide or the like. It is also possible to obtain the compound (4) which is a group.

To obtain R ⁴ and a compound R ⁵ is a structure forming a connexion 3-membered ring such together (4), after the hydroxyl group removed 7-position a protecting group of IT ^1, triflic the hydroxyl group

1 9 The compound can be obtained by treating with silica gel in a solvent (acetonitrile, tetrahydrofuran, ethylene dichloride, etc., or a mixed solvent thereof) in a solvent.

To obtain the compound (4) in which R ⁴ is a fluorine atom, a compound in which the 7-position is a hydroxyl group is dissolved in a solvent (tetrahydrofuran, methylene chloride, ethyl ether, toluene, 1,1,1-dimethyxetane, or the like) (In a mixed solvent)) and treated with getylamino sulfate trifluoride.

To obtain a compound (4) in which R ^{4 is a} methoxy group, the protective group of R ⁴ ′ in the compound (3) is removed, a compound in which the 7-position is a hydroxyl group is synthesized, and dimethyl sulfoxide is used as a solvent. After reacting with acetic anhydride to perform methylthiomethylation, it can be obtained by desulfurization with Raney nickel in an alcoholic solvent.

The obtained compound (3) or (4), to obtain compound (I), firstly the compound (3) or 1 3-position substituents R ^'3 of the compound (4) is protected by a protecting group If it is present, it is deprotected to give a compound in which the 13-position is a hydroxyl group, and then the compound (A) is condensed with a base such as sodium hexamethyldisilazide-lithium hexamethyldisilazide, Finally, conversion and deprotection of each substituent may be performed.

Compound (1), which is a raw material for production, can be synthesized from 10-0-deacetylbaccatin III, and compounds in which R ⁴¹ is a hydroxyl group protected by a triethylunyl group are known (Tetrahedron Lett., 34, 4921 (1993)).

 Compound (A), which is a raw material for production, can be synthesized according to the method described in the literature (Tetrahedron Lett., 34, 4149 (1993)).

 The compound of the present invention can be used for the treatment of various cancers such as, for example, lung cancer, gastrointestinal cancer, ovarian cancer, uterine cancer, breast cancer, liver cancer, head and neck cancer, blood cancer, kidney cancer, Kogan tumor. The compound of the present invention can be administered as various injections such as intravenous injection, intramuscular injection and subcutaneous injection, or by various methods such as oral administration and transdermal administration. Among these administration methods, intravenous administration by an aqueous preparation and oral administration are preferred. Aqueous preparations can be prepared by preparing a pharmacologically acceptable acid and an acid adduct, or by using an alkali metal salt such as sodium. In the case of oral administration, it may be in a free form or in a salt form.

2 0 As for the preparation method of the preparation, an appropriate preparation is selected according to the administration method, and the preparation can be prepared by various commonly used preparation methods. Among the dosage forms of the antitumor agent of the present invention, examples of oral preparations include tablets, powders, granules, capsules, solutions, syrups, elixirs, oily or aqueous suspensions, and the like. In the case of injections, stabilizers, preservatives, dissolution aids, etc. can be used in the formulation. A solution that may contain these scavengers and the like may be stored in a container, and then freeze-dried or the like to prepare a solid preparation as a preparation ready for use.

 Liquid preparations include solutions, suspensions, emulsions, and the like. When preparing these preparations, suspending agents, emulsifiers, and the like can also be used as additives. The compound of the present invention can be used for the treatment of cancer in mammals, particularly in humans. When administered to humans, it is preferably administered once a day and repeated at appropriate intervals.

The dose is preferably in the range of about 0.5 to 50 mg, preferably about 1 to 20 mg per 1 m ^{2 of} body surface area.

 Next, examples and reference examples will be described in detail.

 The following abbreviations may be used in the examples.

TMS: trimethylsilyl group, Boc: tert-butoxycarbonyl group, TBS: tert-butyldimethylsilyl group, Bz: benzoyl group, Ac: acetyl group, TES: triethylsilyl group, Troc: 2,2,2-trichloro Mouth ethoxyquin carbonyl group, Tf: trifluoromethanesulfonyl group, DMS: dimethylsilyl group, TIPS: triisopropylsilyl group, Me: methyl group, Et: ethyl group, MTM: methylthiomethyl group

twenty one

Replacement form (Rule 26) BEST MODE FOR CARRYING OUT THE INVENTION Reference Example 1

2 1/1 Replacement paper (Rule 26) Step 1: cis-3-methyl-4-phenyl-3- (trimethylsilyl) oxy-2-azetidinonelithium bis (trimethylsilyl) amide (1 M solution in tetrahydrofuran) 16.9 ml of the solution was brought to -78 ° C. After cooling, 15 ml of a furan solution of benzaldehyde (1.55 g) in tetrahydrofuran was added dropwise under nitrogen. After 5 minutes, the mixture was stirred at 0 ° C. for 30 minutes. Subsequently, 2.26 ml of trimethylsilane chloride was added, and the mixture was stirred for 30 minutes. On the other hand, 2.22 ml of diisopropylamine in 25 ml of a tetrahydrofuran solution was ice-cooled, n-butyllithium (1.70 M hexane solution, 9.95 ml) was added dropwise, and the mixture was stirred for 15 minutes. Then, the mixture was cooled to -78 ° C, and a solution of 2.48 g of methyl 2- (trimethylsilyloxy) propionate in 25 ml of tetrahydrofuran was added dropwise and stirred for 15 minutes. The imine solution prepared above was added dropwise using a force nebulizer, and the temperature was raised to room temperature overnight. To the reaction solution was added a saturated aqueous solution of ammonium chloride, extracted with ethyl acetate, washed with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: ethyl acetate: hexane == 1: 5 to 1.3 (v / v)) to obtain 0.98 g of the title compound as pale yellow crystals.

Ή-NR (CDCh / TMS) 5 (ppm):

 -0.07 (s, 9H), 1.66 (s, 3H), 4.51 (s, 1H), 6.10 (br, 1H), 7.28-7.39 (m, 5H). Step 2: cis-l- (tert-butoxycarbo Nil) -3-Methyl-4-phenyl-3- (trimethylsilyl) oxy-2-azetidinone

 860 mg of the compound obtained in the above step 1 was dissolved in 8.6 ml of tetrahydrofuran, 0.95 ml of di-tert-butyl dicarbonate and 20 mg of 4-dimethylaminopyridine were added under ice cooling, and the mixture was stirred at room temperature for 1 hour. After evaporating the solvent under reduced pressure, the obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate: hexane = 1: 1 10 (v / v)) to obtain 1.01 g of the title compound as colorless crystals As obtained.

Ή-NMR (CDCh / TMS) 5 (ppm):

 -0.07 (s, 9H), 1.40 (s, 9H), 1.67 (s, 3H), 4.73 (s, 1H), 7.21-7.37 (m, 5H).

twenty two

Replacement form (Rule 26) Reference example 2

2 2/1 Replacement Form (Rule 26) Step l: cis-4- (p-fluorophenyl) -3-methyl-3- (trimethylsilyl) oquin-2-azetidinone

 In the same manner as in Step 1 of Reference Example 1, the reaction was carried out using P-fluorobenzaldehyde instead of benzaldehyde to obtain the title compound as pale yellow crystals.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 -0.05 (s, 9H), 1.64 (s, 3H), 4.49 (s, 1H), 6.15 (br, 1H), 7.04-7.26 (m, 4H). Step 2: cis-l- (tert-butoxycarbo Nyl) -4-p-fluorophenyl-3-methyl-3- (trimethylsilyl) oxy-2-azetidinone

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 2 of Reference Example 1 to obtain the title compound as colorless crystals.

1 H-NMR (CDC / TMS) <5 (ppm):

 -0.04 (s, 9H), 1.41 (s, 9H), 1.66 (s, 3H), 4.71 (s, 1H), 7.03-7.22 (m, 4H). Reference Example 3

twenty three

Replacement form (Rule 26) Step 1: cis-3- (tert-butyldimethylsilyl) oxy-3-methyl-4-phenyl'-2-azetidinone

 In the same manner as in Step 1 of Reference Example 1, 2- (tert-butyldimethylsilyloxy) propionic acid methyl ester was used in place of 2- (trimethylsilyloxy) propionic acid methyl ester to give the title compound as a white solid. .

Melting point: 102-104 ° C (recrystallized from pentane, colorless prism)

Ή-NMR (CDCh / TS) 5 (ppm):

 -0.17 (s, 3H), 0.08 (s, 3H), 0.51 (s, 9H), 1.64 (s, 3H), 4.53 (s, 1H), 6.05 ( br, lH), 7.24-7.36 (m, 5H).

Step 2: cis-1- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyl)

2 3/1

Replacement paper (Kaikai IJ26) Oxy-3-methyl_4-phenyl-2-azetidinone

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 2 of Reference Example 1 to obtain the title compound as a white solid.

Melting point: 93 ° C (recrystallized from pentane, colorless prism)

Ή-NMR (CDCl ₃ / TS) (5 (ppm):

 0.01 (s, 3H), 0.05 (s, 3H), 0.51 (s, 9H), 1.44 (s, 9H), 1.65 (s, 3H), 4.77 (s, 1H), 7.16-7.35 (m, 5H) .

Reference example 4

Two

twenty four

Replacement forms (Rule 26) Step 1: cis-3-methyl-4-phenyl-3- (triethylsilyl) oxy-2-azetidinone

 In the same manner as in Step 1 of Reference Example 1, 2- (triethylsilyl) oxypropionic acid methyl ester was used in place of 2- (trimethylsilyl) oxypropionic acid methyl ester to carry out the reaction to obtain the title compound as a white solid.

Ή-NMR (CDCh / TS) (5 (ppm):

 0.40-0.46 (m, 6H), 0.72 (t, 9H, J = 7 Hz), 1.66 (s, 3H), 4.52 (s, 1H), 6.15 (br , 1H), 7.24-7. 37 (m, 5H).

Step 2: (3R, 4S) -3-methyl-4_phenyl-3- (triethylsilyl) oxy-2-azetidinone

25 mg of 10% 2-propanol / hexane (v / v) was dissolved in 500 mg of the compound obtained in step 1 above, and the mixture was dissolved in an optically active column (CHIRALCEL 0D, elution solvent; 10% 2-propanol / hexane (v / v) v))) to give 3S, 4R form (220 mg) as the first peak and the desired 3R, 4S form (215 mg) as the second peak, as colorless crystals.

^{_{[A] D 2 4 + 77}} ° (c 0. 09, ethanol).

2 4/1

Replacement form (Rule 26) Ή-NMR (CDC / TMS) <5 (ppm):

 0.40-0.46 (m, 6H), 0.72 (t, 9H, J2 7 Hz), 1.66 (s, 3H), 4.52 (s, 1H), 6.15 (br, 1H), 1.24-7.37 (m, 5H) .

Step 3: (3R, 4S) -l- (tert-butynecarbonyl) -3-methyl-4-phenyl-3- (triethylsilyl) oxy-2-azetidinone

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 2 of Reference Example 1 to obtain the title compound as colorless crystals.

[a] _D ²⁴ + 96 ° (c 0.13, ethanol).

Ή-NMR (CDC / TMS) 5 (ppm):

 0.45 (q, 6H, J = 8 Hz), 0.72 (t, 9H, J = 8 Hz), 1.43 (s, 9H),

1.67 (s, 3H), 4.80 (s, 1H), 7.19-7.34 (m, 5H).

Reference example 5

twenty five

Replacement form (Rule 26) Step 1: cis-3-methyl-4- (4-tolyl) _3- (trimethylsilyl) oxy-2-azetidinone

 In the same manner as in Step 1 of Reference Example 1, the reaction was carried out using 4-tolualdehyde instead of benzaldehyde to obtain the title compound as a white solid.

Ή-NMR (CDCh / TMS) δ (ppm):

 -0.0.6 (s, 9H), 1.64 (s, 3H), 2.36 (s, 3H), 4.47 (s, 1H),

6.06 (br, 1H), 7.16 (s, 4H).

Step 2: (3R, 4S) -3-Methyl-4- (4-tolyl) -3- (trimethylsilyl) oxy-2--2-azetidinone

 The compound obtained in the above Step 1 was separated in the same manner as in Step 2 of Reference Example 4 to obtain the title compound as colorless crystals.

Melting point: 55-56 ° C.

[] ^{2 4} + 58.0 ° (c 1.00, ethanol).

2 5/1

Replacement form (Rule 26) Ή-NR (CDC / TMS) δ (ppm):

 -0.06 (s, 9H), 1.64 (s, 3H), 2.36 (s, 3H), 4.47 (s, 1H),

6.06 (br, 1H), 7.16 (s, 4H).

Step 3: (3R, 4S) -1- (tert-butoxycarbonyl) -3-methyl-4- (4-tolyl) -3- (trimethylsilyl) oxy-2-azetidinone

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 2 of Reference Example 1 to obtain the title compound as colorless crystals.

Melting point: 75-78 ° C.

[Hi]. ²⁴ +103 ° (c 1.25, ethanol).

Ή-NMR (CDCh / TMS) δ (ppm):

 -0.06 (s, 9H), 1.40 (s, 911), 1.65 (s, 3H), 2.35 (s, 3H), 4.69 (s, 1H), 7.10-7.16 (m, 4H).

Example 1

2 6

Replacement form (Rule 26)

Process 1: 10-aryl-10-deacetoxypaccatin III

 10-aryl-10-deacetoxy-7-0-triethylsilylpaccatin III 360 m was dissolved in 4.0 ml of pyridine. After adding 1.0 ml of hydrogen fluoride pyridine at C and stirring at room temperature for 8 hours, the reaction solution was poured into a mixed solution of 20 ml of stirred ethyl acetate and 60 ml of ice water and separated, and the aqueous layer was extracted with 20 ml of ethyl acetate. . Combine the organic layers and add saturated aqueous sodium bicarbonate

26/3 Replacement Form (Rule 26) After washing with a solution and drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue obtained was purified by reprecipitation (form-form-ether-hexane) to give 267 mg of the title compound as a colorless amorphous solid, and silica gel thin layer chromatography was obtained from the residue obtained by concentrating the mother liquor. (Developing solvent; hexane: ethyl acetate = 1: 1 (v / v)) to give 20.8 nig of the title compound as a colorless amorphous solid.

 Ή-NMR (CDC / TMS) <5 (ppm):

 1.06 (3H, s), 1.11 (3H, s), 1.44 (1H, d, J = 7.3Hz), 1.64 (3H, s),

 1.65 (1H, s), 1.80 (1H, ddd, J = 2.4Hz, 11.2Hz, 14.2Hz), 1.92 (3H, d, J = l.0Hz), 2.17-2.42 (3H, m), 2.28 (3H , s), 2.57 (1H, ddd, J = 6.4Hz, 9.8Hz, 14.2Hz), 2.88-2.98 (lH, m), 3.93 (1H, dd, J = 6.4Hz, 7.8Hz), 4.11 (1H, d, J = 7.3Hz), 4.19 (1H, d, J = 8.4Hz), 4.31 (1H, d, J = 8.4Hz), 4.30-4.42 (1H, m),

 4.86 (lH, s), 4.95-5.05 (2H, m), 5.12 (1H, dd, J = 16.9Hz, 1.7Hz),

 5.63 (1H, d, J = 7.3Hz), 5.73-5.87 (1H, m), 7.48 (2H, t, J = 7.8Hz),

7.60 (1H, t, J = 7.8Hz), 8.11 (2H, d, J = 7.8Hz).

Step 2: 10-aryl-10-deacetoxy-7-0- (2,2,2-trichloroethoxycarbonyl)

 Dissolve 280 m of the compound obtained in the above step 1 in 8.0 ml of pyridine, add 75.0 ml of 2,2,2-trichloromethyl ethyl chloroformate at 0 ° C and stir for 2 hours. The mixture was poured into a mixture of 20 ml of ethyl and 60 ml of ice water, and separated, and the aqueous layer was extracted with 20 ml of ethyl acetate. The organic layers were combined, washed with a 1N aqueous hydrochloric acid solution (50 ml), a saturated aqueous solution of sodium bicarbonate (50 ml) and a saturated aqueous solution of sodium chloride (50 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent; hexane: ethyl acetate = 1: 1 (v / v)) to obtain 360 mg of the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.06 (3H, s), 1.19 (3H, s), 1.78 (3H, s), 1.98 (3H, d, J = 1.5Hz),

1.98-2.08 (lH, m), 2.18-2.35 (3H, m), 2.30 (3H, s),

2.64 (1H, ddd, J = 7.3Hz, 9.8Hz, 14.2Hz), 2.78-2.87 (1H, m),

4.09 (1H, t, J = 7.8Hz), 4.19 (1H, d, J = 5.9Hz),

2 7 4.20 (1H, d, J = 8.3Hz), 4.33 (1H, d, J = 8.3Hz), 4.68 (1H, d, J = ll.7Hz),

 4.75 (1H, d, J = ll.7Hz), 4.85 (1H, s), 4.95-5.00 (2H, m),

 5.08 (1H, dd, J = 16.9Hz, 1.7Hz), 5.53 (1H, dd, J = 7.1Hz, 11.0Hz),

 5.68-5.80 (1H, m), 7.48 (2H, t, J = 7.8Hz), 7.61 (1H, t, J = 7.8Hz),

8.10 (2H, d, J = 7.8Hz).

Step 3: 10-aryl-10-deacetoxy-7-0- (2,2,2-trichloroethoxycarboninole) -13-0-triethylsilylpaccatin III

 Dissolve 360 m of the compound obtained in the above step 2 in 15 ml of methylene chloride, add -100 ml of 2,6-lutidine and 165 ml of triethylsilyltrifluoromethanesulfonate at -50 ° C, and stir for 1.5 hours. After adding 150 ml of 1,6-lutidine and 240 ml of triethylsilyltrifluoromethanesulfonate and stirring for 2 hours, 50 ml of saturated aqueous sodium hydrogen carbonate and 50 ml of ethyl acetate were added to the reaction mixture, and the mixture was separated. The aqueous layer was extracted with 20 ml of ethyl acetate. did. The organic layers were combined, washed with 50 ml of saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel column chromatography (eluent; hexane: ethyl acetate = 5: 1 (v / v)) to obtain 285 mg of the title compound as a colorless transparent glassy substance.

_{Ή-NR (CDC1 3 / TMS} ) (5 (ppm):

 0.60-0.73 (6H, m), 1.02 (9H, t, J2 7.3Hz), 1.09 (3H, s), 1.12 (3H, s),

1.61 (1H, s), 1.77 (3H, s), 1.93 (3H, d, J = l.5Hz), 1.99-2.14 (2H, m),

2.20-2.33 (2H, m), 2.30 (3H, s), 2.62 (1H, ddd, J = 6.8Hz, 9.3Hz, 14.2Hz), 2.77-2.86 (lH, m), 4.08 (1H, t, J = 6.8Hz), 4.12 (1H, d, J = 7.1Hz),

4.20 (1H, d, J = 8.1Hz), 4.32 (1H, d, J = 8.1Hz), 4.67 (1H, d, J2 11.7Hz),

 4.75 (1H, d, J = ll.7Hz), 4.91 (1H, dd, J = 7.3Hz, 8.3Hz), 4.94-5.02 (2H, m),

5.06 (1H, dd, J = l.5Hz, 17.1Hz), 5.54 (1H, dd, J = 7.1Hz, 11.1Hz),

 5.64 (1H, d, J = 7.1Hz), 5.68-5.79 (1H, m), 7.48 (2H, t, J2 7.3Hz),

7.61 (1H, t, J = 7.3Hz), 8.09 (2H, d, J = 7.3Hz).

Step 4: 10-aryl-10-deacetoxy-13-0-triethylsilylpaccatin III 285 m of the compound obtained in the above step 3 is dissolved in 30 ml of ethyl acetate, and 2.80 g of zinc powder and 1.90 ml of acetic acid are added at room temperature. After stirring at room temperature for 5 minutes, the reaction mixture was filtered and filtered.

2 8 150 ml of a saturated aqueous solution of sodium bicarbonate was added to the solution, and the mixture was separated. The aqueous layer was extracted with 30 ml of ethyl acetate. The organic layers were combined, washed with 50 ml of saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; hexane: ethyl acetate = 3: 1 (v / v)) to give 215 m of the title compound as a colorless amorphous solid.

 Ή-NR (CDCh / TMS) (5 (ppm):

 0.60-0.75 (6H, m), 1.01 (9H, t, J = 7.8Hz), 1.10 (3H, s), 1.13 (3H, s),

1.62 (3H, s), 1.65 (1H, s), 1.75-1.85 (lH, m), 1.87 (3H, d, J = l. 0Hz),

 2.10 (1H, dd, J = 8.3Hz, 15.6Hz), 2.20-2.40 (2H, m), 2.29 (3H, s),

2.50-2.63 (1H, m), 2.88-2.98 (1H, m), 3.89 (1H, t, J = 7.1 Hz),

 4.02 (lH, d, J = 7.1 Hz), 4.19 (1H, d, J = 8.8 Hz), 4.28-4.40 (1H, m),

 4.30 (1H, d, J = 8.8Hz), 4.90 (1H, dd, J = 7.1Hz, 8.3Hz), 4.95-5.05 (2H, m),

5.09 (1H, d, J = 17.1 Hz), 5.63 (1H, d, J = 7. IH2), 5.73-5.87 (lH, m),

 7.47 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz), 8.09 (2H, d, J = 7.3Hz).

Step 5: 10-aryl-10-deacetoxy-13-0-triethylsilyl-7-0-0-trifluo mouth methanesulfonylbaccatin I I I

 Dissolve 205 mg of the compound obtained in the above step 4 in 15 ml of methylene chloride, add 5.0 ml of pyridine and 263 ml of trifluorosulfonic anhydride at 0 ° C, stir at room temperature for 1.5 hours, and react. The solution was poured into a stirred mixture of 50 ml of ethyl acetate and 150 ml of ice water, and the mixture was separated. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with 50 ml of a saturated aqueous sodium hydrogen carbonate solution and 50 ml of a saturated saline solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluting solvent; chloroform: ethyl acetate = 40: 1 to 10: 1 (v / v)) to give 226 mg of the title compound as a colorless non-colored liquid. Obtained as a crystalline solid.

Ή-NMR (CDC / TMS) (5 (ppm):

 0.60-0.73 (6H, m), 1.01 (9H, t, J = 7.8Hz), 1.12 (3H, s), 1.15 (3H, s),

1.59 (1H, s), 1.79 (3H, s), 1.91 (3H, d, J = l.5Hz),

 2.11 (1H, dd, J = 8.3Hz, 15.1Hz), 2.16 2.28 (2H, m), 2.31 (3H, s),

2.40-2.50 (1H, m), 2.74-2.84 (lH, m), 2.83-2.90 (1H, m),

2 9 4.08-4.16 (2H, m), 4.18 (1H, d, J = 8.3Hz), 4.33 (1H, d, J = 8.3Hz), 4.88-4.98 (2H, m), 5.02 (1H, dd, J = 2.0Hz, 9.8Hz),

 5.09 (1H, dd, J = 1.5Hz, 17.1Hz), 5.60 (1H, dd, J = 7.3Hz, 10.7Hz),

5.65 (lH, d, J = 6.8Hz), 5.68-5.80 (1H, m), 7.48 (2H, t, J = 8.3Hz),

7.62 (1H, t, J = 8.3Hz), 8.08 (2H, d, J = 8.3Hz).

Step 6: 10-aryl-10-deacetoxy-7-deoxy-6,7-didehydro-13-0-tritylsilylpaccatin III

 Dissolve 226 mg of the compound obtained in the above step 5 in 5.0 ml of tetrahydrofuran, add 0.50 ml of 1,8-diazabicyclo [5.4.0] -7-pandecene at room temperature, heat under reflux at room temperature for 3 hours, allow to cool, and reduce the pressure. The lower solvent was distilled off. The obtained residue was purified using silica gel column chromatography (elution solvent; benzene: ethyl acetate = 3: 1 (v / v)) to obtain 180 mg of the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 0.58-0.78 (6H, m), 1.00 (9H, t, J = 7.8Hz), 1.08 (3H, s), 1.15 (3H, s),

1.70 (lH, s), 1.78 (3H, d, J = 1.5 Hz), 1.82 (3H, s),

 2.10 (1H, dd, J = 8.6Hz, 14.8Hz), 2.17-2.30 (1H, m),

 2.27 (1H, dd, J = 8.3Hz, 14.8Hz), 2.28 (3H, s), 2.93-3.04 (1H, m),

 3.16 (1H, t, J = 7.lHz), 4.18 (1H, d, J = 6.3Hz), 4.28 (1H, d, J = 7.8Hz),

 4.43 (1H, d, J = 7.8Hz), 4.92 (1H, t, J = 7.6Hz), 5.01 (1H, dd, J = 1.5Hz, 9.3Hz),

5.05-5.13 (1H, m), 5.12 (1H, d, J = 5.9Hz), 5.73 (1H, d, J = 9.8Hz),

 5.79 (lH, d, J = 6.3Hz), 5.76-5.88 (lH, m), 6.01 (1H, dd, J = 5.9, 9.8Hz),

 7.49 (2H, t, J-7.8Hz), 7.62 (1H, t, J = 7.8Hz), 8.14 (2H, d, J-7.8Hz).

Step 7: 10-aryl-10-deacetoxy-7-deoxy-6,7-didedropakcatin III 28.0 mg of the compound obtained in the above step 6 is dissolved in 1.0 ml of pyridine, and 0.50 ml of pyridine hydrofluoride is added at 0 ° C. After the mixture was stirred at room temperature for 7 hours, the reaction solution was poured into a mixed solution of 10 ml of stirred ethyl acetate and 20 ml of ice water, and separated, and the aqueous layer was extracted with 10 ml of ethyl acetate. The organic layers were combined, washed with a saturated aqueous sodium bicarbonate solution (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel thin-layer chromatography (developing solvent; hexane: ethyl acetate = 1: 1 (v / v)) to obtain a target.

3 0 16.9 mg of the title compound was obtained as a colorless amorphous solid. -'IHVMR (CDC / TMS) 5 (ppm):

 1.08 (3H, s), 1.09 (3H, s), 1.73 (1H, s), 1.82 (3H, s),

 1.84 (3H, d, J 1.5Hz), 2.02 (1H, d, J = 5.4Hz), 2.18-2.30 (3H, m),

 2.30 (3H, s), 2.93-3.02 (lH, m), 3.68 (1H, t, J = 7.1Hz),

 4.29 (1H, d, J = 6.9Hz), 4.31 (1H, d, J = 8.3Hz), 4.42 (1H, d, J = 8.3Hz),

4.81-4.90 (1H, m), 4.98-5.05 (1H, m), 5.11 (1H, d, J = 5.4Hz),

 5.07-5.14 (1H, m), 5.74 (1H, d, J = 10.2Hz), 5.80 (1H, d, J = 6.9Hz),

 5.78-5.90 (lH, m), 6.02 (1H, dd, J = 5.4Hz, 10.2Hz), 7.49 (2H, t, J = 8.3Hz), 7.62 (1H, t, J = 8, 3Hz), 8.15 (2H, d, J = 8.3Hz).

Step 8: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylphenylion] -10- Deacetoxy-7-doxy-6,7-didedropropacatin II 1

 Dissolve 16.5 mg of the compound obtained in the above step 7 in 2.0 ml of tetrahydrofuran, add 40.0 ml of lithium bis (trimethylsilyl) amide (1 M tetrahydrofuran solution) at -45 ° C, stir for 30 minutes, and then add (3R, 4S ) -l- (tert-Butoxycarbonyl) -3- (tert-butyldimethylsilyl) oxy-4- phenyl-2-azetidinone A solution of 23.0 m of 1.0 ml of tetrahydrofuran was added dropwise at 0 ° C. After stirring for an hour, 10 ml of an aqueous solution of saturated ammonium chloride and 10 ml of ethyl acetate were added to the reaction solution, and the mixture was separated. The aqueous layer was extracted with 10 ml of ethyl acetate. The organic layers were combined, washed with saturated saline (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel thin-layer chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (v / v)) to obtain 27.8 mg of the title compound as a colorless transparent glassy substance.

Ή-NMR (CDC / TS) 5 (ppm):

 -0.35 (3H, s), -0.11 (3H, s), 0.75 (9H, s), 1.12 (3H, s), 1.27 (3H, s),

1.32 (9H, s), 1.65 (1H, s), 1.70 (3H, d, J = 1.0Hz), 1.86 (3H, s),

 2.16 (1H, dd, J = 7.8Hz, 14.9Hz), 2.18-2.27 (1H, m),

 2.43 (1H, dd, J = 9.8Hz, 14.9Hz), 2.56 (3H, s), 2.99-3.06 (1H, m),

 3.65 (1H, t, J = 6.8Hz), 4.21 (1H, d, J 6.8Hz), 4.34 (1H, d, J = 8.3Hz),

3 1 4.44 (1H, d, J = 8.3Hz), 4.50 (1H, s), 5.04 (1H, d, J = 9.8Hz),

 5.21 (1H, d, J = 5.5Hz), 5.22 (1H, dd, J = 1.5Hz, 17.1Hz), 5.32 (1H, d, J = 9.3Hz),

5.46 (1H, d, J = 9.3Hz), 5.76 (1H, d, J = 9.8Hz), 5.86 (1H, d, J = 6.8Hz),

 5.78-5.90 (lH, m), 6.03 (1H, dd, J = 5.5Hz, 9.8Hz), 6.36 (1H, t, J = 8.6Hz),

7.50 (2H, t, J = 7.3Hz), 7.60 (1H, t, J = 7.3Hz), 8.17 (2H, d, J = 7.3Hz).

Step 9: 10-aryl-13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-7-deoxy _6,7-didedropropachatin III

 Dissolve 27.0 mg of the compound obtained in the above step 8 in 2.0 ml of pyridine, add 0.50 ml of pyridine hydrofluoride at 0 ° C, stir at room temperature for 4 hours, then stir the reaction solution with 10 ml of stirred ethyl acetate and 20 ml of ice water. The mixture was poured into a mixture of the above and separated, and the aqueous layer was extracted with 10 ml of ethyl acetate. The organic layers were combined, washed with a saturated aqueous solution of sodium bicarbonate (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 1: 1 (v / v)) to obtain 22.3 mg of the title compound as a colorless amorphous solid. .

Ή-NMR (CDC / TMS) (5 (ppm):

 1.12 (3H, s), 1.24 (3H, s), 1.33 (9H, s), 1.64 (3H, s), 1.82 (1H, s),

 1.84 (3H, s), 2.18-2.40 (3H, m), 2.38 (3H, s), 2.93-3.04 (1H, m),

 3.32 (lH, d, J-5.4Hz), 3.65 (1H, t, J = 7.1Hz), 4.17 (1H, d, J = 6.4Hz),

 4.32 (1H, d, J = 8.3Hz), 4.42 (1H, d, J = 8.3Hz), 4.60 (1H, s),

 5.03 (1H, d, J = 9.8Hz), 5.08 (1H, d, J = 5.4Hz), 5.11 (1H, dd, J = l.5Hz, 17.1Hz),

5.28 (lH, d, J = 9.8Hz), 5.40 (1H, d, J = 9.8Hz), 5.74 (1H, d, J = 9.8Hz),

5.84 (1H, d, J = 6.4Hz), 5.77-5.87 (1H, m), 6.02 (1H, dd, J = 5.4Hz, 9.8Hz),

6.21 (1H, t, J = 8.6Hz), 7.51 (2H, t, J = 8.3Hz), 7.62 (1H, t, J = 8.3Hz),

8.15 (2H, d, J = 8.3Hz).

Step 10: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3--3-phenylpropionyl] -10-deacetoxy-7-deoxy-6,7 -Didehydro-10- (2-morpholinoethyl) paccatin III

 22.0 mg of the compound obtained in the above step 9 was dissolved in 2.0 ml of tetrahydrofuran, and

3 2 After adding 1.0 ml of aqueous solution of osmium tetroxide (0.40 M aqueous solution) and 50.0 m of N-methylmorpholine-N-oxide at room temperature, the mixture was stirred at room temperature for 1 hour. To the reaction solution, 10 ml of ethyl acetate and 15 ml of a 10% aqueous sodium thiosulfate solution were added, and the mixture was stirred for 30 minutes and separated, and the aqueous layer was extracted with 10 ml of ethyl acetate. The organic layers were combined, washed with a saturated aqueous sodium bicarbonate solution (10 ml) and a saturated saline solution (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain a residue (23.0 mg). This residue was dissolved in 2.0 ml of tetrahydrofuran, 2.0 ml of methanol, 2.0 ml of water and 69.5 mg of sodium periodate were added at room temperature, and the mixture was stirred at room temperature for 1 hour. 10 ml of ethyl acetate and 10 ml of water were added to the reaction solution, and the mixture was stirred for 30 minutes and separated, and the aqueous layer was extracted with 10 ml of ethyl acetate. The organic layers were combined, washed with 10 ml of a saturated saline solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 22.7 mg of a residue. This residue was dissolved in 3.0 ml of ethanol, and 24.0 ml of morpholine, 15.5 ml of acetic acid and 17.0 mg of sodium cyanoborohydride were added at room temperature, and the mixture was stirred at room temperature for 1 hour. To the reaction solution were added 10 ml of a saturated aqueous solution of sodium bicarbonate, 10 ml of ethyl acetate and 10 ml of water, and the mixture was stirred for 30 minutes and separated, and the aqueous layer was extracted with 10 ml of ethyl acetate. The organic layers were combined, washed with saturated saline (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel thin layer chromatography-I (developing solvent; black form: acetone = 7: 3 (v / v)) to give 22.7 mg of the 1,4-dioxane title compound as a colorless solid. As obtained.

Ή-NMR (CDC / TMS) 5 (ppm):

 1.10 (3H, s), 1.22 (3H, s), 1.33 (9H, s), 1.44-1.55 (1H, m), 1.72 (3H, s),

1.83 (3H, s), 2.23 (1H, dd, J = 8.6Hz, 14.9Hz), 2.30-2.60 (8H, m),

 2.39 (3H, s), 3.68 (4H, t, J 二 4.7Hz), 3.78 (1H, dd, J = 4.9Hz, 6.8Hz),

 4.19 (1H, d, J = 6.6Hz), 4.31 (1H, d, J = 8.1Hz), 4.42 (1H, d, J-8.1Hz),

 4.60 (lH, s), 5.11 (1H, d, J = 5.7Hz), 5.27 (1H, d, J = 9.3Hz),

 5.41 (1H, d, J = 9.3 Hz), 5.72 (1H, d, J = 9.8 Hz), 5.83 (1H, d, J-6.6 Hz),

 6.02 (1H, dd, J2 5.9Hz, 9.8Hz), 6.18 (1H, t, J = 8.6Hz), 7.51 (2H, t, J2 7.3Hz),

7.62 (1H, t, J = 7.3Hz), 8.16 (2H, d, J = 7.3Hz).

Melting point: 202.5-206.5 ° C

Example 2

3 3

TES〇 \\, TESQ \, TESO \,

 HO OBz OAc DMSO OBz OAc DMSO OBz OH

C

t

 Step 3 Step 4

TESO ,,, 'HO ,,,

HO-OBz ⁰ 0

34/1 Replacement paper (Kaikai IJ26) Step 1: 10-aryl-10-deacetoxy-7-deoxy-6,7-didehydro-1-0-dimethylenelrill-13-0-triethylsilylpaccatin III

 Dissolve 150 m of the compound obtained in Step 6 of Example 1 in 3.0 ml of N, N-dimethylformamide, add 62.0 mg of imidazole and 100 ml of dimethylsilane chloride at 0 ° C, and stir for 20 minutes. 20 ml of a saturated aqueous solution of sodium bicarbonate and 10 ml of ethyl acetate were added to the liquid, and the mixture was separated. The organic layers were combined, washed with 10 ml of water and 10 ml of saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (v / v)) to give 162 mg of the title compound as a colorless amorphous solid. Obtained.

 Ή-NMR (CDC / TS) (5 (ppm):

 -0.23 (3H, d, J = 2.9Hz), 0.09 (3H, d, J = 2.9Hz), 0.60-0.75 (6H, m),

 1.03 (9H, t, J = 7.8Hz), 1.07 (3H, s), 1.10 (3H, s), 1.78 (3H, d, J = l.0Hz),

1.83 (3H, s), 2.16-2.26 (1H, m), 2.28 (3H, s),

 2.28 (lH, dd, J = 9.3Hz, 15.6Hz), 2.38 (1H, dd, J = 7.8Hz, 15.6Hz),

 2.93-3.03 (lH, m), 3.63 (1H, t, J = 6.9Hz), 4.16 (1H, d, J = 6.8Hz),

 4.34 (1H, d, J = 8.3Hz), 4.36 (1H, d, J = 8.3Hz), 4.54-4.59 (lH, m),

 4.95 (1H, t, J = 7.8Hz), 5.00 (1H, d, J = 10.7Hz),

34/2

Replacement form (Rule 26) 5.08 (1H, dd, J 1.5 Hz, 17.1Ηζ), 5.10 (1H, d, J = 5.4 Hz), 5.72 (1H, d, J = 9.8 Hz),-

5.84 (1H, d, J = 6.8 Hz), 5.75-5.90 (lH, m), 5.98 (1H, dd, J = 5.4 Hz, 9.8 Hz),

7.48 (2H, t, J = 7.3Hz), 7.59 (1H, t, J = 7.3Hz), 8.14 (2H, d, J-7.3Hz).

Step 2: 10-aryl-10-deacetoxy-4-deacetyl-7-deokin-6,7-didehydro

-1- 0 -dimethylsilyl- 13- 0-triethylsilylpaccatin Π Ι

Dissolve 162 mg of the compound obtained in the above step 1 in tetrahydrofuran 2.Oml, add 336 ml of bis (2-methoxetoxy) aluminum sodium hydride at 0 ° C, and stir for 3.5 hours. Then, 5.0 ml of saturated ethyl potassium tartrate and 5.0 ml of water were added, and the mixture was separated. The aqueous layer was extracted with 10 ml of ethyl acetate. After the organic layers were combined and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel thin-layer chromatography (developing solvent; hexane: ethyl acetate = 10: 3 (v / v)) to obtain 137 mg of the title compound as a colorless amorphous solid. . Ή-NMR (CDCl ₃ / TS) 5 (ppm):

 -0.23 (3H, d, J = 2.4Hz), 0.05 (3H, d, J = 2.9Hz), 0.66-0.86 (6H, m),

0.99 (3H, s), 1.06 (9H, t, J = 8. LHz), 1.09 (3H, s), 1.72 (6H, s),

2.30-2.42 (1H, m), 2.57 (1H, dd, J = 9.8Hz, 15.3Hz),

 2.84 (1H, dd, J = 2.4Hz, 15.3Hz), 2.88-3.02 (lH, m), 3.67 (1H, t, J = 7.1Hz),

3.82 (1H, s), 4.03 (1H, d, J = 5.7Hz), 4.30 (1H, d, J = 7.8Hz),

 4.33 (1H, d, J = 7.8Hz), 4.55-4.65 (1H, m), 4.68 (1H, d, J = 8.8Hz),

 4.85 (1H, d, J = 5.4 Hz), 5.03 (1H, d, J = 10.3 Hz), 5.12 (1H, d, J = 17.1 Hz),

 5.68 (1H, d, J = 9.1 Hz), 5.73 (1H, d, J = 5.7 Hz), 5.74-5.89 (lH, m),

 5.95 (1H, dd, J = 5.4Hz, 9.1Hz), 7.45 (2H, t, J = 7.3Hz), 7.56 (1H, t, J = 7.3Hz), 8 .17 (2H, d, J = 7.3Hz).

Step 3: 10-aryl-4-0- (cyclopropanecarbonyl) -10-deacetoxy-4-decetyl-7-deoxy-6,7-didehydro-1-〇-dimethylsilyl-13-13-0-triethylsilylpaccatin Π 1

 137 mg of the compound obtained in the above step 2 was dissolved in 3.0 ml of tetrahydrofuran, 800 ml of lithium bis (trimethylsilyl) amide (1 M solution in tetrahydrofuran) was added at −20 ° C., and the mixture was stirred for 15 minutes. Add 72.0 ml of carbonyl

3 5 After stirring for 30 minutes, 10 ml of an aqueous saturated sodium bicarbonate solution and 10 ml of ethyl acetate were added to the reaction solution, and the mixture was separated. The organic layers were combined, washed with saturated saline (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel thin-layer chromatography (developing solvent; hexane: ethyl acetate = 5: 1 (v / v)) to obtain 122 mg of the title compound as a colorless amorphous solid. Ή-NMR (CDCl ₃ / TMS) 5 (ppm):

 -0.23 (3H, d, J = 2.9Hz), 0.09 (3H, d, J = 2.4Hz), 0.56-0.74 (6H, m),

0.96-1.30 (4H, m), 1.02 (9H, t, J 7.8Hz), 1.08 (3H, s), 1.13 (3H, s),

1.71-1.82 (lH, m), 1.79 (3H, d, J = l.0Hz), 1.83 (3H, s), 2.14-2.24 (lH, m), 2.34 (1H, dd, J = 7.3Hz, 15.4 Hz), 2.42 (1H, dd, J = 9.3Hz, 15.4Hz),

2.91-3.01 (1H, m), 3.61 (1H, t, J = 6.8Hz), 4.11 (1H, d, J = 6.4Hz),

4.34 (1H, d, J = 7.8Hz), 4.42 (1H, d, J = 7.8Hz), 4.56-4.62 (1H, m),

 4.98 (1H, t, J = 7.8Hz), 4.99 (1H, dd, J = 1.8Hz, 10.2Hz), 5.05 (1H, d, J = 5.4Hz),

5.08 (1H, dd, J = l.8Hz, 17.1Hz), 5.72 (1H, d, J = 9.8Hz), 5.76-6.01 (lH, m),

5.94 (1H, d, J = 6.4Hz), 5.97 (1H, dd, J = 5.4Hz, 9.8Hz), 7.47 (2H, t, J = 7.3Hz), 7.59 (1H, t, J = 7.3Hz) , 8.12 (2H, d, J = 7.3Hz).

Step 4: 10-aryl-4-0- (cyclopropanecarbonyl) -10-deacetoxy-4-decetyl-7-deoxy-6,7-didedropropacatin I II

 Dissolve 122 mg of the compound obtained in the above step 3 in 3.0 ml of pyridine, add 1.0 ml of pyridine hydrofluoride at 0 ° C, and stir at room temperature for 3.5 hours.Then, the reaction solution is stirred with 10 ml of ethyl acetate and 30 ml of ice water. The mixture was poured into a mixture of the above and separated, and the aqueous layer was extracted with 10 ml of ethyl acetate. The organic layers were combined, washed with a saturated aqueous solution of sodium bicarbonate (10 ml), dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified using thin layer chromatography on silica gel (developing solvent; benzene: ethyl acetate = 3: 1 (v / v)) to give 77.2 mg of the title compound as a colorless amorphous solid. Obtained.

_{Ή-NMR (CDC1 3 / TMS} ) (5 (ppm):

 1.00-1.18 (4H, m), 1.08 (3H, s), 1.11 (3H, s), 1.70-1.88 (3H, m),

 1.83 (6H, s), 2.18-2.38 (3H, m), 2.90-3.02 (1H, m), 3.66 (1H, t, J 6.8Hz),

4.28 (lH, d, J = 6.6Hz), 4.33 (1H, d, J = 8.3Hz), 4.46 (1H, d, J = 8.3Hz),

3 6 4.75-4.87 (1H, m), 4.98-5.05 (2H, m), 5.11 (1H, dd, J = l.2Hz, 16.8Hz),

 5.75 (1H, d, J = 9.8Hz), 5.77-5.90 (1H, m), 5.82 (1H, d, J = 6.6Hz),

 6.00 (1H, dd, J = 5.4Hz, 9.8Hz), 7.49 (2H, t, J = 7.3Hz), 7.62 (1H, t, J = 7.3Hz), 8.15 (2H, d, J = 7.3Hz) .

Step 5: 10-aryl-13-◦-[(2R, 3R) -3_ (tert-butoxycarbonylamino) -3- (2-furyl) -3- (triisopropylsilyl) oxypropionyl] -4 -0- (cyclopropanecarbonyl) -10-deacetoxy-4-deacetyl-7-deoxy-6,7-didehydrodovabactin III

 The compound obtained in the above Step 4 and (3R, 4R) -1- (tert-butoxycarbonyl) -4- (2-furyl) -3- (triisopropylsilyl) oxy-2-azetidinone were prepared in Example 1. The reaction was conducted in the same manner as in Step 8, and the title compound was obtained as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 -0.16 (3H, s), 0.03 (3H, s), 0.77 (9H, s), 1.08-1.41 (4H, m), 1.11 (3H, s), 1.25 (3H, s), 1.37 (9H, s) ), 1.71 (3H, d, J = l.0Hz), 1.76 (1H, s), 1.85 (3H, s), 1.91-1.98 (lH, m), 2.16-2.29 (2H, m), 2.56 (1H , dd, J = 9.6Hz, 15.2Hz),

2.94-3.02 (1H, m), 3.66 (1H, t, J = 6.8Hz), 4.21 (1H, d, J = 6.8Hz),

 4.32 (1H, d, J = 8.3Hz), 4.44 (1H, d, J = 8.3Hz), 4.79 (1H, d, J = l.5Hz),

 5.00-5.07 (2H, m), 5.11 (1H, dd, J = 1.2Hz, 16.9Hz), 5.25 (1H, d, J = 9.8Hz), 5.38 (1H, d, J = 9.8Hz), 5.75 (1H, d, J = 9.7Hz), 5.78-5.90 (1H, m),

 5.86 (1H, d, J = 6.8Hz), 6.01 (1H, dd, J = 5.6Hz, 9.7Hz), 6.16 (1H, t, J = 8.5Hz),

6.22 (1H, d, J = 3.2Hz), 6.34 (1H, dd, J = 3.2Hz, 2.0Hz), 7.33 (1H, s),

 7.50 (2H, t, J = 7.3Hz), 7.61 (1H, t, J = 7.3Hz), 8.12 (2H, d, J2 7.3Hz).

Step 6: 10-aryl-13-〇-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-0- ( Cyclopropanecarbonyl) -10-deacetoxy-4-deacetyl-7-deoxy-6,7-didehydropaccatin 111

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 0.94-1.40 (4H, m), 1.13 (3H, s), 1.25 (3H, s), 1.36 (9H, s), 1.57 (3H, s),

3 7 1.79 (1H, s), 1.84 (3H, s), 1.84-1.93 (lH, m), 2.20-2.37 (2H, m),

2.54 (1H, dd, J = 9.5Hz, 15.4Hz), 2.93-3.03 (lH, m), 3.26 (1H, d, J = 5.4Hz), 3.66 (1H, t, J = 7.lHz), 4.19 (1H, d, J = 6.6Hz), 4.30 (1H, d, J = 8.3Hz),

4.43 (1H, d, J = 8.3Hz), 4.73 (1H, d, J = 3.9Hz), 4.98-5.05 (2H, m),

 5.11 (1H, d, J = 16.6Hz), 5.17 (1H, d, J = 10.0Hz), 5.37 (1H, d, J = 10.0Hz),

5.74 (1H, d, J = 9.7Hz), 5.75-5.88 (lH, m), 5.86 (1H, d, J = 6.6Hz),

 6.01 (1H, dd, J = 5.7Hz, 9.7Hz), 6.17 (1H, t, J = 8.6Hz), 6.32 (1H, d, J = 3.4Hz),

6.37 (1H, dd, J = 3.4Hz, 2. OHz), 7.38 (1H, s), 7.51 (2H, t, J = 7.3Hz),

 7.62 (1H, t, J = 7.3Hz), 8.14 (2H, d, J = 7.3Hz).

Step 7: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-0- (cyclopropanecarbonate ) -10-Deacetoxy-4-deacetyl-7-deoxy-6,7-didehydro-10- (2-morpholinoethyl) baccatin III

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 124.0-129.0. C

Ή-NMR (CDC / TMS) 5 (ppm):

 1.00-1.95 (8H, m), 1.11 (3H, s), 1.23 (3H, s), 1.36 (9H, s),

 1.77 (3H, d, J = 1.0 Hz), 1.83 (1H, s), 2.25-2.65 (8H, m), 3.26 (1H, s),

3.68 (4H, t, J = 4.4Hz), 3.81 (1H, t, J = 6.1Hz), 4.20 (1H, d, J = 6.4Hz),

 4.30 (1H, d, J = 8.3Hz), 4.44 (1H, d, J = 8.3Hz), 4.74 (1H, s),

 5.05 (lH, d, J = 5.8Hz), 5.17 (1H, d, J-9.6Hz), 5.37 (1H, d, J = 9.6Hz),

 5.72 (lH, d, J = 9.8Hz), 5.85 (1H, d, J = 6.4Hz), 6.01 (1H, dd, J = 5.8Hz, 9.8Hz), 6.14 (1H, t, J = 8.5Hz) , 6.32 (1H, d, J = 3.1Hz), 6.37 (1H, dd, J = 3.1Hz, 1.8Hz), 7.38 (lH, d, J = 1.8Hz), 7.50 (2H, t, J = 7.3Hz) ), 7.62 (1H, t, J = 7.3Hz),

8.14 (2H, d, J = 7.3Hz).

Example 3

3 8 H

Process 2

Step 1: 10-aryl-13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propioni 10-deacetoxy-6,7-didedropropachatin III

 The compound obtained in Step 7 of Example 1 and (3R, 4R) -1- (tert-butynecarbonyl) -4- (2-furyl) -3- (tert-butyldimethylsilyl) oxy-2-azetidinone The reaction was carried out in the same manner as in Step 8 of Example 1 to give the title compound as a colorless amorphous solid.

Ή-NR (CDC / TS) d (ppm):

 -0.18 (s, 3H), 0.02 (s, 3H), 0.79 (s, 9H), 1.11 (s, 3H), 1.22 (s, 3H), 1.34 (s, 9H), 1.70 (s, 3H), 1.84 (s, 3H), 2.15-2.29 (m, 2H), 2.43 (m, 1H), 2.49 (s, 3H), 2.99 (m, 1H), 3.66 (t, 1H, J = 6.8Hz), 4.21 (d, 1H, J = 6.5Hz),

4.32 (d, 1H, J = 8.5Hz), 4.42 (d, 1H, J = 8.5Hz), 4.71 (s, 1H),

 5.03 (d, 1H, J = 9.9Hz), 5.11 (m, 2H), 5.29 (d, 1H, J = 9.9Hz),

 5.34 (d, 1H, J = 9.9Hz), 5.75 (d, 1H, J = 6.8Hz), 5.83 (m, 2H),

 6.02 (dd, lH, J = 5.6Hz, 9.9Hz), 6.19 (m, 1H), 6.21 (m, 1H), 6.34 (m, 1H),

7.38 (s, lH), 7.50 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz),

8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 918 (MH ⁺ )

Step 2: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tertbutyldimethylsilyl) oxy-3 (2-furyl) propionyl] -10-deacetoxy-6, 7-Didehydro-10- (2-morpholinoethyl) paccatin III

3 9/1

Replacement paper (Kaikai IJ26) The compound obtained in the above Step 1 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) <5 (ppm):

 -0.17 (s, 3H), 0.01 (s, 3H), 0.79 (s, 9H), 1.10 (s, 3H), 1.21 (s, 3H), 1.35 (s, 9H), 1.78 (s, 3H), 1.85 (s, 3H), 2.20 (m, 2H), 2.30-2.58 (m, 8H), 2.50 (s, 3H), 3.69 (m, 4H), 3.79 (dd, 3H, J = 4.9Hz, 7.0Hz ),

4.23 (d, 1H, J = 6.6Hz), 4.33 (d, 1H, J = 8.1Hz), 4.43 (d, 1H, J = 8.1Hz),

 4.72 (s, lH), 5.12 (d, 1H, J = 5.8Hz), 5.28 (d, 1H, J = 10Hz),

 5.35 (d, 1H, J = 9.9Hz), 5.73 (d, 1H, J-9.9Hz), 5.85 (d, 1H, J-6.6Hz),

 6.04 (dd, 1H, J = 5.8Hz, 9.9Hz), 6.17 (m, 1H), 6.22 (m, 1H), 6.35 (m, 1H),

7.38 (s, lH), 7.50 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz),

8.15 (d, 2H, J = 7.5Hz).

 MS-FAB: 991 (MH +)

Step 3: 13-O-[(2R, 3R) -3 (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetoxy-6,7-didehydro -10-(2-morpholinoethyl)

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 9 of Example 1 to give the title compound as a colorless solid.

Melting point: 125-130 ° C

'.Eta. Anonymous _{(CDC1 3 / TMS) 5 (} ppm):

 1.10 (s, 3H), 1.21 (s, 3H), 1.36 (s, 9H), 1.75 (s, 3H), 1.84 (s, 3H),

 2.25 (m, lH), 2.30-2.48 (m, 8H), 2.42 (s, 3H), 2.55 (m, 1H), 3.69 (m, 4H),

3.79 (m, 1H), 4.21 (d, 1H, J = 6.9Hz), 4.32 (d, 1H, J = 8.5Hz),

 4.42 (d, 1H, J = 8.5Hz), 4.70 (m, 1H), 5.12 (d, 1H, J = 5.5Hz),

 5.26 (d, lH, J = 10Hz), 5.33 (d, 1H, J = 9.9Hz), 5.72 (d, 1H, J = 9.9Hz),

 5.83 (d, 1H, J = 6.9Hz), 6.03 (dd, 1H, J = 5.5Hz, 9.9Hz), 6.18 (t, 1H, J = 9Hz),

6.32 (m, lH), 6.38 (m, 1H), 7.41 (s, 1H), 7.50 (t, 2H, J = 7.5Hz),

7.61 (t, 1H, J = 7.5Hz), 8.16 (d, 2H, J = 7.5Hz).

MS-FAB: 877 (MH ⁺ )

4 0 H

Process 2

Step 1: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-methyl-3-phenyl-2- (trimethylsilyl) oxypropionyl] -10-deacetoxy-6 , 7-Didehydro-10- (2-morpholinoethyl) paccatin III

 62 mg of the compound obtained in Step 7 of Example 1 and cis-l- (tert-butoxycarbonyl) -3-methyl-4-phenyl-3- (trimethylsilyl) oxy- obtained in Step 2 of Reference Example 1 47 mg of 2-azetidinone was dissolved in 3 ml of dry tetrahydrofuran, and in -78, 452 ml of sodium bis (trimethylsilyl) amide was added, followed by reaction at the same temperature for 15 minutes. This was post-treated in the same manner as in step 8 of Example 1, and purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 85:15 (v / v)) to give 10-7 lysyl. -13- 0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-methyl-3-phenyl-2- (trimethylsilyl) oxypropionyl] -10-deacetoxy-6, A 46 m mixture of 7-didedropachatin IH and 10-aryl-13-0- (tert-butoxycalponyl) -10-deacetoxy-6,7-didedropraccatin III was obtained. The resulting mixture was reacted in the same manner as in Step 10 of Example 1, worked up, separated and purified by silica gel thin-layer chromatography (developing solvent; hexane: ethyl acetate = 7: 3 (v / v)). 26 mg of the title compound were obtained as a colorless amorphous solid.

Ή-NMR (CDC / TMS) (5 (ppm):

 0.10 (s, 9H), 1.10 (s, 3H), 1.19 (s, 9H), 1.30 (s, 3H), 1.39 (s, 3H),

 1.76 (s, 3H), 1.88 (s, 3H), 2.10 (m, 1H), 2.30-2.45 (m, 8H), 2.56 (m, 1H),

2.70 (s, 3H), 3.69 (m, 4H), 3.78 (m, 1H), 4.19 (d, 1H, J = 6.7Hz),

 4.38 (d, 1H, J = 8.5Hz), 4.44 (d, 1H, J = 8.5Hz), 4.99 (d, 1H, J = 10Hz),

 5.13 (d, 1H, J = 5.6Hz), 5.50 (d, 1H, J = 9.9Hz), 5.75 (d, 1H, J = 9.9Hz),

 5.85 (d, 1H, J = 6.7Hz), 6.03 (dd, 1H, J = 5.7Hz, 10.0Hz), 6.32 (t, 1H, J = 9Hz),

4 1/1

Replacement form (Rule 26) 7.27-7.38 (m, 5H), 7.52 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz), 8.19 (d, 2H, J = 7.5Hz).

MS-FAB: 973 (MH ⁺ )

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-6, 7-didehydro-10- (2-mol holinoethyl)

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 to give the title compound as a colorless solid.

Melting point: 165-170 ° C

Ή-NR (CDCh / TMS) 5 (ppm):

 1.11 (s, 3H), 1.23 (s, 9H), 1.28 (s, 3H), 1.36 (s, 3H), 1.86 (s, 3H),

 2.20 (m, 1H), 2.35 (m, 4H), 2.44 (m, 4H), 2.57 (m, 1H), 2.65 (s, 3H),

 3.69 (m, 4H), 3.79 (t, 1H, J = 5.5Hz), 4.20 (d, 1H, J = 6.6Hz),

 4.35 (d, 1H, J = 8.2Hz), 4.44 (d, 1H, J = 8.2Hz), 5.03 (d, 1H, J = 10.2Hz),

5.11 (d, 1H, J = 5.6Hz), 5.51 (d, 1H, J = 10.2Hz), 5.72 (d, 1H, J = 9.9Hz),

 5.85 (d, 1H, J = 7.7Hz), 6.03 (dd, 1H, J = 5.6Hz, 10.0Hz), 6.30 (m, 1H),

7.30-7.40 (m, 5H), 7.51 (t, 2H, J = 7.5Hz), 7.61 (t, 1H, J = 7.5Hz),

 8.18 (d, 2H, J = 7.5Hz).

MS-FAB: 901 (Η ')

4 2 0 OTES 0 OTES Step 1 Step 2

Η0 \, TESO, 0

 Mi,

 HO OBz OAc

0 OTBS HO OBz OAc HO OBz OAc

Step 1: 10-aryl-7,13-O-bis (triethylsilyl) -10-deacetoxybaccatin III

 10-Aryl-10-deacetoxy-7-0-triethylsilylbaccatin III was reacted in the same manner as in Step 3 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 0.49-0.71 (m, 12H), 0.94-1.03 (m, 18H), 1.12 (s, 3H), 1.14 (s, 3H),

1.62 (s, 3H), 1.87 (s, 3H), 1.84-1.91 (m, 1H), 2.05-2.11 (m, 1H),

 2.20-2.56 (m, 1H), 2.29 (s, 3H), 2.42-2.50 (m, 2H), 2.78-2.82 (m, 1H),

3.87 (dd, 1H, J = 4.5Hz, 10Hz), 3.97 (d, 1H, J = 7Hz), 4.16 (d, 1H, J = 8Hz),

4.29 (d, 1H, J = 8Hz), 4.53 (dd, 1H, J = 7Hz, 10Hz), 4.90-5.10 (m, 4H),

5.61 (d, 1H, J = 7Hz), 5.71-5.82 (m, 1H), 7.46 (t, 2H, J = 8Hz),

 7.59 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 2: 10-aryl-10-deacetoxy-13-0-triethylsilylpaccatin III 209 mg of the compound obtained in the above step 1 was dissolved in 21 ml of methanol, and 5 mg of p-toluenesulfonic acid was added thereto.晚 Stirred. 2 mg of P-toluenesulfonic acid was further added.

4 3/2

Replacement form (Rule 26) After stirring for 4 hours, 0.1 mL of triethylamine was added, and the reaction solution was concentrated. The obtained residue was purified by silica gel thin-phase chromatography (developing solvent; ethyl acetate: hexane = 1: 2 (v / v)) to give 135 mg of the title compound as a colorless amorphous solid. _{Ή-NMR (CDC1 3 / TMS} ) (5 (ppm):

 0.61-0.72 (m, 6H), 1.01 (t, 9H, J = 7Hz), 1.10 (s, 3H), 1.13 (s, 3H),

1.63 (s, 3H), 1.87 (s, 3H), 1.75-1.84 (m, 1H), 2.06-2.12 (m, 1H),

 2.22-2.34 (m, 2H), 2.28 (s, 3H), 2.53-2.61 (m, 1H), 2.90-2.97 (m, 1H),

3.89 (t, 1H, J = 7Hz), 4.02 (d, 1H, J = 7Hz), 4.19 (d, 1H, J = 8Hz),

 4.30 (d, 1H, J = 8Hz), 4.33-4.36 (m, 1H), 4.90 (t, 1H, J = 8Hz),

 4.98-5.02 (m, 2H), 5.10 (d, 1H, J = 17Hz), 5.63 (d, 1H, J = 7Hz),

 5.75-5.84 (m, 1H), 7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz),

8.10 (d, 2H, J = 8Hz).

Process 3: 10-aryl-10-deoxy-7-hydroxy-7-fluoro-13-0-triethylsilylpaccatin I I I

188 mg of the compound obtained in the above step 2 was dissolved in 10 ml of dichloromethane and cooled to -78. Then, 0.025 ml of getylamino sulfur trifluoride was added, and the mixture was stirred at the same temperature for 15 minutes and at 0 ° C for 30 minutes. The reaction solution was cooled again to −78 ° C., and 0.035 ml of acetylaminosulfur trifluoride was added, followed by stirring at the same temperature for 15 minutes and at 0 ° C. for 40 minutes. After adding a saturated aqueous solution of sodium bicarbonate to the reaction solution and stirring for 10 minutes, the dichloromethane layer was washed with water and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-layer chromatography (developing solvent; ethyl acetate: hexane = 1: 4 (v / v)) to obtain 94 mg of the title compound as a colorless amorphous solid. '' H-paint R (CDCl _{; t} / TMS) (5 (ppm):

 0.59-0.74 (m, 6H), 1.01 (t, 9H, J = 7Hz), 1.03 (s, 3H), 1.07 (s, 3H),

1.66 (s, 3H), 1.83 (s, 3H), 2.07-2.37 (m, 4H), 2.30 (s, 3H),

2.50-2.62 (m, 1H), 2.99-3.07 (m, 1H), 4.11 (dd, 1H, J = 5.5Hz, 8Hz),

4.18 (d, 1H, J = 7Hz), 4.34 (AB type d, each 1H, J two 8Hz),

 4.53 (dd, 1H, J = 3.5Hz, 47Hz), 4.90 (t, 1H, J = 8Hz), 4.99 (d, 1H, J = 10Hz),

5.05 (s, 1H), 5.08 (dd, 1H, J = l. 5Hz, 17Hz), 5.69 (d, 1H, J = 7Hz),

4 4 5.73-5.84 (m, 1H), 7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz),

8.12 (d, 2H, J = 8Hz).

Step 4: 10-aryl-10-deacetoxy-7-deoxy-7-α-fluoropaccatin III The compound obtained in the above Step 3 is reacted in the same manner as in Step 7 of Example 1 to give the title compound Obtained as an amorphous solid.

Melting point: 236-238. C

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 1.07 (s, 6H), 1.67 (s, 3H), 1.87 (s, 3H), 2.18-2.39 (m, 4H), 2.30 (s, 3H),

2.50-2.63 (m, lH), 2.99-3.06 (m, 1H), 4.12 (dd, 1H, J = 5.5Hz, 8Hz),

 4.30 (d, 1H, J = 7Hz), 4.35 (s, 2H), 4.53 (dd, 1H, J = 3Hz, 47Hz), 4.83 (br, 1H),

4.99-5.11 (m, 3H), 5.70 (d, 1H, J = 7Hz), 5.745.85 (m, 1H),

 7.49 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz).

 IR (KBr): 3824, 3548, 3448, 3072, 2984, 2952, 1974, 1910, 1732, 1712,

1690, 1642, 1602, 1584 cm— '

MS-FAB: 571 (MH ⁺ )

Step 5: 10-Aryl-13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10-Deacetoxy-7-Doxy-7-a-Fluoropachatin III

 The compound obtained in the above step 4 and (3R, 4R) -1-(tert-butyn phenyl) -3- (tert-butyldimethylsilyl) oxy-4- (2-furyl) -2- The azetidinone was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

'.Eta. solid _{R (CDC1 3 / TS) 5} (ppm):

 -0.18 (s, 3H), -0.02 (s, 3H), 0.77 (s, 9H), 1.09 (s, 3H), 1.19 (s, 3H), 1.32 (s, 9H), 1.67 (s, 3H) , 1.71 (s, 3H), 2.12-2.28 (m, 3H), 2.47 (s, 3H), 2.48-2.52 (m, 2H), 2.99-3.05 (m, 1H), 4.06-4.11 (m, 1H) ,

4.21 (d, 1H, J = 7Hz), 4.35 (s, 2H), 4.53 (dd, 1H, J = 3Hz, 47Hz),

4.71 (d, 1H, J = 1.5Hz), 4.99-5.10 (m, 3H), 5.26 (d, 1H, J = 10Hz),

 5.36 (d, 1H, J = 10Hz), 5.73 (d, 1H, J = 7Hz), 5.75-5.82 (m, 1H),

 6.19 (t, 1H, J = 8Hz), 6.21 (d, 1H, J = 3Hz), 6.33 (dd, 1H, J = 1.5Hz, 3Hz),

4 5 7.36 (s, 1H), 7.48 (t, 2H, J = 8Hz), 7.57 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz). Process 6: 13-0-[(2R , 3R)-3- (tert-Butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10-deacetoxy-7-dequine-7-α- Fluoro-10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDC / TMS) (5 (ppm):

 -0.18 (s, 3H), -0.01 (s, 3H), 0.78 (s, 9H), 1.08 (s, 3H), 1.18 (s, 3H), 1.34 (s, 9H), 1.68 (s, 3H) , 1.83 (s, 3H), 2.16-2.62 (πι, 12H), 2.48 (s, 3H),

3.64-3.72 (m, 4H), 4.21-4.23 (m, 2H), 4.36 (AB type d, each 1H, J = 8Hz),

4.53 (dd, 1H, J = 3Hz, 47Hz), 4.73 (d, 1H, J = l.5Hz), 5.04 (dd, 1H, J = 2Hz, 9Hz),

5.27 (d, 1H, J = 10Hz), 5.37 (d, 1H, J = 10Hz), 5.75 (d, 1H, J = 7Hz),

 6.18 (t, 1H, J = 8Hz), 6.22 (d, 1H, J = 3Hz), 6.34 (dd, 1H, J = 2Hz, 3Hz),

7.37 (d, 1H, J = lHz), 7.49 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz),

8.13 (d, 2H, J = 8Hz).

Step 7: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetoxy-7-deoxy-7 -α-Fluoro-10- (2-morpholinoethyl)

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 127-133 ° C

Ή-NMR (CDCh / TMS) (5 (ppm):

 1.09 (s, 3H), 1.20 (s, 3H), 1.35 (s, 9H), 1.68 (s, 3H), 1.82 (s, 3H),

 2.37 (s, 3H), 2.17-2.65 (m, 12H), 3.66-3.71 (m, 4H), 4.21-4.25 (m, 2H), 4.35 (AB type d, each 1H, J = 8Hz), 4.53 ( dd, 1H, J = 3Hz, 47Hz),

 4.70 (d, 1H, J = 2Hz), 5.03 (dd, 1H, J = 2Hz, 9Hz), 5.26 (d, 1H, J = 10Hz),

 5.37 (d, 1H, J: 10 Hz), 5.75 (d, 1H, J = 7 Hz), 6.19 (t, 1H, J = 8 Hz),

 6.32 (d, 1H, J = 3Hz), 6.37 (dd, 1H, J = 2Hz, 3Hz), 7.41 (d, 1H, J = 2Hz),

 7.51 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.15 (d, 2H, J = 8Hz).

4 6

: U26

Process 7

47/2 Replacement Paper (Rule 26) Step 1: 4, 10-bis (deacetyl) -10-O- (methylthio) thiocarbonyl-4-0-propionyl-7-0-triethylsilylbaccatin III

 3.00 g of 4,10-bis (deacetyl) -4-0-propionyl-7-0-triethylsilylbaccatin III was dissolved in 24 ml of tetrahydrofuran and cooled to -55 ° C. Then, n-butyllithium (1.69 M hexane solution, 3.44 ml) was added dropwise, and after 10 minutes, 0.34 ml of carbon disulfide and 0.34 ml of methyl iodide were added-at 55 ° C for 1 hour and at 0 ° C. Stir for 1 hour. The reaction solution was poured into a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed with water and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was recrystallized from ethyl acetate and n-hexane to obtain 3.07 g of the title compound as pale yellow crystals.

Melting point: 206-209 ° C

47/3

Replacement form (Rule 26) Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 0.55-0.61 (m, 6H), 0.92 (t, 9H, J = 7Hz), 1.06 (s, 3H), 1.23-1.27 (m, 6H),

1.71 (s, 3H), 1.88-1.92 (m, 1H), 2.26-2.28 (m, 2H), 2.29 (s, 3H),

 2.53-2.64 (m, 3H), 2.65 (s, 3H), 3.87 (d, 1H, J = 7Hz), 4.16 (d, 1H, J = 8Hz),

4.31 (d, 1H, J = 8Hz), 4.53 (dd, 1H, J = 7Hz, 10Hz), 4.84 (br, 1H),

 4.92 (d, 1H, J = 8Hz), 5.67 (d, 1H, J = 7Hz), 7.26 (s, 1H), 7.47 (t, 2H, J = 8Hz),

7.61 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz).

 IR (Br): 3884, 3480, 3068, 2948, 2880, 2744, 2424, 2272, 1912, 1716,

1602 cm— ¹

MS-FAB: 763 (MH ⁺ )

Step 2: 10-Deacetoxy-4-deacetyl-10- (2-formylethyl) -4-0-propionyl-7-0-triethylsilylpaccatin III

 1.50 g of the compound obtained in the above step 1, 1.42 ml of acrolein, tris (trimethylsilyl) silane hydride and 2 ′, 2′-azobis (isobutyronitrile) 63 were added to 22.5 ml of benzene, and the mixture was stirred under nitrogen at 130 The mixture was heated under reflux at ° C for 5 hours (twice on the same scale). After allowing the reaction mixture to cool, the residue obtained by concentration under reduced pressure was purified by silica gel gel chromatography (elution solvent: ethyl acetate: hexane = 1: 2 (v / v)). 1.64 g of the product were obtained as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 0.52-0.64 (m, 6H), 0.96 (t, 9H, J = 7Hz), 1.05 (s, 3H), 1.12 (s, 3H),

1.24 (t, 3H, J = 7Hz), 1.63 (s, 3H), 1.94 (s, 3H), 1.85-2.67 (m, 10H),

3.81-3.84 (m, lH), 4.01 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz),

4.30 (d, 1H, J = 8Hz), 4.55 (dd, 1H, J = 7Hz, 10Hz), 4.84 (br, 1H),

4.92 (d, 1H, J = 8Hz), 5.60 (d, 1H, J = 7Hz), 7.46 (t, 2H, J-8Hz),

7.60 (t, 1H, J = 8H2), 8.11 (d, 2H, J = 8Hz), 9.80 (s, 1H).

Step 3: 10-Deacetoxy-4-deacetyl-10- (3-hydroxypropyl) -4-0-propionyl-7-0-Triethylsilylbaccatin III

 1.90 g of the compound obtained in the above step 2 was dissolved in 38 ml of tetrahydrofuran, 295 m of sodium borohydride was added under ice cooling, and the mixture was stirred for 50 minutes. Acid with 1N aqueous hydrochloric acid

4 8 And extracted twice with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium bicarbonate and a saturated saline solution in that order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography on silica gel (eluent; solvent: chloroform: methanol = 50: 1 to 20: 1 (v / v)) to give 1.63 g of the title compound as a colorless amorphous solid . Ή-NMR (CDCh / TS) (5 (ppm):

 0.49-0.63 (m, 6H), 0.95 (t, 9H, J = 7Hz), 1.05 (s, 3H), 1.11 (s, 3H),

1.24 (t, 3H, J = 7Hz), 1.63 (s, 3H), 1.97 (s, 3H), 1.70-2.68 (m, 10H),

 3.64-3.71 (m, 1H), 3.83 (dd, 1H, J = 3.5Hz, 9Hz), 4.06 (d, 1H, J = 7Hz),

4.17 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.55 (dd, 1H, J = 7Hz, 10Hz),

4.84 (br, lH), 4.92 (dd, 1H, J = 2Hz, 9Hz), 5.60 (d, 1H, J = 7Hz),

 7.46 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz),

9.80 (s, 1H).

Step 4: 10-Deacetoxy-4-deacetyl-10- [3- (2-ditropenylzeleno) propyl] -4- 4- 0-propionyl-7- 0-triethylsilyl paccatin 111

 1.63 g of the compound obtained in the above step 3 was dissolved in 33 ml of tetrahydrofuran, and 631 mg of 2-ditrophenylenylenosinate was added at room temperature and stirred for 1 hour. After concentration, the resulting residue was purified by silica gel gel chromatography (elution solvent: ethyl acetate: hexane = 1: 2 (v / v)) to obtain 1.31 g of the title compound as a yellow amorphous solid. Obtained.

 Ή-NMR (CDCh / TMS) 5 (ppm):

 0.48-0.61 (m, 6H), 0.93 (t, 9H, J = 7Hz), 1.03 (s, 3H), 1.12 (s, 3H),

1.24 (t, 3H, J = 7Hz), 1.63 (s, 3H), 1.94 (s, 3H), 1.75-2.67 (m, 10H),

2.89-3.05 (m, 2H), 3.83 (dd, 1H, J = 3.5Hz, 9Hz), 4.03 (d, 1H, J = 7Hz),

4.16 (d, 1H, J2 8Hz), 4.30 (d, 1H, J = 8Hz), 4.55 (dd, 1H, J = 7Hz, 10Hz),

 4.82 (br, 1H), 4.91 (d, 1H, J = 8Hz), 5.59 (d, 1H, J = 7Hz), 7.30-7.35 (m, 1H), 7.46 (t, 2H, J2 8Hz), 7.52 (d, 1H, J = 4Hz), 7.60 (t, 1H, J = 8Hz),

 8.12 (d, 2H, J = 8Hz), 8.29 (d, 1H, J = 8Hz).

Step 5: 10-aryl-10-deacetoxy-4-deacetyl-4-0-propionyl-7-0-triethylsilyl baccatin III

4 9 1.15 g of the compound obtained in the above step 4 was dissolved in 20 ml of tetrahydrofuran, and under ice-cooling, 243 mg of metabenzo-perbenzoic acid was added, and the mixture was returned to room temperature and stirred for 1 hour. An aqueous solution of saturated sodium bicarbonate was added, extracted with ethyl acetate, and washed with saturated saline. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent; solvent: acetone: 50: 1 (v / v)) to obtain 615 mg of the title compound as a pale yellow amorphous solid.

Ή-NMR (CDCl ₃ / TS) <5 (ppm):

 0.50-0,64 (m, 6H), 0,96 (t, 9H, J = 7Hz), 1.07 (s, 3H), 1.13 (s, 3H),

1.24 (t, 3H, J = 7Hz), 1.63 (s, 3H), 1.92 (s, 3H), 1.75-1.87 (m, 1H),

 2.20-2.30 (m, 2H), 2.45-2.70 (m, 4H), 2.76-2.83 (m, 1H),

 3.90 (dd, 1H, J = 4.5Hz, 10Hz), 4.05 (d, 1H, J = 7Hz), 4.18 (d, 1H, J = 8Hz),

 4.30 (d, 1H, J = 8Hz), 4.55 (dd, 1H, J = 7Hz, 10Hz), 4.83 (br, 1H),

4.92 (d, 1H, J = 8Hz), 5.02 (d, 1H, J = 10Hz), 5.09 (d, 1H, J = 17Hz),

 5.60 (d, 1H, J = 7Hz), 5.73-5.84 (m, 1H), 7.46 (t, 2H, J = 8Hz),

7.59 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz).

Process 6: 10-aryl-7,13-0-bis (triethylsilinole) -10-deacetoxy-4-decetyl-4-0-propionylbaccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 3 of Example 1 to obtain the title compound as a colorless amorphous solid.

'H-Tough R (CDC / TS) 5 (ppm):

 0.49-0.70 (m, 12H), 0.94-1.02 (m, 18H), 1.12 (s, 3H), 1.15 (s, 3H),

1.27 (t.3H, J = 7Hz), 1.62 (s, 3H), 1.85 (s, 3H), 1.84-1.91 (m, 1H),

2.02-2.23 (m, 2H), 2.41-2.51 (m, 2H), 2.61 (q, 2H, J = 7Hz),

2.77-2.84 (m, 1H), 3.85 (dd, 1H, J = 4Hz, 10Hz), 3.94 (d, 1H, J = 7Hz),

4.17 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.54 (dd, 1H, J = 7Hz, 10Hz),

4.91-4.94 (m, 2H), 5.01 (d, 1H, J = 10Hz), 5.07 (d, 1H, J = 17Hz),

5.61 (d, 1H, J = 7Hz), 5.71-5.82 (m, 1H), 7.46 (t, 2H, J = 8Hz),

7.59 (t, 1H, J = 8Hz), 8.11 (d, 2H, J = 8Hz).

Step 7: 10-aryl-10-deacetoxy-4 deacetyl-4-0-propionyl-13-0-

5 0 Triethylsilinorebaccatin Π I

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 2 of Example 5 to obtain the title compound as a colorless amorphous solid.

1 H-NMR (CDCh / TMS) (5 (ppm):

 0.61-0.73 (m, 6H), 1.00 (t, 9H, J-7Hz), 1.10 (s, 3H), 1.14 (s, 3H),

 1.26 (t, 3H, J = 7Hz), 1.63 (s, 3H), 1.85 (s, 3H), 1.75-1.84 (m, 1H),

2.04-2.10 (m, 1H), 2.20-2.33 (m, 2H), 2.54-2.70 (m, 3H),

 2.90-2.97 (m, 1H), 3.88 (t, 1H, J = 7Hz), 3.99 (d, 1H, J = 7Hz),

4.20 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz), 4.34-4.40 (m, 1H),

 4.87-5.02 (m, 3H), 5.09 (dd, 1H, J = l.5Hz, 17Hz), 5.64 (d, 1H, J = 7Hz),

 5.75-5.85 (m, 1H), 7.47 (t, 2H, J = 8Hz), 7.62 (t, 1H, J = 8Hz),

8.11 (d, 2H, J = 8Hz).

Step 8: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-fluoro- mouth-4--0-propionyl-13-0-triethylsilyl baccatin III

 The compound obtained in the above Step 7 was reacted in the same manner as in Step 3 of Example 5 to obtain the title compound as a colorless amorphous solid.

'H-Marauder (CDCh / TMS) 5 (ppm):

 0.62-0.73 (m, 6H), 1.00 (t, 9H, J = 7Hz), 1.07 (s, 3H), 1.14 (s, 3H),

 1.27 (t, 311, J = 7Hz), 1.67 (s, 3H), 1.82 (s, 3H), 2.07-2.35 (m, 4H),

2.49-2.70 (m, 3H), 2.98-3.05 (m, 1H), 4.10 (dd, 1H, J = 5.5Hz, 8Hz),

4.14 (d, 1H, J = 7Hz), 4.34 (AB type d, each 1H, J = 8Hz),

 4.54 (dd, 1H, J = 3.5Hz, 47Hz), 4.91 (t, 1H, J: 8Hz), 4.98-5.09 (m, 3H),

 5.70 (d, 1H, J = 7Hz), 5.72-5.81 (m, 1H), 7.48 (t, 2H, J = 8Hz),

7.61 (t, 1H, J = 8Hz), 8.13 (d, 2H, J 8Hz).

Step 9: 10-aryl-10-deacetoxy-4-decetyl-7-deoxy-7-fluoro-4-4-〇-propionylbaccatin III

 The compound obtained in the above Step 8 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

'Eta - Tsuyoshi _{R (CDC1 3 / TMS) 5} (ppm):

5 1 1.07 (s, 6H), 1.21 (t, 3H, J = 7Hz), 1.67 (s, 3H), 1.87 (s, 3H),

2.16-2.38 (m, 4H), 2.51-2.73 (m, 3H), 2.97-3.06 (m, 1H),

4.13 (dd, 1H, J = 5.5Hz, 8Hz), 4.30 (d, 1H, J = 7Hz), 4.35 (s, 2H),

 4.54 (dd, 1H, J = 3.5Hz, 47Hz), 4.81 (br, 1H), 4.99-5.11 (m, 3H),

 5.70 (d, 1H, J = 7Hz), 5.74-5.89 (m, 1H), 7.48 (t, 2H, J = 8Hz),

7.61 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz).

Step 10: 10-Aaryl-13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10-Deacetoxyl-4-decetyl-7-deoxy-7-α-fluoro-4-0-propionylbaccatin III

 The compound obtained in the above Step 9 and (3R, 4R) -1-(tert-butynecarbonyl) -3- (tert-butyldimethylsilyl) oxy-4- (2-furyl) -2-azetidinone The reaction was carried out in the same manner as in Step 8 of Example 1 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 -0.19 (s, 3H), -0.01 (s, 3H), 0.77 (s, 9H), 1.10 (s, 3H), 1.19 (s, 3H), 1.24 (t, 3H, J = 7Hz), 1.32 ( s, 9H), 1.67 (s, 3H), 1.72 (s, 3H),

2.15-2.28 (m, 3H), 2.48-2.52 (m, 2H), 2.75-2.80 (m, 2H),

 3.00-3.06 (m, 1H), 4.06-4.11 (m, 1H), 4.18 (d, 1H, J = 7Hz),

4.36 (AB type d, each 1H, J = 8Hz), 4.55 (dd, 1H, J = 3.5Hz, 47Hz),

 4.72 (s, lH), 5.00-5.10 (m, 3H), 5.25 (d, 1H, J = 10Hz), 5.32 (d, 1H, J = 10Hz),

5.72-5.83 (m, 2H), 6.15 (t, 1H, J = 8Hz), 6.23 (d, 1H, J = 3Hz),

 6.35 (dd, lH, J = 1.5Hz, 3Hz), 7.38 (s, 1H), 7.48 (t, 2H, J = 8Hz),

 7.58 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz).

Step 11 1: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) _2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10 -Deacetoxy-4- 4-acetyl- 7-deoxy-7- -Fluoro-10 (2-morpholinole)-4-〇-propionyl rubbacatin III

 The compound obtained in the above Step 10 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

5 2 Ή-NMR (CDC / TMS) 5 (ppm):

 -0.18 (s, 3H),-0.01 (s, 3H), 0.78 (s, 9H), 1.08 (s, 3H), 1.19 (s, 3H),

1.23 (t, 3H, J = 7Hz), 1.34 (s, 9H), 1.68 (s, 3H), 1.83 (s, 3H),

 2. 18-2.58 (m, 12H), 2.77-2.79 (m, 2H), 3.66-3.73 (m, 4H),

 4.18-4.23 (m, 2H), 4.36 (AB type d, each 1H, J = 8Hz),

 4.54 (dd, 1H, J = 3.5Hz, 47Hz), 4.73 (s, 1H), 5.02 (d, 1H, J = 8Hz),

 5.26 (d, 1H, J = 10Hz), 5.32 (d, 1H, J = 10Hz), 5.76 (d, 1H, J = 7Hz),

 6.15 (t, 1H, J = 8Hz), 6.24 (d, 1H, J = 3Hz), 6.36 (d, 1H, J = 3Hz), 7.39 (s, 1H),

7.49 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.14 (d, 2H, J = 8Hz).

Step 1 2: 13-0- [(2R, 3R)-3- (tert-butoxycarbonylamino) -3- (2-furyl)-

2-Hydroxypropionyl] -10-deacetoxy-4-deacetyl-7-deokin-7-hi-fluoro-10- (2-morpholinoethyl) -4-0-propionylbaccatin I I I

 The compound obtained in the above Step 11 was reacted in the same manner as in Step 9 of Example 1 to give the title compound as a colorless solid.

Melting point: 130-134 ° C

 Ή-NMR (CDCh / TMS) (5 (ppm):

 1.09 (s, 3H), 1.21 (s, 3H), 1.26 (t, 3H, J = 7Hz), 1.33 (s, 9H), 1.68 (s, 3H), 1 82 (s, 3H), 2.18-2.76 (m, 14H), 3.65-3.69 (m, 4H), 4.18 (d, 1H, J = 7Hz), 4.24 (t, 1H, J = 5.5Hz), 4.36 (AB type d, each 1H, J = 8Hz),

 4.54 (dd, 1H, J = 3.5Hz, 47Hz), 4.70 (d, 1H, J = l.5Hz),

 5.00 (dd, 1H, J = 2Hz, 9Hz), 5.19 (d, 1H, J = 10Hz), 5.33 (d, 1H, J = 10Hz),

 5.75 (d, 1H, J = 7Hz), 6.20 (t, 1H, J = 8Hz), 6.33 (d, 1H, J = 3.5Hz),

 6.38 (dd, 1H, J = 2Hz, 3.5Hz), 7.43 (s, 1H), 7.50 (t, 2H, J = 8Hz),

7.61 (t, 1H, J = 8Hz), 8.16 (d, 2H, J = 8Hz).

 IR (KBr): 3456, 2976, 2812, 1718, 1604, 1494 cm— '

MS-FAB: 911 (MIT)

Example 7

5 3

TBSO /.

 N,

 Process 6 0 Boc BocHN o

 H0, \, Process 7

 0 OTBS

Sun

BocHN o Process 9 BocHN

OTBS HO OBz, 0 0 OH HO OBz 0

Step 1: 10-aryl-7,13-◦-bis (triethylsilyl) -10-deacetoxy-1-0 dimethylsilylpaccatin III

 The compound obtained in Step 1 of Example 5 was reacted in the same manner as in Step 1 of Example 2 to obtain the title compound as colorless crystals.

Melting point: 122 ° C

 Ή-NMR (CDCh / TS) (5 (ppm):

 -0.28 (d, 3H, J = 2.7Hz), 0.06 (d, 3H, J = 2.7Hz), 0.55 (m, 6H), 0.69 (m, 6H), 0.95 (m, 9H), 1.03 (m, 9H), 1.10 (s, 3H), 1.13 (s, 3H), 1.61 (s, 3H),

1.85 (m, lH), 1.87 (s, 3H), 2.27 (m, 1H), 2.29 (s, 3H), 2.30 (m, 1H),

2.44 (m, 2H), 2.81 (m, 1H), 3.83 (dd, 1H, J = 4.0Hz, 10.0Hz),

3.95 (d, 1H, J = 7.3Hz), 4.24 (m, 2H), 4.47-4.55 (m, 2H), 4.94-5.09 (m, 3H), 5.68 (d, 1H, J2 7.3Hz), 5.77 (m, 1H), 7.45 (t, 2H, J = 7.5Hz),

7.57 (t, 1H, J = 7.5Hz), 8.09 (m, 2H).

MS-FAB: 855 (MH ⁺ )

Process 2: 10-aryl-7,13-0-bis (triethylsilyl) -10-deacetoxy-4-de

5 4/2

Replacement form (Rule 26) Cetyl-lo-dimethylsilyl baccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 2 of Example 2 to obtain the title compound as colorless crystals.

Melting point: 158-160. C

 Ή-NMR (CDCh / TMS) 5 (ppm):

 -0.30 (d, 3H, J-2.7Hz), 0.00 (d, 3H, J = 2.7Hz), 0.53 (m, 6H), 0.78 (m, 6H), 0.92 (m, 12H), 1.22 (m, 12H), 1.51 (s, 3H), 1.85 (s, 3H), 1.97 (m, 1H),

2.35 (m, 1H), 2.52 (m, 1H), 2.63 (m, 1H), 2.73 (m, 1H), 2.81 (m, 1H),

3.67 (s, lH), 3.70 (d, 1H, J: 6.0Hz), 3.88 (dd, 1H, J = 5.0Hz, 10.0Hz),

 4.06 (dd, 1H, J = 6.0Hz, 12.OHz), 4.19 (d, 1H, J = 8.3Hz), 4.30 (d, 1H, J = 8.3Hz),

4.55 (m, 1H), 4.66 (m, 2H), 5.03 (m, 2H), 5.55 (d, 1H, J-6.0Hz),

5.77 Cm, 1H), 7.42 (t, 2H, J = 7.5Hz), 7.53 (t, 1H, J = 7.5Hz),

 8.10 (d, 2H, J = 7.5Hz).

MS-FAB: 813 (MH10)

Step 3: 10-aryl-7,13-0-bis (triethylsilyl) -4-〇-cyclopropanecarbonyl-10-deacetoxy-4-deacetyl-1-〇-dimethylsilylpaccatin 1 II The obtained compound was reacted in the same manner as in Step 3 of Example 2 to obtain the title compound as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TMS} ) <5 (ppm):

 -0.28 (d, 3H, J = 2.5Hz), 0.07 (d, 3H, J = 2.5Hz), 0.49-0.72 (m, 12H),

0.94 (t, 9H, J = 7Hz), 1.02 (t, 9H, J = 7Hz), 1.12 (s, 3H), 1.13 (s, 3H),

0.97-1.27 (m, 4H), 1.61 (s, 3H), 1.67-1.89 (m, 2H), 1.87 (d, 3H, J = l.5Hz), 2.28-2.85 (m, 4H), 3.82 (dd , 1H, J = 4. OHz, 10. OHz), 3.95 (d, 1H, J = 7Hz), 4.20 (AB type d, 2H, J = 9Hz), 4.48 (dd, 1H, J = 7Hz, 10Hz) ,

 4.55 (t, 1H, J = 1.5Hz), 4.83 (dd, 1H, J = 2.5Hz, 10Hz), 4.96-5.09 (m, 3H),

5.69 (d, 1H, J2 7Hz), 5.72-5.82 (m, 1H), 7.46 (t, 2H, J = 8Hz),

7.58 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 4: 10-aryl-4- 4-cyclopropanecarbonyl-10-deacetoxy-4-deacetyl-13-〇-triethylsilyl baccatin ΙΠ

5 5 The compound obtained in the above Step 3 was reacted in the same manner as in Step 2 of Example 5 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 0.61-0.71 (m, 6H), 1.00 (t, 9H, J = 7Hz), 1.10 (s, 3H), 1.16 (s, 3H),

0.98-1.27 (m, 4H), 1.63 (s, 3H), 1.69-1.82 (m, 2H), 1.87 (s, 3H),

2.02-2.08 (m, 1H), 2.23-2.33 (m, 2H), 2.49-2.57 (m, 1H),

2.89-2.95 (m, 1H), 3.87 (t, 1H, J = 7Hz), 4.02 (d, 1H, J = 7Hz),

4.19 (d, 1H, J = 8Hz), 4.27 (d, 1H, J = 8Hz), 4.34 (br, 1H),

 4.85 (dd, 1H, J = 2Hz, 9Hz), 4.93 (t, 1H, J = 8Hz), 4.99 (d, 1H, J-2 10Hz),

 5.08 (dd, 1H, J = l.5Hz, 17Hz), 5.64 (d, 1H, J = 7Hz), 5.75-5.85 (m, 1H),

7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 5: 10-Alinole-4-0-cyclopropanecarbonyl-10-deacetoxy-4-deacetyl-7-deoxy-7-α-fluoro-13-0-triethylsilylpaccatin III Compound obtained in Step 4 above Was reacted in the same manner as in Step 3 of Example 5 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 0.62-0.71 (m, 6H), 1.00 (t, 9H, J = 7Hz), 0.98-1,28 (m, 4H), 1.07 (s, 3H), 1.17 (s, 3H), 1.69 (s, 3H ), 1.74-1.81 (m, 1H), 1.83 (s, 3H),

2.03-2.27 (m, 4H), 2.43-2.57 (m, 1H), 2.96-3.06 (m, 1H),

 4.07-4.13 (m, 1H), 4.15 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 9Hz),

 4.45 (d, 1H, J = 9Hz), 4.54 (dd, 1H, J = 3Hz, 47Hz), 4.90 5.09 (m, 4H),

 5.70 (d, 1H, J: 7Hz), 5.75-5.83 (m, 1H), 7.48 (t, 2H, J = 8Hz),

7.61 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz).

Step 6: 10-Arinole-4-0-Cyclopropanecarbonyl-10-Deacetoxy-4-Decetyl-7-Deoxy-7-a-Fluorobaccatin! Π

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDC1., / TMS) 5 (ppm):

 1.00-1.27 (m, 4H), 1.08 (s, 3H), 1.09 (s, 3H), 1.67 (s, 3H),

5 6 1.80-1.85 (m, 1H), 1.87 (s, 3H), 2.12-2.39 (m, 4H), 2.48-2.60 (m, 1H),

2.95-3.06 (m, 1H), 4.10 (dd, 1H, J = 5.5Hz, 8Hz), 4.30 (d, 1H, J = 7Hz),

 4.38 (AB type d, each 1H, J = 9Hz), 4.53 (dd, 1H, J = 3.5Hz, 47Hz),

 4.81 (br, 1H), 4.95-5.11 (m, 3H), 5.72 (d, 1H, J = 7Hz), 5.81-5.85 (m, 1H),

7.49 (t, 2H, J = 8Hz), 7.62 (t, 1H, J = 8Hz), 8.15 (d, 2H, J = 8Hz).

Step 7: 10-aryl-13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilinole) oxy-3- (2-furyl) propionyl ]-4-0-Cyclopropanepancarbonyl-10-deacetoxy-4-deacetinol-7-deoxy-7-H-fluorobaccatin III

 The compound obtained in the above Step 6 and (3R, 4R) -1- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyl) oxy-4- (2furyl) -2-azetidinone were prepared in Examples. The reaction was carried out in the same manner as in Step 8 of 1 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) (5 (ppm):

 -0.20 (s, 3H), -0.03 (s, 3H), 0.74 (s, 9H), 1.07 (s, 3H), 1.18 (s, 3H),

1.04-1.21 (m, 4H), 1.32 (s, 9H), 1.65 (s, 3H), 1.72 (s, 3H),

1.92-1.97 (m, 1H), 2.10-2.27 (m, 3H), 2.44-2.65 (m, 2H),

2.97-3.04 (m, lH), 4.03-4.06 (m, 1H), 4.17 (d, 1H, J = 7Hz),

 4.32 (d, 1H, J = 8Hz), 4.37 (d, 1H, J = 8Hz), 4.51 (dd, 1H, J = 3Hz, 47Hz),

4.77 (d, 1H, J = 2Hz), 4.96-5.00 (m, 2H), 5.06 (dd, 1H, J = l.5Hz, 17Hz),

 5.22 (d, 1H, J = 10Hz), 5.35 (d, 1H, J = 10Hz), 5.72-5.81 (m, 2H),

 6.14 (t, 1H, J = 8Hz), 6.19 (d, 1H, J = 3Hz), 6.31 (dd.1H, J = 1.5Hz, 3Hz),

7.30 (s, 1H), 7.46 (t, 2H, J = 8Hz), 7.55 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz). Step 8: 13-0-[(2R , 3R) -3- (tert-Butkincarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -4-0-cyclopropane force luponyl-10-deacetoxy -4-Decetyl-7-Deoquin-7-Hyfluoro-10- (2-Morpholinoethyl) Nockachin III

 The compound obtained in the above Step 7 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

5 7 -0.16 (s, 3H), 0.02 (s, 3H), 0.78 (s, 9H), 1.09 (s, 3H), 1.21 (s, 3H), -1.08-1.22 (m, 4H), 1.34 (s, 9H), 1.68 (s, 3H), 1.85 (s, 3H),

1.96-2.01 (m, lH), 2.14-2.61 (m, 12H), 3.65-3.69 (m, 4H),

4.20-4.22 (m, 2H), 4.34 (d, 1H, J = 8Hz), 4.40 (d, 1H, J = 8Hz),

 4.52 (dd, 1H, J = 3Hz, 47Hz), 4.80 (d, 1H, J = 1.5Hz), 5.00 (d, 1H, J = 8Hz),

 5.25 (d, 1H, J = 10Hz), 5.38 (d, 1H, J = 10Hz), 5.76 (d, 1H, J = 7Hz),

 6.15 (t, 1H, J = 8Hz), 6.22 (d, 1H, J = 3Hz), 6.34 (dd, 1H, J = 2Hz, 3Hz),

 7.34 (s, 1H), 7.50 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz). Step 9: 13-〇-[(2R , 3R) -3- (tert-Butoxycarbonylamino) -3_ (2-furyl) -2-hydroxypropionyl] -4-0-cyclopropanecarbonyl-10-deacetoxy-4-deacetyl-7-deoxy- 7-α-Fluoro-10- (2-morpholinoethyl) paccatin

III

 The compound obtained in the above Step 8 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 132-137 ° C

Ή-NMR (CDCh / TMS) (5 (ppm):

 0.97-1.24 (m, 4H), 1.10 (s, 3H), 1.22 (s, 3H), 1.35 (s, 9H), 1.68 (s, 3H),

1.83 (s, 3H), 1.91-1.95 (m, 1H), 2.13-2.67 (m, 12H), 3.66-3.71 (m, 4H),

4.19-4.25 (m, 2H), 4.32 (d, 1H, J = 8Hz), 4.40 (d, 1H, J = 8Hz),

 4.53 (dd, 1H, J = 3Hz, 47Hz), 4.75 (d, 1H, J = l.5Hz), 4.98 (d, 1H, J = 8Hz),

 5.18 (d, 1H, J = 10Hz), 5.38 (d, 1H, J = 10Hz), 5.76 (d, 1H, J = 7Hz),

 6.17 (t, 1H, J = 8Hz), 6.32 (d, 1H, J = 3.5Hz), 6.37 (dd, 1H, J = 2Hz, 3Hz),

 7.39 (s, lH), 7.51 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.14 (d, 2H, J = 8Hz).

IR (KBr): 3452, 2976, 2812, 1724, 1624, 1494, 1454 cm— ¹

MS-FAB: 923 (MH ⁺ )

Example 8

5 8 H

Step 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10 -Deacetoxy-7 -Doxy-7- α-Fluoropaccatin III

 The compound obtained in Step 4 of Example 5 was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

1 H-NMR (CDCl./TMS) 5 (ppm):

 -0.37 (s, 3H),-0.10 (s, 3H), 0.72 (s, 9H), 1.11 (s, 3H), 1.23 (s, 3H), 1.31 (s, 9H), 1.69 (s, 3H) , 1.73 (s, 3H), 2.12-2.34 (m, 3H), 2.55 (s, 3H), 2.50-2.65 (m, 2H), 3.00-3.10 (m, 1H), 4.05-4.09 (m, 1H) ,

 4.22 (d, 1H, J = 7Hz), 4.38 (s, 2H), 4.52 (s, 1H), 4.56 (dd, 1H, J = 3Hz, 47Hz),

5.00-5.12 (m, 3H), 5.34 (d, 1H, J = 10Hz), 5.45 (d, 1H, J = 10Hz),

5.75 (d, 1H, J = 7Hz), 5.76-5.85 (m, 1H), 6.30 (t, 1H, J = 8Hz),

 7.30-7.40 (m, 5H), 7.49 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz),

8.13 (d, 2H, J = 8Hz).

Step 2: 13-〇-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-7-deoxy -7- α-Fluoro-10- (2-morpholinoethyl) paccatin III

5 9/1

Replacement form (Rule 26) The compound obtained in the above Step 1 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 -0.35 (s, 3H), -0.11 (s, 3H), 0.74 (s, 9H), 1.09 (s, 3H), 1.23 (s, 3H), 1.31 (s, 9H), 1.69 (s, 3H) , 1.83 (s, 3H), 2.04-2.63 (m, 13H), 2.55 (s, 3H),

3.67 (m, 4H), 4.21-4.23 (m, 2H), 4.35, 4.38 (each d, total 2H, J = 9Hz),

4.52 (s, 1H), 4.54 (dd, 1H, J = 3Hz, 47Hz), 5.06 (d, 1H, J = 7Hz),

 5.35 (d, 1H, J = 10Hz), 5.46 (d, 1H, J = 10Hz), 5.75 (d, 1H, J = 7Hz),

 6.25 (t, 1H, J = 8Hz), 7.28-7.39 (m, 5H), 7.50 (t, 2H, J = 8Hz),

 7.59 (t, 1H, J = 8Hz), 8.14 (d, 2H, J = 8Hz).

Step 3: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-7-deoxy-7-α-fluoro -10- (2-morpholinole) paccatin 111

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 145-149 ° C

Ή-N R (CDCl3 / TMS) 5 (ppm):

 1.09 (s, 3H), 1.21 (s, 3H), 1.33 (s, 9H), 1.68 (s, 3H), 1.77 (s, 3H),

2.40 (s, 3H), 2.14-2.65 (m, 13H), 3.68 (m, 4H), 4.20-4.24 (m, 2H),

4.33, 4.36 (each d, total 2H, J = 9Hz), 4.52 (dd, 1H, J = 3Hz, 47Hz),

4.61 (s, 1H), 5.02 (dd, 1H, J = 2Hz, 9Hz), 5.30 (d, 1H, J = 10Hz),

5.41 (d, 1H, J = 10Hz), 5.74 (d, 1H, J = 7Hz), 6.19 (t, 1H, J = 8Hz),

7.40-7.42 (m, 5H), 7.51 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz),

8.14 (d, 2H, J2 8Hz).

MS-FAB: 907 (MH ⁺ )

6 o

Step 1: 7, 13-O-bis (triethylsilyl) -10-deacetoxy-10- (2-morpholinoethyl) paccatin III

 The compound obtained in Step 1 of Example 5 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

'H-Oki (CDCl ₃ / TMS) 5 (ppm):

 0.49-0.72 (m, 12H), 0.94-1.03 (m, 18H), 1.11 (s, 3H), 1.12 (s, 3H),

1.62 (s, 3H), 1.96 (s, 3H), 1.75-2.52 (m, 12H), 2.29 (d, 3H, J = 2Hz),

 3.72 (m, 4H), 3.80-3.82 (m, 1H), 3.97 (d, 1H, J = 7Hz), 4.16 (d, 1H 'J = 8Hz),

4.29 (d, 1H, J = 8Hz), 4.53 (dd, 1H, J = 7Hz, 10Hz), 4.92 (t, 1H, J = 8Hz),

6 1/2

Replacement form (Rule 26) 4.98 (d, 1H, J = 9Hz), 5.60 (d, 1H, J = 7Hz), 7.47 (t, 2H, J 8Hz),-7.59 (t, 1H, J = 8Hz) ), 8.10 (d, 2H, J = 8Hz).

Step 2: 7, 13-◦-Bis (triethylsilyl) -10-deacetoxy-4-deacetyl-1-〇-dimethylsilyl-10- (2-morpholinoethyl) paccatin I I I

 81.5 mg of the compound obtained in the above step 1 was dissolved in 2 ml of N, N-dimethylformamide, and 19 mg of imidazole and 0.031 of dimethylsilane chloride were added, followed by stirring at room temperature for 15 minutes. The reaction solution was poured into ice water, extracted with ethyl acetate, washed with water (twice) and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 2 ml of tetrahydrofuran, and under ice-cooling, 0.13 ml of sodium bis (2-methoxyethoxyquin) aluminum hydride (65% wt, toluene solution) was added dropwise and stirred for 20 minutes. 1 ml of a saturated aqueous potassium tartrate solution was added (stirred for about 5 minutes), extracted with ethyl acetate, washed with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-layer chromatography (developing solvent; ethyl acetate: hexane-1: 3 (v / v)) to obtain 68 mg of the title compound as a colorless amorphous solid.

 Ή-NR (CDC / TMS) (5 (ppm):

 -0.30 (d, 3H, J = 3Hz), 0.01 (d, 3H, J = 3Hz), 0.45-0.60 (m, 6H),

0.71-0.86 (m, 6H), 0.92 (t, 9H, J = 7Hz), 1.09 (m, 15H), 1.50 (s, 3H),

1.95 (s, 3H), 1.84-2.56 (m, 11H), 2.80 (dd, 1H, J = 2.5Hz, 15Hz),

 3.66-3.73 (m, 6H), 3.85-3.88 (m, 1H), 4.10 (dd, 1H, J = 7Hz, 10Hz),

 4.20 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.54-4.57 (m, 1H),

4.66-4.69 (m, 2H), 5.54 (d, 1H, J = 7Hz), 7.47 (t, 2H, J = 8Hz),

7.59 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz).

Step 3: 7,13-〇-bis (triethylsilyl) -10-deacetoxy-4-deacetyl-1-1-〇-dimethylsilyl-4--0-ethoxycarbinole-10- (2-morpholinoethyl) baccatin III

 68 mg of the compound obtained in the above step 2 was dissolved in 2 ml of tetrahydrofuran, and 0.23 ml of lithium bis (trimethylsilyl) amide (1 M solution in tetrahydrofuran) was added under ice-cooling. 0.025 ml was added and stirred for 1 hour.

6 2 The reaction solution was poured into a saturated aqueous solution of sodium bicarbonate, extracted with ethyl acetate, washed with water and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-phase chromatography (developing solvent; ethyl acetate: hexane = 1: 3 (v / v)) to obtain 49.5 mg of the title compound as a colorless amorphous solid.

 Ή-NMR (CDCls / TMS) 5 (ppm):

 -0.30 (d, 3H, J = 3Hz), 0.05 (d, 3H, J = 3Hz), 0.50-0.72 (m, 12H),

 0.95 (t, 9H, J = 7Hz), 1.02 (t, 9H, J = 7Hz), 1.10 (s, 3H), 1.12 (s, 3H),

 1.40 (t, 3H, J = 7Hz), 1.61 (s, 3H), 1.95 (s, 3H), 1.71-2.49 (m, 12H),

 3.70-3.83 (m, 5H), 3.97 (d, 1H, J = 7Hz), 4.14-4.27 (m, 3H),

 4.39-4.55 (m, 3H), 4.92-4.99 (m, 2H), 5.69 (d, 1H, J = 7Hz),

 7.45 (t, 2H, J = 8Hz), 7.56 (t, 1H, J = 8Hz), 8.05 (d, 2H, J = 8Hz).

Step 4: 10-Deacetoxy-4-deacetyl-4-{-ethoxycarbonyl-10- (2-morpholinoethyl) _13-0_triethylsilylpaccatin ΠΙ

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 2 of Example 5 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) 5 (ppm):

 0.62-0.68 (m, 6H), 1.00 (t, 9H, J = 7Hz), 1.07 (s, 3H), 1.14 (s, 3H),

1.42 (t, 3H, J = 7Hz), 1.61 (s, 3H), 1.93 (s, 3H), 1.84-2.78 (m, 12H),

 3.68-3.70 (m, 4H), 3.97-4.00 (m, 2H), 4.11-4.17 (m, 1H),

4.19 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz), 4.40-4.51 (m, 2H),

 4.90 (t, 1H, J = 8Hz), 5.00 (dd, 1H, J = 2Hz, 9Hz), 5.61 (d, 1H, J = 7Hz),

7.47 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz).

Step 5: 10-Deacetoxy-4-deacetyl-4-0-ethoxyquincarbonyl-7-0-methylthiomethyl-10- (2-morpholinoethyl) -13-0-triethylsilylpaccatin III Obtained in Step 4 above 23 mg of the compound was dissolved in 0.5 ml of dimethyl sulfoxide and 0.5 ml of acetic anhydride and stirred at room temperature for 17 hours. A saturated aqueous sodium bicarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water (twice) and saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by thin-layer chromatography on silica gel (developing solvent; black form: methanol = 50: 1 (v / v)) to give the title compound.

6 3 12 m was obtained as a colorless amorphous solid.

 Ή-NMR (CDC / TMS) 5 (ppm):

 0.63-0.69 (m, 6H), 1.00 (t, 9H, J = 7Hz), 1.12 (s, 3H), 1.15 (s, 3H),

 1.41 (t, 3H, J = 7Hz), 1.68 (s, 3H), 2.01 (s, 3H), 2.20 (s, 3H),

1.73-2.77 (m, 12H), 3.69-3.75 (m, 4H), 4.07 (d, 1H, J = 7Hz),

 4.10-4.17 (m, 1H), 4.18 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

4.31-4.36 (m, 1H), 4.40-4.48 (m, 1H), 4.56,

 4.65 (each d, total 2H, J = 12Hz), 4.92-4.98 (m, 2H), 5.63 (d, 1H, J = 7Hz), 7.47 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz).

Step 6: 10-Deacetoxy-4-deacetyl-4-0-ethoxycarbonyl-7-0-methyl-10- (2-morpholinoethyl) -13-0-triethylsilylpaccatin III

 9.0 m of the compound obtained in the above step 5 was dissolved in 2 ml of ethanol, 0.2 g of Raney nickel was added, and the mixture was heated under reflux for 20 minutes. After allowing the reaction solution to cool, insolubles were filtered through celite, and the filtrate was concentrated. The obtained residue was purified by silica gel thin-phase chromatography (developing solvent; chloroform: methanol = 50: 1 (v / v)) to obtain 5.7 mg of the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 0.63-0.69 (m, 6H), 1.01 (t, 9H, J = 7Hz), 1.10 (s, 3H), 1.14 (s, 3H),

 1.42 (t, 3H, J = 7Hz), 1.66 (s, 3H), 2.01 (s, 3H), 1.68-2.74 (m, 12H),

 3.27 (s, 3H), 3.69-3.73 (m, 4H), 3.93 (t, 1H, J = 7Hz),

 4.00 (dd, 1H, J = 6Hz, 10Hz), 4.04 (d, 1H, J = 7Hz), 4.14-4.22 (m, 2H),

4.31 (d, 1H, J = 8Hz), 4.40-4.48 (m, 1H), 4.93 (t, 1H, J = 8Hz),

 5.01 (d, 1H, J = 8Hz), 5.61 (d, 1H, J: 7Hz), 7.47 (t, 2H, J = 8Hz),

7.58 (t, 1H, J2 8Hz), 8.10 (d, 2H, J = 8Hz).

Step 7: 10-Deacetoxy-4-deacetyl-4-0-ethoxycarbonyl-7-0-methyl-10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) (5 (ppm):

6 4 1.04 (s, 3H), 1.10 (s, 3H), 1.40 (t, 3H, J = 7Hz), 1.65 (s, 3H),-

2.09 (d, 3H, J = lHz), 1.73-2.78 (m, 12H), 3.28 (s, 3H), 3.63-3.78 (m, 4H),

3.98-4.02 (m, 2H), 4.11-4.40 (m, 5H), 4.83 (t, 1H, J = 8Hz),

5.06 (d, 1H, J = 8Hz), 5.60 (d, 1H, J = 7Hz), 7.48 (t, 2H, J = 8Hz),

7.59 (t, 1H, J = 8Hz), 8.11 (d, 2H, J = 8Hz).

Step 8: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-thenyl) propionyl] -10- Deacetoxy-4-deacetyl-4-0-ethoxycarbonyl-7-0-methyl-10- (2-morpholinoethyl) baccatin 111

 The compound obtained in the above Step 7 and (3R, 4R) -1- (tert-butoxycarbonyl) -3-((tert-butyldimethylsilyl) oxy-4- (2-chenyl) -2 -Azetidinone was reacted in the same manner as in Step 8 of Example 1 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TS) 5 (ppm):

 -0.15 (s, 3H), 0.02 (s, 3H), 0.83 (s, 9H), 1.14 (s, 3H), 1.20 (s, 3H), 1.33-1.37 (m, 12H), 1.68 (s, 3H) ), 1.94 (s, 3H), 1.75-2.77 (m, 12H),

 3.27 (s, 3H), 3.68 (m, 4H), 3.95-4.03 (m, 2H), 4.08 (d, 1H, J = 7Hz),

4.14 (d, 1H, J = 8Hz), 4.34 (d, 1H, J = 8Hz), 4.36-4.42 (m, 1H),

 4.50-4.58 (m, 2H), 5.02 (d, 1H, J = 8Hz), 5.37 (d, 1H, J = 10Hz),

 5.57 (d, 1H, J = 10Hz), 5.67 (d, 1H, J = 7Hz), 6.15 (t, 1H, J = 8Hz),

7.00-7.04 (m, 2H), 7.22-7.25 (m, 1H), 7.47 (t, 2H, J = 8Hz),

 7.58 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz).

Step 9: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- (2-thenyl) propionyl] -10 deacetoxy-4-decetyl-4 -0-Ethoxycarbonyl-7-0-methyl-10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 8 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 140-145. C

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.14 (s, 3H), 1.17 (s, 3H), 1.32 (t, 3H, J = 7Hz), 1.37 (s, 9H), 1.67 (s, 3H),

6 5 1.90 (s, 3H), 1.75-2.75 (m, 12H), 3.26 (s, 3H), 3.69 (m, 4H),-3.90-4.05 (m, 3H), 4.18-4.24 (m, 2H), 4.35 (d, 1H, J = 8Hz),

 4.40-4.48 (m, 1H), 4.63 (s, 1H), 5.03 (d, 1H, J = 8Hz), 5.36 (d, 1H, J = 10Hz),

5.52 (d, 1H, J = 10Hz), 5.66 (d, 1H, J = 7Hz), 6.10 (t, 1H, J = 8Hz),

7.00 (dd, 1H, J = 3.5Hz, 5Hz), 7.15 (s, 1H), 7.27-7.30 (m, 1H),

7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz).

MS-FAB: 955 (MH ⁺ )

Example 10

6 6

Replacement form (Rule 26)

66/2 Replacement Paper (Rule 26) Step 1: 10-Deacetoxy-10- (2-morpholinoethyl) -13-0-triethylsilylbaccatin 111

 The compound obtained in Step 1 of Example 9 was reacted in the same manner as in Example 5, to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TS) 5 (ppm):

 0.63-0.70 (m, 6H), 1.01 (t, 9H, J = 7Hz), 1.07 (s, 3H), 1.11 (s, 3H),

 1.60 (s, 3H), 1.92 (s, 3H), 2.29 (s, 3H), 1.83-2.78 (m, 12H), 3.69 (m, 4H),

6 6/3

Replacement form (Rule 26) 3.95 (d, 1H, J = 7Hz), 3.98 (d, 1H, J = 8Hz), 4.18 (d, 1H, J = 8Hz),

 4.30 (d, 1H, J = 8Hz), 4.51 (dd, 1H, J = 7Hz, 10Hz), 4.88 (t, 1H, J = 8Hz),

5.04 (d, 1H, J = 8Hz), 5.69 (d, 1H, J-7Hz), 7.47 (t, 2H, J2 8Hz),

 7.60 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 2: 10-Deacetoxy-7-0-methylthiomethyl -10- (2-morpholinoethyl) -13-0-triethylsilylpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 5 of Example 9 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 0.62-0.72 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.12 (s, 3H), 1.13 (s, 3H),

 1.68 (s, 3H), 2.00 (s, 3H), 2.21 (s, 3H), 2.30 (s, 3H), 1.78-2.77 (m, 12H),

3.70-3.72 (m, 4H), 4.04 (d, 1H, J = 7Hz), 4.11-4.14 (m, 1H),

 4.17 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.38 (dd, 1H, J = 7Hz, 10Hz),

 4.55, 4.65 (each d, total 2H, J = 12Hz), 4.93 (t, 1H, J = 8Hz),

4.99 (d, 1H, J = 8Hz), 5.61 (d, 1H, J = 7Hz), 7.47 (t, 2H, J = 8Hz),

7.60 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 3: 10-deacetoxy -7-0-methyl -10- (2-morpholinoethyl) -13-0-triethylsilylpaccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 6 of Example 9 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 0.64-0.74 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.09 (s, 3H), 1.10 (s, 3H),

 1.65 (s, 3H), 2.00 (s, 3H), 2.30 (s, 3H), 1.78-2.75 (m, 12H), 3.26 (s, 3H),

3.68-3.74 (m, 4H), 3.95 (dd, 1H, J = 5.5Hz, 7Hz), 3.99-4.04 (m, 2H),

 4.16 (d, 1H, J 2 8Hz), 4.30 (d, 1H, J = 8Hz), 4.91 (t, 1H, J = 8Hz),

 5.03 (dd, 1H, J = 2Hz, 9Hz), 5.58 (d, 1H, J = 7Hz), 7.47 (t, 2H, J = 8Hz),

7.60 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 4: 10-Deacetoxy-7-0-methyl-10- (2-morpholinoethyl) baccatin III The compound obtained in Step 3 above was reacted in the same manner as in Step 7 of Example 1 to give the title compound.

6 7 Obtained as a colored amorphous solid.

 Ή-N R (CDCh / TMS) (5 (ppm):

 1.06 (s, 3H), 1.10 (s, 3H), 1.66 (s, 3H), 2.06 (s, 3H), 2.30 (s, 3H),

1.72-2.76 (m, 12H), 3.27 (s, 3H), 3.63-3.72 (m, 4H), 3.96-4.04 (m, 2H), 4.08 (d, 1H, J = 7Hz), 4.16 (d, 1H , J = 8Hz), 4.30 (d, 1H, J = 8Hz),

4.83 (t, 1H, J = 8Hz), 5.02 (d, 1H, J = 8Hz), 5.58 (d, 1H, J = 7Hz),

7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz).

Step 5: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-methyl-3-phenyl-2- (trimethylsilyl) oxypropionyl] -10-deacetoxy-7- 0-Methyl-10- (2-morpholinoethyl) paccatin III

 43 mg of the compound obtained in the above step 4 and 49.5 mg of the compound obtained in the step 2 of Reference Example 1 were dissolved in 4 ml of tetrahydrofuran and cooled to -78 ° C (under nitrogen). Then, sodium bis (trimethylsilyl) amide (1 M tetrahydrofuran solution, 0.26 ml) was added dropwise, and the mixture was stirred for 10 minutes. After adding a saturated aqueous solution of sodium bicarbonate to the reaction solution, the temperature was returned to room temperature, ethyl acetate was added for extraction, and the mixture was washed with saturated saline. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was subjected to silica gel thin phase chromatography (developing solvent; black form: methanol = 50: 1 (v / v)). Purification gave 48.5 mg of the title compound as a colorless amorphous solid.

_{Ή-NR (CDC1 3 / TMS} ) (5 (ppm):

 0.08 (s, 9H), 1.12 (s, 3H), 1.16 (s, 9H), 1.25 (s, 3H), 1.38 (s, 3H),

 1.67 (s, 3H), 1.87 (s, 3H), 2.68 (s, 3H), 1.82-2.72 (m, 12H), 3.24 (s, 3H),

3.65 (m, 4H), 3.92-3.99 (m, 3H), 4.19 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz),

4.96-5.01 (m, 2H), 5.47 (d, 1H, J = 10Hz), 5.64 (d, 1H, J = 7Hz),

 6.32 (t, 1H, J2 8Hz), 7.26-7.35 (m, 5H), 7.47 (t, 2H, J = 8Hz),

 7.56 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz).

Step 6: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-7-0 methyl-10 -(2-morpho linoethyl)

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 9 of Example 1 to remove the title compound.

6 8 Obtained as a colored solid.

Melting point: 156-160. C

¹ H-NMR (CDCh / TMS) 5 (ppm):

 1.14 (s, 3H), 1.23 (s, 12H), 1.40 (s, 3H), 1.69 (s, 3H), 1.79 (s, 3H),

2.63 (s, 3H), 1.75-2.75 (m, 12H), 3.25 (s, 3H), 3.68 (m, 4H),

 3.94-4.00 (m, 3H), 4.20 (d, IH, J = 8Hz), 4.32 (d, 1H, J = 8Hz),

 5.00-5.05 (m, 2H), 5.56 (d, IH, J = 10Hz), 5.65 (d, IH, J = 7Hz),

 6.29 (t, 1H, J = 8Hz), 7.31-7.38 (m, 5H), 7.49 (t, 2H, J = 8Hz),

 7.59 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz).

MS-FAB: 933 (MH ⁺ )

Example 1 1

6 9

Replacement paper (Kaikai IJ26)

Step 8 Step 10

Process 12

Step 1: 10-Decetyl-10-O- (2,2,2-trichloroethoxycarbonyl) -13-0-triethylsilylpaccatin III

 10-Decetyl -10- 0_ (2,2,2-trichloroethoxycarbonyl) -7-0-triethylsilyl paccatin I Π 28.5 g and imidazole 5.80 g were added to N, N-dimethylphos.

69/4

Replacement form (Rule 26) The residue was dissolved in lumamide (57 ml), and triethylsilane chloride (14.3 ml) was added thereto. The reaction solution was poured into ice water, extracted twice with ethyl acetate, washed with water (twice) and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in 320 ml of methanol: tetrahydrofuran = 1: 1 (v / v), 963 m of p-toluenesulfonic acid was added, and the mixture was stirred at room temperature for 4 hours. 5 ml of triethylamine was added, and the reaction solution was concentrated. Ethyl acetate and water were added to the obtained residue, and the mixture was separated. The aqueous layer was extracted with ethyl acetate, and the organic layers were combined, washed with water and saturated brine in that order, dried over anhydrous sodium sulfate, and the solvent was removed. The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: ethyl acetate: hexane = 1: 4-1: 1 (v / v)) to obtain 23.5 g of the title compound as a colorless amorphous solid. .

'H -read (CDC1 ₃ / TMS) 5 (ppm):

 0.62-0.73 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.14 (s, 3H), 1.20 (s, 3H),

1.68 (s, 3H), 1.83-1.90 (m, 1H), 2.04 (s, 3H), 2.13-2.28 (m, 2H),

2.29 (s, 3H), 2.52-2.60 (m, 1H), 3.77 (d, 1H, J = 7Hz), 4.16 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz), 4.41 -4.45 (m, 1H), 4.77,

 4.91 (each d, total 2H, J-12Hz), 4.95-4.99 (m, 2H), 5.64 (d, 1H, J = 7Hz), 6.17 (s, 1H), 7.48 (t, 2H, J = 8Hz) , 7.61 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz). Step 2: 10-Decetyl-7-0-methylthiomethyl -10-0- (2,2,2-trichloro mouth Ethoxycarbonyl) -13-0-Triethylsilylpaccatin 111

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 5 of Example 9 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC1:, / T S) (5 (ppm):

 0.65-0.73 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.16 (s, 3H), 1.20 (s, 3H),

 1.76 (s, 3H), 1.81-1.88 (m, 1H), 2.15 (s, 3H), 2.18 (s, 3H),

 2.10-2.28 (m, 2H), 2.30 (s, 3H), 2.78-2.85 (m, 1H), 3.85 (d, 1H, J = 7Hz),

4.15 (d, 1H, J = 8Hz), 4.31-4.36 (m, 2H), 4.65,

 4.71 (each d, total 2H, J = 12Hz), 4.75,

 4.87 (each d, total 2H, J = 12Hz), 4.94-4.99 (m, 2H), 5.65 (d, 1H, J 7Hz), 6.47 (s, lH), 7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

7 0 Step 3: 10-Decetyl -7-0-Methylthiomethyl -13-0-Triethylsilylpackatin m

 Dissolve 14.5 g of the compound obtained in the above step 2 in 217.5 ml of a mixed solvent of methanol: acetic acid: tetrahydrofuran = 1: 1: 1 (v / v / v), add 50 g of zinc dust, and add 60 g at 60 ° C. Stir for 5 minutes. After cooling, the insolubles were removed by filtration, the filtrate was concentrated, and azeotroped with toluene. 1N Hydrochloric acid and ethyl acetate were added to the residue and the mixture was partitioned. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and saturated saline in this order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Then, the obtained residue was recrystallized from ethyl acetate-hexane to give 10.7 g of the title compound as colorless crystals.

'H-NMR (CDCh / TS) (5 (ppm):

 0.63-0.73 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.10 (s, 3H), 1.17 (s, 3H),

 1.80 (s, 3H), 1.76-1.82 (m, 1H), 2.11 (s, 6H), 2.13-2.26 (m, 2H),

 2.30 (s, 3H), 2.62-2.70 (m, 1H), 3.96 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz),

4.24 (d, 1H, J = 2.5Hz), 4.32 (d, 1H, J = 8Hz), 4.35 (dd, 1H, J = 7Hz, 10Hz), 4.51,

4.68 (each d, total 2H, J = 12Hz), 4.96-5.00 (m, 2H), 5.60-5.63 (m, 2H),

7.48 (t, 2H, J = 8Hz), 7.61 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 4: 10-Decetyl-7-0-methyl-13-〇-triethylsilylpaccatin III The compound obtained in Step 3 above was reacted in the same manner as in Step 6 of Example 9 to give the title compound as an amorphous amorphous Obtained as a solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 0.63-0.73 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.09 (s, 3H), 1.16 (s, 3H),

1.76 (s, 3H), 1.73-1.81 (m, 1H), 2.06 (d, 3H, J = lHz), 2.10-2.24 (m, 2H), 2.30 (s, 3H), 2.67-2.75 (m, 1H ), 3.26 (s, 3H), 3.87-3.92 (m, 2H),

4.16 (d, 1H, J = 8Hz), 4.28 (d, 1H, J = 2Hz), 4.31 (d, 1H, J = 8Hz),

4.94-5.02 (m, 2H), 5.18 (d, 1H, J = 2Hz), 5.60 (d, 1H, J = 7Hz),

7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.08 (d, 2H, J = 8Hz).

Step 5: 10-Decetyl-7-0-methyl-10-〇- (methylthio) thiocarbonyl -13-0-Triethylsilylbaccatin III

 The compound obtained in Step 4 above was reacted in the same manner as in Step 1 of Example 6 to elute the title compound.

7 1 Obtained as a yellow amorphous solid.

_{Ή-NMR (CDC1 3 / TMS} ) 5 (ppm):

 0.64-0.71 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.17 (s, 3H), 1.24 (s, 3H),

 1.72 (s, 3H), 1.71-1.78 (m, 1H), 2.15 (d, 3H, J = lHz), 2.13-2.25 (m, 2H),

2.30 (s, 3H), 2.64 (s, 3H), 2.71-2.79 (m, 1H), 3.29 (s, 3H),

 3.85 (d, 1H, J = 7Hz), 3.96 (dd, 1H, J = 7Hz, 10Hz), 4.14 (d, 1H, J = 8Hz),

4.31 (d, 1H, J = 8Hz), 4.96 (t, 1H, J-2 8Hz), 5.00 (d, 1H, J = 8Hz),

 5.66 (d, 1H, J = 7Hz), 7.48 (t, 2H, J = 8Hz), 7.50 (s, 1H), 7.61 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz) .

Step 6: 10-Deacetoxy-10- (2-formylethyl) -7-0-methyl -13-0-triethylsilyl baccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 2 of Example 6 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) 5 (ppm):

 0.60-0.72 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.10 (s, 3H), 1.11 (s, 3H),

 1.64 (s, 3H), 1.70-2.73 (m, 8H), 1.97 (d, 3H, J = lHz), 2.29 (s, 3H),

 3.24 (s, 3H), 3.77-3.80 (m, 1H), 3.95 (d, 1H, J = 7Hz),

 4.00 (dd, 1H, J = 7Hz, 10Hz), 4.16 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz),

4.90 (t, 1H, J = 8Hz), 5.01 (d, 1H, J = 8Hz), 5.58 (d, 1H, J = 7Hz),

 7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.08 (d, 2H, J = 8Hz), 9.80 (s, 1H). Process 7: 10-deacetoxy-10- ( 3-hydroxypropyl) -7-0-methyl-13-0-triethylsilyl baccatin III

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 3 of Example 6 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) <5 (ppm):

 0.62-0.70 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.09 (s, 3H), 1.11 (s, 3H),

 1.65 (s, 3H), 1.50-2.74 (m, 8H), 1.94 (d, 3H, J = lHz), 2.30 (s, 3H),

 3.26 (s, 3H), 3.67-3.73 (m, 3H), 4.00-4.05 (m, 2H), 4.16 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.90 (t , 1H, J = 8Hz), 5.02 (d, 1H, J = 8Hz),

7 2 5.58 (d, 1H, J = 7Hz), 7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz),

8.09 (d, 2H, J = 8Hz).

Step 8: 10-Deacetoxy-7-0-methyl-10- [3- (2-nitrophenylzeleno) propyl] -13-13-Triethylsilylpaccatin III

 The compound obtained in the above Step 7 was reacted in the same manner as in Step 4 of Example 6 to obtain the title compound as a yellow amorphous solid.

 Ή-NMR (CDCh / TS) (5 (ppm):

 0.64-0.70 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.09 (s, 6H), 1.65 (s, 3H),

1.53-3.08 (m, 10H), 1.91 (d, 3H, J = lHz), 2.29 (s, 3H), 3.20 (s, 3H),

3.70 (dd, 1H, J = 5Hz, 7Hz), 3.97 (d, 1H, J = 7Hz), 4.00 (dd, 1H, J = 7Hz, 10Hz), 4.16 (d, 1H, J = 8Hz), 4.30 ( d, 1H, J = 8Hz), 4.89 (t, 1H, J = 8Hz),

5.01 (d, 1H, J = 8Hz), 5.58 (d, 1H, J = 7Hz), 7.41-7.62 (m, 6H),

8.09 (d, 2H, J = 8Hz), 8.28 (d, 1H, J = 8Hz).

Step 9: 10-aryl-10-deacetoxy-7-0-methyl -13-0-triethylsilylbactin III

 The compound obtained in the above Step 8 was reacted in the same manner as in Step 5 of Example 6 to obtain the title compound as a pale yellow amorphous solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 0.62-0.72 (m, 6H), 1.02 (t, 9H, J = 7Hz), 1.11 (s, 3H), 1.12 (s, 3H),

1.65 (s, 3H), 1.71-1.78 (m, 1H), 1.92 (s, 3H), 2.04-2.26 (m, 3H),

 2.29 (s, 3H), 2.65-2.72 (m, 1H), 2.94-3.00 (m, 1H), 3.25 (s, 3H),

 3.80 (t, 1H, J = 7Hz), 3.97-4.01 (m, 2H), 4.16 (d, 1H, J = 8Hz),

 4.30 (d, 1H, J = 8Hz), 4.91 (t, 1H, J = 8Hz), 4.97-5.11 (m, 3H),

 5.59 (d, 1H, J = 7Hz), 5.78-5.89 (m, 1H), 7.47 (t, 2H, J = 8Hz),

7.60 (t, 1H, J 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 10: 10-aryl-10-deacetoxy-7-0-methylbaccatin III

 The compound obtained in the above Step 9 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

7 3 1.06 (s, 3H), 1.11 (s, 3H), 1.66 (s, 3H), 1.73-1.80 (m, 1H), 1.97 (s, 3H),

2.24-2.33 (m, 3H), 2.29 (s, 3H), 2.66-2.74 (m, 1H), 2.94-3.01 (m, 1H),

3.26 (s, 3H), 3.83 (t, 1H, J = 7Hz), 3.99 (dd, 1H, J = 7Hz, 10Hz),

 4.06 (d, 1H, J = 7Hz), 4.17 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz), 4.84 (m, 1H), 4.99-5.12 (m, 3H), 5.59 (d, 1H, J = 7Hz), 5.78-5.89 (m, 1H),

 7.47 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.10 (d, 2H, J = 8Hz).

Step 11 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-methyl-3-phenyl-2- (trimethylsilyl) oxypropionyl] -10- Deacetoxy-7-0-methylbaccatin III

 The compound obtained in the above Step 10 and the compound obtained in Step 2 of Reference Example 1 were reacted in the same manner as in Step 5 of Example 10 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 0.10 (s, 9H), 1.15 (s, 3H), 1.17 (s, 9H), 1.28 (s, 3H), 1.39 (s, 3H),

1.70 (s, 3H), 1.79 (s, 3H), 1.76-1.86 (m, 1H), 2.06-2.10 (m, 1H),

 2.20-2.37 (m, 2H), 2.65-2.71 (m, 1H), 2.70 (s, 3H), 2.97-3.04 (m, 1H),

3.25 (s, 3H), 3.76 (t, 1H, J = 7Hz), 3.93-3.98 (m, 2H), 4.21 (d, 1H, J2 8Hz), 4.31 (d, 1H, J = 8Hz), 4.98 -5.12 (m, 4H), 5,49 (d, 1H, J = 10Hz),

 5.65 (d, 1H, J = 7Hz), 5.80-5.90 (m, 1H), 6.37 (t, 1H, J = 8Hz),

7.25-7.37 (m, 5H), 7.48 (t, 2H, J = 8Hz), 7.56 (t, 1H, J = 8Hz),

8.13 (d, 2H, J2 8Hz).

Step 12: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy -7-0 -Methyl paccatin III

 The compound obtained in the above Step 11 was reacted in the same manner as in Step 9 of Example 1 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 1.16 (s, 3H), 1.23 (s, 9H), 1.26 (s, 3H), 1.37 (s, 3H), 1.69 (s, 3H),

1.72 (s, 3H), 1.76-1.86 (m, 1H), 2.15-2.34 (m, 3H), 2.62 (s, 3H),

2.65-2.73 (m, 1H), 2.94-3.010 (m, 1H), 3.25 (s, 3H), 3.62 (s, 3H),

7 4 3.77 (t, 1H, J = 7Hz), 3.93 (dd, 1H, J = 7Hz, 10Hz), 3.98 (d, 1H, J = 7Hz),

4.21 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz), 4.99-5.11 (m, 4H),

5.55 (d, 1H, J-lOHz), 5.65 (d, 1H, J = 7Hz), 5.76-5.86 (m, 1H),

6.31 (t, 1H, J = 8Hz), 7.32-7.37 (m, 5H), 7.48 (t, 2H, J = 8Hz),

7.58 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 13: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroquinine-2-methyl-3-phenylpropionyl] -10-deacetoxy-7-0- Methyl-10- (2-Mole holinoethyl) paccatin 111

 The compound obtained in the above Step 12 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound (the compound obtained in Step 6 of Example 10) as a colorless solid.

Example 1 2

7 5

Replacement form (Rule 26)

Coming

 75/1

Replacement paper (Kaikai IJ26) Step 1: 13-O-[(2R.3S) -3- (tert-butoxycarbonylamino) -3- (p-fluorophenyl) -2-methyl-2- (trimethylsilyl) oxypropionyl] -10- Deacetoxy-7-0-methyl-10- (2-morpholinoethyl) paccatin III

 The compound obtained in Step 4 of Example 10 and the compound obtained in Step 2 of Reference Example 2 were reacted in the same manner as in Step 5 of Example 10 to obtain the title compound as a colorless amorphous solid. Ή-NMR (CDC / TMS) 5 (ppm):

 0.12 (s, 9H), 1.14 (s, 3H), 1.19 (s, 9H), 1.27 (s, 3H), 1.39 (s, 3H),

1.69 (s, 3H), 1.88 (s, 3H), 2.68 (s, 3H), 1.85-2.75 (m, 12H), 3.26 (s, 3H),

3.68 (m, 4H), 3.95-4.00 (m, 3H), 4.21 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz),

4.97 (d, 1H, J 2 10Hz), 5.02 (d, 1H, J = 8Hz), 5.44 (d, 1H, J = 10Hz),

 5.66 (d, 1H, J = 7Hz), 6.34 (t, 1H, J = 8Hz), 7.05 (t, 2H, J-8Hz),

 7.26 (t, 2H, J = 8Hz), 7.49 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz),

75/2

Replacement form (Rule 26) 8.13 (d, 2H, J = 8Hz).

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -3- (p-fluorophenyl) -2-hydroxy-2-methylpropionyl] -10-deacetoxy-7 -0-Methyl-10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 147-150 ° C

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.14 (s, 3H), 1.22 (s, 9H), 1.23 (s, 3H), 1.38 (s, 3H), 1.68 (s, 3H),

 1.81 (s, 3H), 2.62 (s, 3H), 1.73-2.76 (m, 12H), 3.26 (s, 3H), 3.68 (m, 4H),

3.94-4.01 (m, 3H), 4.20 (d, 1H, J = 8Hz), 4.32 (d, 1H, J = 8Hz),

 4.99-5.04 (m, 2H), 5.49 (d, 1H, J = 10Hz), 5.65 (d, 1H, J = 7Hz),

6.30 (t, 1H, J = 8Hz), 7.06 (t, 2H, J = 8Hz), 7.36 (t, 2H, J = 8Hz),

7.49 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz), 8.13 (d, 2H, J = 8Hz).

MS-FAB: 951 (H ⁺ )

Example 13

7 6

Replacement form (Rule 26)

Process 2

Step 1: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10-deacetoxy-7 -0- Methyl -10_ (2-morpholinoethyl) paccatin III

 Compound obtained in Step 4 of Example 10 and (3R, 4R) -1- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyl) oxy-4- (2-furyl) -2- The azetidinone was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

1 H-NMR (CDC / TMS) 5 (ppm):

 -0.15 (s, 3H), 0.02 (s, 3H), 0.80 (s, 9H), 1.13 (s, 3H), 1.18 (s, 3H),

7 6/2

Replacement form (Rule 26) 1.36 (s, 9H), 1.68 (s, 3H), 1.91 (s, 3H), 2.50 (s, 3H), 1.78-2.77 (m, 12H),

3.27 (s, 3H), 3.68 (m, 4H), 3.93-4.04 (m, 3H), 4.20 (d, 1H, J = 8Hz),

 4.31 (d, 1H, J = 8Hz), 4.74 (s, 1H), 5.01 (d, 1H, J = 9Hz), 5.26 (d, 1H, J = 10Hz), 5.36 (d, 1H, J = 10Hz) , 5.65 (d, 1H, J = 7Hz), 6.19 (t, 1H, J = 8Hz), 6.24 (s, 1H), 6.35 (s, lH), 7.38 (s, 1H), 7.48 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz),

 8.11 (d, 2H, J = 8Hz).

Step 2: 13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- 2-hydroxyquinpropionyl] -10-deacetoxy-7-0-methyl -10- (2-morpholinole) 1 力

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 138-142. C

Ή-NMR (CDCl ₃ / TS) (5 (ppni):

 1.14 (s, 3H), 1.18 (s, 3H), 1.36 (s, 9H), 1.67 (s, 3H), 1.90 (d, 3H, J = lHz), 2.41 (s, 3H), 1.75-2.76 ( m, 12H), 3.26 (s, 3H), 3.68 (m, 4H),

3.95-4.02 (m, 3H), 4.18 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

4.70 (d, 1H, J = 2.5Hz), 4.99 (d, 1H, J = 8Hz), 5.25 (d, 1H, J = 10Hz),

 5.35 (d, 1H, J = 10Hz), 5.64 (d, 1H, J = 7Hz), 6.18 (t, 1H, J = 8Hz),

 6.32 (d, 1H, J = 3.5Hz), 6.38 (dd, 1H, J = 2Hz, 3.5Hz), 7.42 (d, 1H, J = lHz),

7.49 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz), 8.11 (d, 2H, J = 8Hz).

MS-FAB: 909 (MH ⁺ )

Example 14

7 7

Replacement form (Rule 26)

Step 1: 13-0 _ [(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-7-0 -Met

 7 7/1

Replacement paper (Kaikai IJ26) Nore-10- (2-morpholinoethyl) paccatin III

 The compound obtained in Step 4 of Example 10 was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDCh / TMS) 5 (ppm):

 -0.12 (s, 3H), 0.09 (s, 3H), 0.75 (s, 9H), 1.13 (s, 3H), 1.21 (s, 3H), 1.32 (s, 9H), 1.68 (s, 3H), 1.89 (s, 3H), 2.56 (s, 3H), 1.73-2.78 (m, 12H),

3.27 (s, 3H), 3.69 (m, 4H), 3.93-4.04 (m, 3H), 4.20 (d, 1H, J = 8Hz),

 4.32 (d, 1H, J = 8Hz), 4.52 (s, 1H), 5.02 (d, 1H, J = 8Hz), 5.28 (d, 1H, J = 10Hz),

5.43 (d, 1H, J = 10Hz), 5.65 (d, 1H, J = 7Hz), 6.24 (t, 1H, J = 8Hz),

7.27-7.39 (m, 5H), 7.48 (t, 2H, J = 8Hz), 7.59 (t, 1H, J = 8Hz),

 8.11 (d, 2H, J = 8Hz).

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-7-0-methyl-10- ( 2-morpholinole)

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 151-155 ° C

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.14 (s, 3H), 1.19 (s, 3H), 1.35 (s, 9H), 1.67 (s, 3H), 1.85 (d, 3H, J = lHz), 2.37 (s, 3H), 1.73-2.75 ( m, 12H), 3.25 (s, 3H), 3.68 (m, 4H),

 3.93-4.01 (m, 3H), 4.18 (d, 1H, J = 8Hz), 4.30 (d, 1H, J = 8Hz),

 4.61 (s, lH), 4.99 (d, 1H, J = 8Hz), 5.27 (d, 1H, J = 10Hz),

 5.42 (d, 1H, J = 10Hz), 5.63 (d, 1H, J2 7Hz), 6.16 (t, 1H, J = 8Hz),

7.29-7.42 (m, 5H), 7.49 (t, 2H, J = 8Hz), 7.60 (t, 1H, J = 8Hz),

 8.10 (d, 2H, J = 8Hz).

MS-FAB: 919 (H ⁺ )

Example 15

7 8 Process 2

Step 1: 10-aryl-10-deacetoxitol 0-dimethylsilinole-7-0-methyl-13-〇-triethylsilyl paccatin IΠ

 The compound obtained in Step 9 of Example 11 was reacted in the same manner as in Step 1 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDCU / TS) 5 (ppm):

 -0.30 (d, 3H, J = 3Hz), 0.06 (d, 3H, J2 3Hz), 0.62-0.74 (m, 6H),

1.04 (t, 9H, J = 7Hz), 1.08 (s, 3H), 1.11 (s, 3H), 1.65 (s, 3H),

1.71-1.78 (m, 1H), 1.92 (s, 3H), 2.19-2.39 (m, 3H), 2.29 (s, 3H),

2.63 2.70 (m, lH), 2.95-3.01 (m, 1H), 3.24 (s, 3H), 3.77 (t, 1H, J = 7Hz), 3.93-3.98 (m, 2H), 4.24 (s, 2H) , 4.53 (t, 1H, J = 3Hz), 4.92-5.10 (m, 4H), 5.67 (d, 1H, J = 7Hz), 5.79 5.90 (m, 1H), 7.46 (t, 2H, J = 8Hz) ,

7.58 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

Step 2: 10-aryl-10-deacetoxy-4-deacetyl-1-0-dimethylsilyl-7-0-methyl-13-0-triethylsilylbaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 2 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 -0.30 (d, 3H, J = 3Hz), 0.02 (d, 3H, J = 3Hz), 0.76-0.83 (m, 6H), 0.97 (s, 3H), 1.10 (t, 9H, J2 7Hz), 1.12 (s, 3H), 1.55 (s, 3H), 1.76-1.86 (m, 1H),

79/2

Replacement forms (Rule 26) 1.92 (s, 3H), 2.34-2.42 (m, 1H), 2.51-2.64 (m, 2H),

 2.79 (dd, 1H, J = 2.5Hz, 15Hz), 2.93-2.98 (m, 1H), 3.23 (s, 3H),

 3.52 (dd, 1H, J = 5Hz, 12Hz), 3.66 (s, 1H), 3.73 (d, 1H, J = 5.5Hz),

 3.83 (t, 1H, J = 7Hz), 4.21 (d, 1H, J = 8Hz), 4.31 (d, 1H, J = 8Hz),

 4.57 (t, 1H, J = 3Hz), 4.69 (d, 1H, J = 9Hz), 4.74 (dd, 1H, J = 4.5Hz, 10Hz),

 5.00 (d, 1H, J = 8Hz), 5.10 (d, 1H, J = 17Hz), 5.55 (d, 1H, J = 7Hz),

5.76-5.87 (m, 1H), 7.43 (t, 2H, J = 8Hz), 7.55 (t, 1H, J = 8Hz),

 8.12 (d, 2H, J = 8Hz).

Step 3: 10-aryl-10-deacetoxy-4-deacetyl-1-0-dimethylsilinole _4_0-ethoxycarbonyl-7-0-methyl-13-0-triethylsilylpaccatin III The compound obtained in step 2 above Was reacted in the same manner as in Step 3 of Example 9 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 -0.30 (d, 3H, J = 3Hz), 0.06 (d, 3H, J = 3Hz), 0.65-0.73 (m, 6H),

1.03 (t, 9H, J = 7Hz),

 1.11 (s, 6H), 1.41 (t, 3H, J = 7Hz), 1.65 (s, 3H), 1.70-1.80 (m, 1H),

 1.93 (s, 3H), 2.19-2.30 (m, 3H), 2.62-2.70 (m, 1H), 2.94-3.01 (m, 1H),

3.25 (s, 3H), 3.76 (t, 1H, J = 7Hz), 3.93 (dd, 1H, J = 7Hz, lOHz),

 4.00 (d, 1H, J = 7Hz), 4, 10-4.23 (m, 1H), 4.19 (s, 2H), 4.39-4.47 (m, 1H),

4.55 (t, 1H, J = 3Hz), 4.95-5.10 (m, 4H), 5.69 (d, 1H, J = 7Hz),

 5.80-5.91 (m, lH), 7.46 (t, 2H, J = 8Hz), 7.56 (t, 1H, J = 8Hz),

8.10 (d, 2H, J = 8Hz).

Process 4: 10-aryl-10-deacetoxy-4-decetyl-4-0-ethoxycarbonyl-7-7-0-methylbaccatin III

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TS) (5 (ppm):

 1.05 (s, 3H), 1.11 (s, 3H), 1.39 (t, 3H, J = 7Hz), 1.65 (s, 3H),

1.73-1.79 (m, lH), 1.99 (s, 3H), 2.20-2.33 (m, 3H), 2.67-2.74 (m, 1H),

8 0 2.94-3.01 (m, 1H), 3.26 (s, 3H), 3.84 (t, 1H, J = 7Hz),

 3.97 (dd, 1H, J = 7Hz, 10Hz), 4.09 (d, 1H, J = 7Hz), 4.15 (d, 1H, J = 8Hz),

4.16-4.20 (m, 1H), 4.22-4.26 (m, 2H), 4.82 (t, 1H, J = 8Hz),

4.98-5.13 (m, 3H), 5.60 (d, 1H, J = 7Hz), 5.79-5.89 (m, 1H),

 7.47 (t, 2H, J = 8Hz), 7.58 (t, 1H, J = 8Hz), 8.11 (d, 2H, J = 8Hz).

Step 5: 10-aryl-13-0-[(2R, 3S) _3- (tert-butoxycarbonylamino) -2-methyl-3-phenyl-2- (trimethylsilyl) oxypropionyl] -10- Deacetoxy-4-decetyl -4-0-ethoxycarbonyl-7-0-methylbaccatin III

 The compound obtained in Step 4 above and the compound obtained in Step 2 of Reference Example 1 were reacted in the same manner as in Step 5 of Example 10 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) δ (ppm):

 0.06 (s, 9H), 1.15 (s, 3H), 1.25 (s, 3H), 1.26 (s, 9H), 1.41 (t, 3H, J = 7Hz), 1.45 (s, 3H), 1.70 (s, 3H) 3H), 1.84 (s, 3H), 1.81-1.87 (m, 1H),

2.08-2.15 (m, lH), 2.26-2.31 (m, 1H), 2.38-2.44 (m, 1H),

 2.67-2.74 (m, lH), 2.97-3.02 (m, 1H), 3.25 (s, 3H), 3.81 (t, 1H, J = 7Hz),

3.93 (dd, 1H, J = 7Hz, 10Hz), 4.16 (d, 1H, J = 7Hz), 4.30 (s, 2H),

 4.65-4.77 (m, 2H), 5.00-5.16 (m, 4H), 5.53 (d, 1H, J = 10Hz),

 5.67 (d, 1H, J = 7Hz), 5.79-5.90 (m, 1H), 6.30 (t, 1H, J = 8Hz),

7.30-7.45 (m, 7H), 7.56 (t, 1H, J = 8Hz), 8.12 (d, 2H, J = 8Hz).

Step 6: 10-aryl-13-0-[(2R, 3S) -3 (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4- Decetyl -4-〇-ethoxycarbonyl -7-〇-methylbaccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDCU / TS) δ (ppm):

 1.16 (s, 3H), 1.22 (s, 3H), 1.32 (s, 9H), 1.40 (s, 3H), 1.42 (t, 3H, J = 7Hz), 1.69 (s, 3H), 1.74 (s, 3H), 1.78-1.85 (m, 1H), 2.20-2.37 (m, 3H),

 2.66-2.73 (m, lH), 2.94-3.01 (m, 1H), 3.25 (s, 3H), 3.62 (s, 3H),

 3.80 (t, 1H, J = 7Hz), 3.89 (dd, 1H, J = 7Hz, 10Hz), 4.07 (d, 1H, J = 7Hz),

8 1 4.24 (d, 111, J = 8Hz), 4.34 (d, 1H, J = 8Hz), 4.52-4.65 (m, 2H),

 5.00-5.15 (m, 4H), 5.66-5.70 (m, 2H), 5.76-5.86 (m, 1H),

6.21 (t, 1H, J = 8Hz), 7.30-7.46 (m, 7H), 7.58 (t, 1H, J = 8Hz),

8.09 (d, 2H, J = 8Hz).

Step 7: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4-decetyl- 10- (2,3-Dihydroxypropyl) -4-0-ethoxycarbonyl-7-0-methylbaccatin III 98 mg of the compound obtained in the above step 6 was added to tetrahydrofuran: acetone: water = 1: 1: 1 (v / v / v) was dissolved in 12 ml, and N-methylmorpholine-N-oxide 65 mg and osmium tetraoxide 10 mg were added and stirred for 1 hour. The reaction solution was diluted with ethyl acetate, washed with a saturated aqueous solution of sodium sulfite, a saturated aqueous solution of ammonium chloride, and a saturated saline solution in that order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-phase chromatography (developing solvent; black form: methanol = 10: 1 (v / v)) to obtain 81.5 mg of the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TS) (5 (ppm):

 1.11, 1.13 (each s, total 3H), 1.20, 1.21 (each h s, total 3H),

 1.31 (s, 9H), 1.41 (s, 3H), 1.42 (t, 3H, J = 7Hz), 1.69,

 1.70 (each s, total 3H), 1.83, 1.87 (each s, total 3H),

 1.81-2.73 (m, 6H), 3.28, 3.29 (each s, total 3H), 3.46-3.76 (m, 3H),

 3.88-3.95 (m, lH), 4.11-4.18 (m, 2H), 4.24 (d, 1H, J = 8Hz),

 4.34 (d, 1H, J = 8Hz), 4.52-4.65 (m, 2H), 5.04 (d, 1H, J = 9Hz),

 5.14 (d, 1H, J = 10Hz), 5.66-5.68 (m, 2H), 6.19 (m, 1H), 7.32-7.47 (m, 7H), 7.58 (t, 1H, J = 8Hz), 8.09 (d , 2H, J = 8Hz).

Step 8: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4-deacetyl- 4-〇-ethoxycarbonyl-7-0-methyl-10- (2-morpholinoethyl)

 40 mg of the compound obtained in the above step 7 was dissolved in 4 ml of tetrahydrofuran: methanol = 1: 1 (v / v), and 92.5 mg of sodium metaperiodate was dissolved in 2 ml of water under ice-cooling. The solution was added dropwise and stirred at room temperature for 2 hours. After adding water and extracting with ethyl acetate, water,

8 2 The extract was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was dissolved in ethanol (4 ml), acetic acid (0.024 ml) and morpholine (0.037 ml) were added, and sodium borohydride (26 nig) was added, followed by stirring for 15 minutes. A saturated aqueous solution of sodium bicarbonate was added, extracted with ethyl acetate, washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin-phase chromatography (developing solvent; chloroform: methanol = 15: 1 (v / v)), and lyophilized from 1,4-dioxane to give 36.7 mg of the title compound. Was obtained as a colorless solid.

Melting point: 150-152. C

Ή-NMR (CDC / TMS) (5 (ppm):

 1.15 (s, 3H), 1.20 (s, 3H), 1.32 (s, 9H), 1.41-1.44 (m, 6H), 1.69 (s, 3H), 1 82 (s, 3H), 1.80-2.76 (m, 12H), 3.25 (s, 3H), 3.60 (s, 1H),

 3.66-3.68 (m, 4H), 3.91 (dd, 1H, J = 7Hz, 10Hz), 4.00 (t, 1H, J = 6Hz),

 4.09 (d, 1H, J = 7Hz), 4.24 (d, 1H, J = 8Hz), 4.34 (d, 1H, J = 8Hz),

 4.54-4.62 (m, 2H), 5.04 (d, 1H, J = 9Hz), 5.14 (d, 1H, J2 10H2),

 5.60-5.70 (m, 2H), 6.19 (t, 1H, J = 8Hz), 7.29-7.46 (m, 7H),

7.58 (t, 1H, J = 8Hz), 8.09 (d, 2H, J = 8Hz),

MS-FAB: 963 (MH ⁺ )

Example 16

8 3

Replacement form (Rule 26)

83/1 Replacement Paper (Kaikai Ij26) 13-0- [(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroquinine-2-methyl-3-phenylpropionyl] -10-deacetoxy-4-deacetyl-4-0- Ethoxycarbonyl-7-0-methyl-10- [2- (4-methylbiperazinyl) ethyl] paccatin を The compound obtained in Step 7 of Example 15 was treated in the same manner as in Step 8 of Example 15 Reaction using N-methylpiperazine instead of morpholine gave the title compound as a colorless solid.

8 3/2

Replacement form (Rule 26) Melting point: 143-147 ° C

¹ H-NMR (CDCh / TMS) (5 (ppm):

 1.15 (s, 3H), 1.19 (s, 3H), 1.32 (s, 9H), 1.41-1.45 (m, 6H), 1.69 (s, 3H), 1.81 (s, 3H), 1.79-2.72 (m, 16H), 2.27 (s, 3H), 3.26 (s, 3H),

 3.60 (br, IH), 3.90 (dd, IH, J = 7Hz, 10Hz), 4.00 (t, IH, J = 6Hz),

 4.09 (d, IH, J = 7Hz), 4.24 (d, 1H, J = 8Hz), 4.34 (d, IH, J = 8Hz),

4.53-4.60 (m, 2H), 5.04 (d, IH, J = 9Hz), 5.14 (d, IH, J = 10Hz),

5.66 (d, 1H, J = 7Hz), 5.69 (d, 1H, J = 10Hz), 6.18 (t, 1H, J = 8Hz),

7.31-7.46 (m, 7H), 7.58 (t, IH, J = 8Hz), 8.09 (d, 2H, J = 8Hz).

MS-FAB: 976 (MIT)

Example 17

84

Replacement paper (Kaikai IJ26)

84/1 Replacement paper (Kaikai IJ26) 13-O [(2R.3S) -3- (tert-butoxycarbonylamino) -2-hydroquin-2--2-methyl-3-phenylpropionyl] -10-deacetoxy-4-deacetyl-4-0-ethoxyquincarbo Nil -7-0-methyl-10- (2-piperidinoethyl) paccatin III

 The compound obtained in Step 7 of Example 15 was reacted in the same manner as in Step 8 of Example 15 using piperidine instead of morpholine to obtain the title compound as a colorless solid. Melting point: 130-134 ° C

Ή-NMR (CDCh / TS) d (ppm):

 1.14 (s, 3H), 1.20 (s, 3H), 1.32 (s, 9H), 1.68 (s, 3H), 1.80 (s, 3H),

1.41-2.75 (m, 24H), 3.27 (s, 3H), 3.60 (br, 1H), 3.89 (dd, 1H, J = 7Hz, 10Hz), 3.98 (m, 1H), 4.08 (d, 1H, J = 7Hz), 4.24 (d, 1H, J = 8Hz), 4.34 (d, 1H, J = 8Hz), 4.55-4.60 (m, 2H), 5.04 (d, 1H, J = 9Hz), 5.13 (d, 1H, J = 10Hz),

84/2

Replacement form (Rule 26)

Process 3

Process 7

HO OBz OAc

Step 1: 10-aryl-10-deacetoxy-13-〇- (2,2,2-trichloromouth ethoxycarbonyl) baccatin III

 10-aryl-10-deacetoxy-13-0- (2,2,2-trichloroethoxycarbonyl) -7-0-triethylsilylpaccatin III was reacted in the same manner as in Step 1 of Example 1 to give the title compound Was obtained as colorless crystals.

Melting point: 195 ° C

 Ή-NMR (CDCh / TMS) 5 (ppm):

 1.14 (s, 6H), 1.63 (s, 3H), 1.82 (m, 1H), 1.87 (s, 3H), 2.35-2.40 (m, 4H),

2.38 (s, 3H), 2.59 (m, 1H), 2.95 (m, 1H), 3.94 (t, 1H, J = 8Hz),

 4.10 (d, 1H, J = 7.0Hz), 4.18 (d, 1H, J = 8.0Hz), 4.32 (d, 1H, J = 8.0Hz),

 4.39 (m, 1H), 4.35 (AB type d, 2H, J = 12Hz), 4.96 (d, 1H, J = 8.0Hz),

 5.02 (d, 1H, J = 9.9Hz), 5.13 (d, 1H, J = 17Hz), 5.68 (d, 1H, J = 7.0Hz),

 5.78 (m, lH), 5.94 (m, 1H), 7.49 (t, 2H, J = 7.5Hz), 7.62 (t, 1H, J = 7.5Hz), 8.09 (d, 2H, J = 7.5Hz).

MS-FAB: 744 (MH ⁺ )

8 5/2

Replacement paper (Kaikai IJ26) IR (KBr): 3484, 3160, 3070, 2956, 2902, 2452, 2260, 1969, 1764, 1731, 1713, 1644 cm- ¹

Step 2: 10-aryl-10-deacetoxy-13-0- (2,2,2-trichloroethoxycarbonyl) -7-0-trifluoromethanesulfonylbaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 5 of Example 1 to give the title compound as a colorless amorphous solid and colorless.

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.15 (s, 3H), 1.16 (s, 3H), 1.80 (s, 3H), 1.90 (d, 3H, J = lHz), 1.91 (m, 1H), 2.22 (m, lH), 2.38 (m, 1H), 2.40 (s, 3H), 2.52 (m, 1H), 2.80-2.90 (m, 2H), 4.18 (m, 3H), 4.35 (d, 1H, J = 8.0Hz), 4.85 (AB type d , 2H, J = 12Hz),

4.93 (d, 1H, J = 8.0Hz), 5.05 (dd, 1H, J = 2.0Hz, 12Hz),

 5.13 (dd, 1H, J = 2.0Hz, 17Hz), 5.60 (dd, 1H, J = 7.0Hz, 11Hz),

5.68 (d, 1H, J = 7.0Hz), 5,73 (m, 1H), 5.96 (t, 1H, J = 7.0Hz),

7.49 (t, 2H, J = 7.5Hz), 7.63 (m, 1H), 8.07 (m, 2H).

MS-FAB: 875 (MH ⁺ )

Step 3: 10-aryl-10-deacetoxy-7-deoxy-7 / 3,8 S-methylene-13-0- (2,2,2-trichloroethoxycarbonyl) -19-norpaccatin III

 20 mg of the compound obtained in the above step 2 was dissolved in a mixed solvent of 6 ml of dichloromethane and 5 ml of acetonitrile, and a large excess of silica gel (mesh 40-63) was added, followed by stirring at 80 ° C for 1.5 hours. The silica gel is removed by filtration, the filtrate is concentrated, and the obtained residue is subjected to silica gel thin layer chromatography (developing solvent; methylene chloride: hexane: acetone = 70: 30: 3 (v / v / v)) to give 13.2 mg of the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TS) (5 (ppm):

 1.14 (s, 3H), 1.19 (s, 3H), 1.53 (t, 1H, J = 6.0Hz), 1.82 (s, 3H),

1.90 (br, 1H), 2.10 (d, 1H, J = 17Hz), 2.22 (m, 2H), 2.34 (s, 3H),

2.40 (m, 2H), 2.46 (m, 1H), 3.00 (m, 1H), 3.71 (d, 1H, J = 7.0Hz),

 4.02 (d, 1H, J = 8.0Hz), 4.29 (d, 1H, J = 8.0Hz), 4.33 (d, 1H, J = 7.0Hz),

 4.74 (d, 1H, J = 1.0Hz), 4.84 (AB type d, 2H, J = 12Hz), 5.01 (d, 1H, J = 10.0Hz),

8 6 5.10 (d, 1H, J = 17Hz), 5.61 (d, 1H, J = 7.0Hz), 5.81 (m, 1H), 5.88 (m, 1H), 7.49 (t, 2H, J = 7.5Hz), 7.61 (t, 1H, J = 7.5Hz), 8.10 (d, 2H, J = 7.5Hz).

MS-FAB: 725 (H ⁺ )

Step 4: 10-aryl-10-deacetoxy-7-deoxy-7 / 3, 8 / 3-methylene-19-norbaccatin III

 13 mg of the compound obtained in the above step 3 was dissolved in a mixed solvent of 3 ml of acetic acid and 3 ml of methanol, 100 mg of zinc powder was added, and the mixture was stirred at 60 at 10 minutes. After zinc was removed by filtration and the filtrate was concentrated, the obtained residue was diluted with ethyl acetate, washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; black form: acetone = 95: 5 (v / v)) to give the title compound 7 as a colorless amorphous solid. Was.

Ή-NR (CDC / TMS) 5 (ppm):

 1.09 (s, 3H), 1.17 (s, 3H), 1.26 (m, 1H), 1.53 (m, 1H),

 1.88 (d, 1H, J = 1.0Hz), 1.94 (br, 1H), 2.09 (d, 1H, J = 16Hz), 2.22 (m, 1H), 2.26 (m, 2H), 2.27 (s, 3H) , 2.36 (dd, 1H, J = 7.0Hz, 16Hz),

2.43 (dt, 1H, J = 4.5Hz, 16Hz), 3.00 (m, 1H), 3.71 (dd, 1H, J = 6.0Hz, 8.0Hz), 4.02 (d, 1H, J = 8.0Hz), 4.30 ( d, 1H, J = 8.0Hz), 4.36 (d, 1H, J = 7.0Hz),

4.72 (d, 1H, J = 4.0Hz), 4.82 (m, 1H), 5.01 (d, 1H, J = 10.0Hz),

 5.10 (dd, 1H, J = l.5Hz, 17Hz), 5.60 (d, 1H, J = 7.0Hz), 5.82 (m, 1H),

7.49 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz), 8.11 (d, 2H, J = 7.5Hz).

MS-FAB: 550 (MH +)

Step 5: 10-aryl-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (te rt -butyldimethylsilyl) oxy-3-phenylpropionyl] -10 -Deacetoxy-7-deoxy-7 / 3,8 / 3-methylene-19-norpaccatin III

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TS) 5 (ppm):

 -0.35 (s, 3H), -0.12 (s, 3H), 0.71 (s, 9H), 1.21 (s, 3H), 1.22 (s, 9H), 1.24 (s, 3H), 1.55 (m, 1H) , 1.71 (s, 3H), 1.83 (br, 1H), 2.10 2.21 (m, 4H),

8 7 2.43 (m, 3H), 2.50 (s, 3H), 2.99 (m, 1H), 3.68 (t, 1H, J = 7.0Hz), ― 4.03 (d, 1H, J = 8.0Hz), 4.26 (d, 1H, J = 7.0Hz), 4.29 (d, 1H, J = 8.0Hz),

 4.47 (s, 1H), 4.78 (d, 1H, J = 4.0Hz), 5.03 (d, 1H, J = 8.0Hz),

 5.10 (d, 1H, J = 17Hz), 5.30 (m, 1H), 5.42 (m, 1H), 5.65 (d, 1H, J = 7.0Hz),

5.82 (m, lH), 6.29 (m, 1H), 7.25-7.36 (m, 5H), 7.48 (t, 2H, J-7.5Hz),

7.56 (t, 1H, J = 7.5Hz), 8.14 (d, 2H, J = 7.5Hz).

 MS-FAB: 928 (MH +)

Step 6: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-7-deoxy- 73,8 / 9-methylene-10- (2-morpholinoethyl) -19-norpaccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 -0.33 (s, 3H), -0.12 (s, 3H), 0.74 (s, 9H), 1.20 (s, 3H), 1.22 (s, 3H), 1.25 (s, 9H), 1.57 (m, 1H) , 1.80 (s, 3H), 2.12 (m, 2H), 2.20 (m, 1H),

2.35 (m, 2H), 2.44 (m, 6H), 2.52 (s, 3H), 2.55 (m, 1H), 3.70 (m, 4H),

3.75 (m, 1H), 4.06 (d, 1H, J = 8.5Hz), 4.28 (d, 1H, J = 7.0Hz),

4.31 (d, 1H, J = 7.0Hz), 4.50 (s, 1H), 4.79 (d, 1H, J = 3.0Hz),

 5.32 (d, 1H, J = 10.0Hz), 4.43 (d, 1H, J = 10Hz), 5.68 (d, 1H, J = 7.0Hz),

 6.28 (t, 1H, J = 7.0Hz), 7.28-7.35 (m, 5H), 7.48 (t, 2H, J = 7.5Hz),

 7.57 (t, 1H, J = 7.5Hz), 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 1001 (MH ⁺ )

Step 7: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-7-deoxy-73,8 / 3-Methylene -10- (2_ morpholinoethyl) -19-norpaccatin III

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 9 of Example 1 to give the title compound as a colorless solid.

Melting point: 120-125 ° C

Ή-NMR (CDCl3 / TMS) (5 (ppm):

8 8 1.20 (s, 3H), 1.22 (s, 3H), 1.27 (s, 9H), 1.56 (t, IH, J = 7. OHz),

 1.79 (s, 3H), 1.88 (s, IH), 2.12 (m, 1H), 2.20 (m, 3H), 2,35-2.48 (m, 12H),

2.43 (m, 6H), 2.55 (m, IH), 3.71 (m, 4H), 3.75 (m, IH),

 4.04 (d, IH, J = 8.5Hz), 4.27 (d, 1H, J = 7.OHz), 4.29 (d, IH, J = 7.OHz),

 4.60 (s, 1H), 4.75 (d, IH, J = 3. OHz), 5.29 (m, IH), 5.35 (d, IH, J = 10. OHz),

5.65 (d, IH, J = 7.0Hz), 6.22 (m, IH), 7.30-7.44 (m, 5H),

 7.50 (t, 2H, J = 7.5Hz), 7.60 (t, IH, J = 7.5Hz), 8.16 (d, 2H, J = 7.5Hz).

MS-FAB: 887 (MH +)

IR (KBr): 3448, 3068, 2972, 2932, 2860, 2812, 1720, 1684, 1604, 1586, 1494 cm— ¹

Example 19

89

Replacement paper (Kaikai IJ26)

Process 3

89/2 Replacement Form (Rule 26) Step 1: 10-aryl-10-deacetoxy-7-deoxy-7S, 83-methylene-13-0-triethylsilyl -19-norpaccatin 111

 182 mg of the compound obtained in Step 5 of Example 1 was dissolved in a mixed solvent of 10 ml of dried tetrahydrofuran and 10 ml of dried acetonitrile, and 5.5 g of silica gel (mesh 40-63 mm) was added. For 16 hours. Filter off the silica gel and filter

8 9/3

Replacement paper (Kaikai After concentration of the liquid, the obtained residue was purified by silica gel thin layer chromatography (developing solvent: methylene chloride: hexane: acetone = 70: 30: 3 (v / v / v)). 107 mg of the title compound were obtained as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) (5 (ppm):

 0.66 (m, 6H), 1.01 (t, 9H, J2 8. OHz), 1.13 (s, 3H), 1.17 (s, 3H),

1.52 (dd, 1H, J2 5.0Hz, 7.0Hz), 1.83 (d, 3H, J = lHz), 2.08 (d, 1H, J = 16Hz), 2.17 (m, 3H), 2.26 (s, 3H) , 2.30 (m, 1H), 2.45 (dt, 1H, J = 2Hz, 6Hz),

2.99 (m, lH), 3.70 (dd, 1H, J = 6.0Hz, 8.0Hz), 4.05 (d, 1H, J = 8.5Hz),

4.26 (d, 1H, J = 8.0Hz), 4.29 (d, 1H, J = 8.5Hz), 4.76 (d, 1H, J = 4.0Hz),

 4.87 (t, 1H, J = 7Hz), 5.01 (d, 1H, J = 10.0Hz), 5.10 (dd, 1H, J = 1.5Hz, 17Hz),

5.59 (d, 1H, J = 8.0Hz), 5.81 (m, 1H), 7.47 (t, 2H, J = 7.5Hz),

7.60 (t, 1H, J2 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 664 (MH ⁺ )

Step 2: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-1-0-dimethylsilyl-Ίβ, 8 / 3-methylene-13-0-triethylsilyl-19-norpaccatin 111 Obtained in step 1 above The obtained compound was reacted in the same manner as in Step 2 of Example 9 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDCh / TMS) <5 (ppm):

 -0.23 (d, 3H, J = 2.7Hz), 0.08 (d, 3H, J: 2.7Hz), 0.77 (m, 6H), 1.06 (s, 3H), 1.07 (t, 9H, J = 8.0Hz) , 1.18 (s, 3H), 1.54 (t, 1H, J = 6.0Hz), 1.82 (s, 3H), 2.05-2.18 (m, 4H), 2.31 (m, 1H), 2.55 (dd, 1H, J = 8.8Hz, 15.0Hz),

2.68 (dd, 1H, J = 3.3Hz, 15.0Hz), 2.99 (m, 1H), 3.46 (s, 1H),

3.62 (dd, 1H, J = 5.7Hz, 8.2Hz), 3.99 (d, 1H, J = 7.3Hz), 4.12 (d, 1H, J = 7.9Hz), 4.15 (d, 1H, J = 7.9Hz) , 4.57 (m, 1H), 4.68 (m, 2H), 5.02 (d, 1H, J = 10.0Hz), 5.12 (dd, 1H, J: 1.3 Hz, 17Hz), 5.76 (d, 1H, J = 7.3Hz), 5.82 (m, 1H),

7.45 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 681 (H ⁺ )

Step 3: 10-Alinole-4-0-cyclopropanecarbonyl-10-deacetoxy-4-deacetyl-7-deoxy-1-0-dimethylsilyl-7 / 3,83-methylene-13-0-triethylsy

9 0 Lil-19-norpaccatin III—The compound obtained in the above Step 2 was reacted in the same manner as in Step 3 of Example 2 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TS) (5 (ppm):

 -0.24 (d, 3H, J = 2.7Hz), 0.11 (d, 3H, J = 2.7Hz), 0.68 (m, 6H), 1.00 (m, 9H), 1.12 (s, 3H), 1.19 (s, 3H), 1.24 (m, 4H), 1.51 (t, 1H, J = 7.0Hz),

1.61 (m, lH), 1.72 (m, 1H), 1.80 (s, 3H), 2.05 (m, 1H), 2.16 (m, 1H),

2.31-2.40 (m, 4H), 2.96 (m, 1H), 3.62 (m, 1H), 4.13 (d, 1H, J = 8.0Hz),

4.19 (d, 1H, J = 8.0Hz), 4.21 (d, 1H, J = 8.0Hz), 4.54 (m, 1H),

 4.62 (d, 1H, J = 3.8Hz), 4.98 (d, 1H, J = 10.0Hz), 5.08 (d, 1H, J = 17Hz),

 5.69 (d, 1H, J = 7.0Hz), 5.81 (m, 1H), 7.46 (t, 2H, J = 7.5Hz),

7.58 (t, 1H, J = 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 749 (MH ⁺ )

Step 4: 10-aryl-4-0-cyclopropanecarbonyl-10-deacetoxy-4-deacetyl-7-deoxy-7 / 3,8 / 3-methylene-19-norpaccatin III

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) <5 (ppm):

 1.02 (m, 2H), 1.10 (s, 3H), 1.17 (s, 3H), 1.20-1.27 (m, 2H), 1.53 (m, 1H), 1.65 (m, 1H), 1.77 (m, 1H) , 1.85 (s, 3H), 2.06 (d, 1H, J = 17.1Hz),

2.19 (m, 2H), 2.25-2.30 (m, 2H), 2.39 (m, 1H), 2.99 (m, 1H),

 3.68 (dd, 1H, J: 6.3Hz, 7.8Hz), 4.06 (d, 1H, J = 8.5Hz), 4.30 (d, 1H, J = 8.5Hz),

4.32 (d, 1H, J = 7.8Hz), 4.68 (d, 1H, J = 3.9Hz), 4.80 (br, 1H),

 4.00 (dd, 1H, J = l.0Hz, 9.8Hz), 5.09 (dd, 1H, J = l.5Hz, 17.lHz),

 5.62 (d, 1H, J 7.8Hz), 5.82 (m, 1H), 7.48 (t, 2H, J = 7.5Hz),

7.61 (t, 1H, J = 7.5Hz), 8.14 (m, 2H).

 MS-FAB: 576 (MH +)

Step 5: 10-aryl-13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilyl) oxypropionyl] -4-〇-cyclopropa

9 1 Carbonyl-10-deacetoxy-4-deacetyl-7-deoxy-7 / 3,8 / 3-methylene-19-norpaccatin III

 The compound obtained in the above Step 4 and (3R, 4R) -tri (tert-butoxycarbonyl) -4- (2-furyl) -3- (triisopropylsilyl) oxy-2-azetidinone were prepared in Examples. The reaction was carried out in the same manner as in Step 8 of 1 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TS) <5 (ppm):

 1.00 (m, 21H), 1.21 (s, 3H), 1.24 (s, 3H), 1.27 (s, 9H), 1.10-1.30 (m, 4H),

1.52 (m, lH), 1.73 (s, 3H), 1.79 (m, 1H), 1.90 (m, 1H),

 2.08 (d, 1H, J = 17.1Hz), 2.19 (m, 3H), 2.38 (dt, 1H, J = 4.4Hz, 17.1Hz),

 2.48 (dd, 1H, J = 9.6Hz, 17.4Hz), 2.99 (m, 1H), 3.69 (t, 1H, J = 6.9Hz),

 4.05 (d, 1H, J = 8.6Hz), 4.29 (m, 2H), 4.62 (m, 1H), 5.02 (m, 2H),

 5.10 (d, 1H, J = 17.1Hz), 5.23 (d, 1H, J = 10.0Hz), 5.35 (d, 1H, J = 10.0Hz),

5.68 (d, 1H, J = 7.8Hz), 5.83 (m, 1H), 6.22 (m, 2H), 6.34 (m, 1H),

 7.34 (s, 1H), 7.49 (t, 2H, J = 7.5Hz), 7.56 (t, 1H, J = 7.5Hz),

 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 986 (H ⁺ )

Step 6: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (triisopropylsilinole) oxypropionyl] -4-0- Cyclopropanecarbonyl-10-deacetoxy-4-deacetyl-7-deoxy-7 / 3, 8 / 3-methylene-10- (2-morpholinoethyl)-19-norpaccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

1 H-NMR (CDC / TS) 5 (ppm):

 0.95-1.00 (m, 21H), 1.19 (s, 3H), 1.2 (s, 3H), 1.18-1.23 (m, 4H),

1.29 (s, 9H), 1.47 (m, 1H), 1.54 (m, 1H), 1.84 (s, 3H), 1.90 (m, 1H),

2.08 (d, 1H, J 16.1Ηζ), 2.19 (m, 2H), 2.33 (m, 1H), 2.40 (m, 1H),

2.43 (m, 4H), 2.48-2.53 (m, 2H), 3,69 (m, 4H), 3.74 (m, 1H),

 4.07 (d, 1H, J = 8.8Hz), 4.29 (m, 2H), 4.63 (m, 1H), 5.02 (s, 1H),

 5.23 (d, 1H, J = 9.7Hz), 5.36 (d, 1H, J = 9.7Hz), 5.67 (d, 1H, J = 7.8Hz),

9 2 6.20 (d, 1H, J = 8.5 Hz), 6.24 (m, 1H), 6.35 (m, 1H), 7.33 (m, 1H),

7.49 (t, 2H, J = 7.5Hz), 7.56 (t, 1H, J = 7.5Hz), 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 1059 (H ⁺ )

Step 7: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -4-0-cyclopropanecarbonyl-10 -Deacetoxy-4 -Decetyl-7 -Deoxy-7 3,8 S-Methylene-10- (2-morpholinoletyl) -19-norpaccatin Π 1

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 120-125. C

Ή-NM (CDC / TMS) 5 (ppm):

 1.02 (m, 2H), 1.16 (m, 2H), 1.20 (s, 3H), 1.23 (s, 3H), 1.28 (s, 9H),

1.47 (m, lH), 1.53 (m, 1H), 1.80 (s, 3H), 1.90 (m, 1H),

2.04 (d, 1H, J = 13.1 Hz), 2.20 (m, 2H), 2.37 (m, 2H), 2.75-2.42 (m, 6H), 2.44 ( m, 4H), 3.70 (m, 4H), 3.75 (m, 1H), 4.79 (AB type d, 2H, J = 8.5 Hz),

4.63 (d, 1H, J = 3.4Hz), 4.76 (m, 1H), 5.15 (d, 1H, J = 9.7Hz),

 5.39 (d, 1H, J = 9.7 Hz), 5.64 (d, 1H, J = 7.8 Hz), 6.23 (t, 1H, J = 8.3 Hz),

 6.30 (m, lH), 6.37 (m, 1H), 7.39 (s, 1H), 7.51 (t, 2H, J = 7.5Hz),

7.59 (t, 1H, J = 7.5Hz), 8.17 (d, 2H, J = 7.5Hz).

MS-FAB: 903 (MH ⁺ )

Example 20

9 3

Replacement paper (Kaikai IJ26)

93/1 Replacement paper (Kaikai IJ26) Step 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2 -— (te rt -butyldimethylsilyl) oxy-3-phenylpropionyl]- 4-0-cyclopropanecarbonyl-10-deacetoxy-4-deacetyl-7-deoxy-7 / 3,8-methylene-19-norpaccatin III

 The compound obtained in Step 4 of Example 19 was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TS) <5 (ppm):

 -0.30 (s, 3H), -0.09 (s, 3H), 0.74 (s, 9H), 1.00 (m, 2H), 1.09 (m, 2H), 1.21 (s, 3H), 1.28 (s, 9H) , 1.29 (s, 3H), 1.56 (m, 1H), 1.71 (s, 3H),

1.82 (br, 1H), 1.90 (m, 1H), 2.10 (d, 1H, J = 15.9Hz), 2.14-2.24 (m, 3H), 2.39 (dt, 1H, J-4.4H2, 15.9Hz), 2.50 (dd, 1H, J = 10.1Hz, 15.1Hz),

2.99 (m, 1H), 3.68 (t, 1H, J = 6.9Hz), 4.08 (d, 1H, J = 8.5Hz), 4.54 (s, 1H),

4.64 (d, 1H, J = 4.0Hz), 5.02 (d, 1H, J = 10.0Hz),

 5.08 (dd, 1H, J = 1.4Hz, 17.1Hz), 5.30 (d, 1H, J = 8.8Hz), 5.43 (d, 1H, J = 8.8Hz), 5.66 (d, 1H, J = 7.8Hz) , 5.86 (m, 1H), 6.25 (t, 1H, J = 8.3Hz),

 7.24-7.37 (m, 5H), 7.50 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz),

8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 954 (MH ⁺ )

Step 2: 13-0-[(2R, 3S) -3 (tert-butoxycarbonylamino) -2_ (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -4-0-cyclopropanecarbonyl- 10-Deacetoxy-4-deacetyl-7-Deoxy-73,8yS-methylene-10- (2-morpholinoethyl) -19-norpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) 5 (ppm):

 -0.30 (s, 3H), -0.09 (s, 3H), 0.76 (s, 9H), 1.02 (m, 2H), 1.12 (m, 2H), 1.21 (s, 3H), 1.25 (s, 3H) , 1.31 (s, 9H), 1.48 (m, 1H),

1.57 (t, 1H, J = 6.0Hz), 1.80 (s, 3H), 1.91 (m, 1H), 2.10 (d, 1H, J = 15.9Hz), 2.18 (m, 2H), 2.34 (m, 2H ), 2.42 (m, 4H), 2.50 (m, 4H), 3.70 (m, 5H),

9 4 4.08 (d, 1H, J = 8.5Hz), 4.26 (d, 1H, J = 7.7Hz), 4.30 (d, 1H, J = 8.5Hz),

4.54 (s, lH), 4.67 (d, 1H, J = 3.6Hz), 5.31 (d, 1H, J 9.0Hz),

 5.44 (d, 1H, J = 9.0Hz), 5.68 (d, 1H, J = 7.7Hz), 6.21 (t, 1H, J = 8.4Hz),

7.24-7.37 (m, 5H), 7.50 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J 7.5Hz),

8.15 (d, 2H, J = 7.5Hz).

 MS-FAB: 1026 (MH +)

Step 3: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -4-0-cyclopropanecarbonyl-10-deacetoxy-4 -Decetyl-7-dexoxy-7S, 83-methylene-10_ (2_ morpholinoethyl) -19-nor

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 130-135 ° C

Ή-NMR (CDCl ₃ / TS) (5 (ppiii):

 0.82 (m, 2H), 0.92 (m, 2H), 1.20 (s, 3H), 1.24 (s, 3H), 1.29 (s, 9H),

1.46 (m, 1H), 1.54 (m, 1H), 1.77 (s, 3H), 1.82 (m, 1H), 2.10 (m, 1H),

 2.20-2.24 (m, 2H), 2.33-2.48 (m, 9H), 2.58 (m, 1H), 3.70 (m, 4H),

 3.74 (m, 1H), 4.05 (d, 1H, J = 8.5Hz), 4.26 (d, 1H, J = 7.7Hz),

 4.30 (d, 1H, J = 8.5Hz), 4.61 (d, 1H, J = 3.3Hz), 4.69 (br, 1H),

 5.29 (s, 2H), 5.66 (d, 1H, J 7.7Hz), 6.18 (m, 1H), 7.30-7.39 (m, 5H),

7.52 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz), 8.17 (d, 2H, J = 7.5Hz).

MS-FAB: 913 (MH ⁺ )

9 5

TBSOSO,,.

 0 Process 4

Engineering

mm fe7 z / sz-ϊ 0 /, 61lz OAV:

Step 1: 10-aryl-10-deacetoxy-4-deacetinole-7-deoxy-4-〇-ethoxycarbonyl-1-0-dimethylsilyl-7,8 / 3-methylene-13-0-triethylsilyl 1 9-Norpaccatin ΠΙ

 The compound obtained in Step 2 of Example 19 was reacted in the same manner as in Step 3 of Example 9 to obtain the title compound as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TS} ) (5 (ppm):

 -0.24 (d, 3H, J = 2.7Hz), 0.11 (d, 3H, J = 2.7Hz), 0.68 (m, 6H),

1.02 (t, 9H, J = 8.0Hz), 1.12 (s, 3H), 1.19 (s, 3H), 1.24 (m, 1H),

1.39 (t, 3H, J = 7.2Hz), 1.49 (dd, 1H, J = 5.3Hz, 7.0Hz), 1.84 (s, 3H),

2.09 (d, 1H, J = 15.9Hz), 2.16 (m, 2H), 2.32 (m, 2H), 2.38 (m, 1H),

2.99 (m, 1H), 3.66 (dd, 1H, J = 6.6Hz, 7.2Hz), 4.12 (m, 2H),

 4.24 (d, 1H, J = 8.6Hz), 4.28 (d, 1H, J = 7.7Hz), 4.38 (m, 1H), 4.53 (m, 1H), 4.73 (d, 1H, J = 4.2Hz), 4.93 (t, 1H, J2 8.1Hz), 4.99 (dd, 1H, J = 1.7Hz, 10.1Hz),

5.09 (dd, 1H, J = 1.7Hz, 17.0Hz), 5.69 (d, 1H, J = 7.7Hz), 5.85 (m, 1H),

7.46 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.12 (m, 2H).

MS-FAB: 753 (MH ⁺ )

Step 2: 10-aryl-10-deacetoxy-4-deacetyl-7-deokin-4-0-ethokincarbonyl-7 yS, 8 / 3-methylene-19-norpaccatin

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

9 6/2

Replacement form (Rule 26) Ή-NMR (CDC1:, / TMS) 5 (ppm):

 0.99 (s, 3H), 1.17 (s, 3H), 1.37 (t, 3H, J = 7.5Hz), 1.51 (m, 1H),

 1.89 (d, 3H, J = 15.9Hz), 2.13 (d, 1H, J = 15.9Hz), 2.23 (m, 2H),

 2.28 (d, 1H, J = 9.0Hz), 2.37 (dd, 1H, J = 6.9Hz, 15.7Hz),

 2.43 (dt, 1H, J = 4.5Hz, 15.9Hz), 3.00 (m, 1H), 3.72 (dd, 1H, J = 6.3Hz, 7.6Hz),

4.05 (d, 1H, J = 8.6Hz), 4, 21 (m, 1H), 4.31 (m, 2H), 4.42 (d, 1H, J = 7.6Hz),

4.80 (m, 2H), 5.02 (d, 1H, J = 10.1Hz), 5.10 (dd, 1H, J = l.6Hz, 17.1Hz),

 5.63 (d, 1H, J = 7.6Hz), 5.84 (m, 1H), 7.49 (t, 2H, J = 7.5Hz),

7.60 (t, 1H, J = 7.5Hz), 8.14 (m, 2H).

MS-FAB: 580 (MH ⁺ )

Step 3: 10-Aryl-13-〇-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10-Deacetoxy-4-deacetinol-7-deoxy-4-0-ethoxycarbonyl -7/3, 8 / 3-methylene-19-norpaccatin 1 II

 The compound obtained in the above step 2 and (3R, 4R) -tri (tert-butoxycarbyl) -4- (2-furyl) -3- (tert-butyldimethylsilyl) oxy-2-azetidinone were prepared in Example 1. The reaction was carried out in the same manner as in step 8 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDC / TMS) 5 (ppm):

 0.14 (s, 3H), 0.04 (s, 3H), 0.89 (s, 9H), 1.21 (s, 3H), 1.24 (s, 3H), 1.29 (s, 9H), 1.38 (t, 1H, J = 6.9Hz), 1.54 (m, 1H), 1.74 (s, 3H),

1.82 (br, 1H), 2.14 (d, 1H, J = 15.9Hz), 2.10-2.25 (m, 3H), 2.40 (m, 1H), 2.48 (m, 1H), 2.99 (m, 1H), 3.69 (t, 1H, J = 6.9Hz), 4.06 (d, 1H, J = 8.7Hz),

4.31 (m, 3H), 4.52 (m, 1H), 4.71 (m, 1H), 4.78 (d, 1H, J = 4.0Hz),

 5.02 (d, 1H, J = 10.0Hz), 5.12 (dd, 1H, J = 1.7Hz, 17.1Hz),

 5.21 (d, 1H, J = 8.5Hz), 5.33 (d, 1H, J = 8.5Hz), 5.69 (d, 1H, J = 7.5Hz),

5.82 (m, 1H), 6.19 (m, 1H), 6.23 (m, 1H), 6.35 (m, 1H), 7.38 (m, 1H),

7.50 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.16 (d, 2H, J = 7.5Hz).

MASS-FAB: 948 (MH ⁺ )

Step 4: 13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyl

9 7 Dimethylsilyl) oxy-3- (2-furyl) propionyl] -10-deacetoxy-4-decetyl-7-deoxy-4-0-ethoxycarbonyl-7 / 3,8 / 3-methylene-10- (2-Morpholinoethyl) _19-Nolpaccatin III

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDCl ₃ / TMS) 5 (ppm):

 -0.14 (s, 3H), 0.04 (s, 3H), 0.79 (s, 9H), 1.21 (s, 3H), 1.22 (s, 3H), 1.31 (s, 9H), 1.40 (t, 3H, J = 7.5Hz), 1.54 (m, 1H), 1.73 (s, 4H),

2.14 (d, 1H, J = 15.9Hz), 2.14 (m, 1H), 2.20 (m, 1H), 2.30-2.60 (m, 8H), 3.69 (m, 4H), 3.75 (t, 1H, J = 6.6Hz), 4.06 (d, 1H, J = 8.5Hz), 4.31 (m, 3H),

4.54 (m, 1H), 4.72 (m, 1H), 4.78 (d, 1H, J = 4.0Hz), 5.21 (d, 1H, J = 10.0Hz),

5.33 (d, 1H, J = 10.0Hz), 5.69 (d, 1H, J = 7.6Hz), 6.17 (t, 1H, J2 8.0Hz),

 6.24 (m, 1H), 6.36 (m, 1H), 7.38 (m, 1H), 7.50 (t, 2H, J = 7, 5Hz),

 7.57 (t, 1H, J = 7.5Hz), 8.16 (d, 2H, J = 7.5Hz).

MS-FAB: 1021 (MH ⁺ )

Step 5: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetoxy-4-decetyl-7 -Deoxy-4-0-ethoxycarbonyl -7/3, 8 / 3-methylene-10- (2-morpholinoethyl) -19-norpaccatin III

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

_{Ή-NMR (CDC1 3 / TS} ) (5 (ppm):

 1.21 (s, 6H), 1.26 (m, 3H), 1.33 (s, 9H), 1.48 (m, 1H), 1.53 (m, 1H),

1.82 (s, 3H), 1.88 (s, 1H), 2.14 (d, 1H, J = 15.9Hz), 2.16-2.22 (m, 3H), 2.37-2.57 (m, 9H), 3.70 (s, 4H) , 3.74 (m, 1H), 4.06 (d, 1H, J = 8.5Hz),

4.20 (m, 1H), 4.31 (d, 1H, J = 7.6Hz), 4.34 (d, 1H, J = 8.5Hz), 4.46 (m, 1H), 4.68 (d, 1H, J = 3.4Hz), 4.78 (s, 1H), 5.21 (d, 1H, J = 9.7Hz),

5.31 (d, 1H, J = 9.7Hz), 5.69 (d, 1H, J = 7.6Hz), 6.14 (t, 1H, J = 8.4Hz),

6.35 (m, 2H), 7.43 (s, 1H), 7.50 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz),

9 8 8.16 (d.2H, J = 7.5Hz).

MS-FAB: 907 (Μ)

Example 2

Replacement form (Rule 26)

99/1 Replacement sheet (Rule 26) Step 1: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-1-0-dimethylsilyl-4-0-methoxyacetyl-7 / 3,8; 3-methylene-13-0-triethylsilyl- 19- Norpaccatin III

 The compound obtained in Step 2 of Example 19 was reacted in the same manner as in Step 3 of Example 2 except that cyclopropane chloride luponyl was replaced with methoxyacetyl chloride to give the title compound as a colorless amorphous solid.

1 H-NMR (CDCh / TMS) (5 (ppm):

 -0.24 (d, 3H, J = 2.7Hz), 0.11 (d, 3H, J = 2.7Hz), 0.68 (m, 6H),

1.02 (t, 9H, J = 8.0Hz), 1.10 (s, 3H), 1.19 (s, 3H), 1.22 (m, 1H),

1.52 (m, 1H), 1.80 (s, 3H), 2.09 (d, 1H, J = 15.9Hz), 2.18 (m, 2H),

 2.32 (m, 2H), 2.46 (dt, 1H, J = 4.5Hz, 16.0Hz), 2.99 (m, 1H), 3.55 (s, 3H),

3.66 (m, 1H), 4.12 (m, 2H), 4.16 (d, 1H, J = 16.1Hz), 4.17 (d, 1H, J = 8.5Hz),

4.22 (d, 1H, J = 7.6Hz), 4.28 (d, 1H, J = 8.5Hz), 4.35 (d, 1H, J = 16.1Hz),

 4.53 (m, lH), 4.79 (d, 1H, J = 3.7Hz), 4.92 (t, 1H, J = 8.1Hz),

 5.00 (d, 1H, J = 10.1Hz), 5.09 (d, 1H, J = 17.0Hz), 5.67 (d, 1H, J = 7.6Hz),

 5.83 (m, lH), 7.46 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.18 (m, 2H).

MS -FAB: 753 (MH +)

Step 2: 10-aryl-10-deacetoxy-4-decetyl-7-deoxy-4-0-methoxy

9 9/2

Replacement form (Rule 26) Acetyl-7 / 3,8 / S Methylene-19-norpaccatin HI

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TS} ) 5 (ppm):

 1.09 (s, 3H), 1.17 (s, 3H), 1.54 (m, 1H), 1.87 (s, 3H), 2.14 (m, 2H),

 2.20-2.27 (m, 3H), 2.32 (dd, 1H, J = 7.0Hz, 16.0Hz),

 2.48 (dt, 1H, J = 4.5Hz, 16.0Hz), 2.99 (m, 1H), 3.57 (s, 3H),

 3.71 (dd, 1H, J = 6. lHz, 7.9Hz), 4.08 (m, 1H), 4.24 (AB type q, 2H, J 15.7Hz),

4.31 (d, 1H, J = 8.6Hz), 4.37 (d, 1H, J = 7.7Hz), 4.79 (m, 2H),

 5.01 (d, 1H, J = 10.1Hz), 5.10 (dd, 1H, J = 1.7Hz, 17.0Hz),

 5.62 (d, 1H, J 7.7Hz), 5.84 (m, 1H), 7.48 (t, 2H, J = 7.5Hz),

7.61 (t, 1H, J = 7.5Hz), 8.16 (m, 2H).

MS-FAB: 580 (MH ⁺ )

Step 3: 10-Aaryl-13-0-[(2R, 3R) _3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl ]-10-Deacetoxy-4-Decetyl-7 -Deoxy-4-0-Methoxyacetyl-7 / 3,8 / 3-Methylene-19-Norre Paccatin ΙΠ

 The compound obtained in the above Step 2 and (3R, 4R) -1- (tert-butoxycarbonyl) -4- (2-furyl) -3- (tert-butyldimethylnyl) oxy-2-azetidinone were used in Examples. The reaction was carried out in the same manner as in step 8 of 1 to give the title compound as a colorless amorphous solid.

Ή-NM (CDCh / TMS) 5 (ppm):

 -0.13 (s, 3H), -0.03 (s, 3H), 0.80 (s, 9H), 1.21 (s, 6H), 1.31 (s, 9H),

 1.54 (m, lH), 1.60 (s, 1H), 1.72 (s, 3H), 2.14 (d, 1H, J = 15.9Hz),

 2.14-2.25 (m, 3H), 2.41 (dd, 1H, J = 9.3Hz, 15.5Hz),

 2.48 (dt, 1H, J = 4.5Hz, 15.9Hz), 2.99 (m, 1H), 3.69 (t, 1H, J = 7.0Hz),

 4.08-4.15 (m, 2H), 4.31 (m, 2H), 4.79 (m, 3H), 5.02 (d, 1H, J = 10.1Hz),

5.12 (d, 1H, J = 17.1Hz), 5.36 (d, 1H, J = 9.6Hz), 5.65 (m, 2H), 5.83 (m, 1H),

6.20 (m, 1H), 6.22 (m, 1H), 6.35 (m, 1H), (d, 1H, J = 8.5Hz),

5.69 (d, 1H, J = 7.5Hz), 5.82 (m, 1H), 6.19 (m, 1H), 6.23 (m, 1H),

1 0 0 6.35 (m, lH), 7.39 (s, 1H), 7.48 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 948 (MH ⁺ )

Step 4: 13-0-[(2R, 3R) -3_ (tert-butoxycarbonylamino) _2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10-deacetoxy- 4-Decetyl-7-deoxy-4-0-Methoxyoxycetyl-7 / 3,8-methylene-10- (2-morpholinoethyl) -19-norpaccatin III

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) 5 (ppm):

 -0.12 (s, 3H), -0.03 (s, 3H), 0.80 (s, 9H), 1.19 (s, 6H), 1.31 (s, 9H), 1.48 (m, 1H), 1.54 (m, 1H) , 1.78 (s, 1H), 1.80 (s, 3H), 2.10-2.18 (m, 2H),

2.22 (m, 1H), 2.30-2.60 (m, 10H), 3.53 (s, 3H), 3.69 (m, 4H),

 3.78 (t, 1H, J = 6.0Hz), 4.07-4.17 (m, 2H), 4.30 (m, 3H), 4.79 (m, 2H),

4.82 (d, 1H, J = 16.0Hz), 5.33 (d, 1H, J = 10.0Hz), 5.59 (d, 1H, J = 10.0Hz),

5.65 (d, 1H, J = 7.5Hz), 6.18 (t, 1H, J = 8.5Hz), 6.22 (m, 1H), 6.35 (m, 1H),

7.38 (m, lH), 7.48 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz),

 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 1021 (MH ⁺ )

Step 5: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetoxy-4-decetyl-7 -Deoxy-4-0-methoxyacetyl-7 / 3,8-methylene-10- (2-morpholinoethyl) -19-norpaccatine III

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 1.19 (s, 6H), 1.33 (s, 9H), 1.48 (m, 1H), 1.56 (m, 1H), 1.80 (s, 3H),

 2.13 (d, 1H, J = 16.0Hz), 2.22 (m, 3H), 2.30-2.60 (m, hired), 3.50 (s, 3H),

3.70 (m, 4H), 3.78 (m, 1H), 4.06 (d, 1H, J = 8.6Hz), 4.12 (d, 1H, J = 17.0Hz),

1 0 1 4.30 (d, lH, J = 7.6Hz), 4.31 (m, IH), 4.62 (d, IH, J = 17. OHz), 4.76 (s, 1H),

4.79 (s, lH), 5.37 (s, 2H), 5.66 (d, 1H, J = 7.6Hz), 6.19 (br, 1H),

 6.32 (s, lH), 6.36 (m, IH), 7.41 (m, 1H), 7.48 (t, 2H, J2 7.5Hz),

 7.59 (t, IH, J = 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 907 (MH ⁺ )

Example 23

1 0 2

Replacement paper (Kaikai IJ26)

102/2 Replacement Form (Rule 26) Step 1: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-1-0-dimethylsilyl-7 / 3, 8 / 3-methylene-4-0-propionyl-13-0-triethylsilyl-19- Nor Packatin III

 The compound obtained in Step 2 of Example 19 was reacted in the same manner as in Step 3 of Example 2 except that propionyl chloride was used in place of propionyl chloride to give the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 -0.23 (d, 3H, J = 2.7Hz), 0.10 (d, 3H, J = 2.7Hz), 0.68 (m, 6H),

 1.02 (t, 9H, J = 8.0Hz), 1.11 (s, 3H), 1.19 (s, 3H), 1.22 (t, 3H, J = 7.5Hz),

1.25 (m, lH), 1.48 (m, 1H), 1.81 (s, 3H), 2.07 (d, 1H, J = 15.9Hz),

 2.18 (m, 2H), 2.33 (m, 2H), 2.45 (dt, 1H, J = 4.5Hz, 15.8Hz), 2.60 (m, 2H),

2.99 (m, 1H), 3.66 (t, 1H, J = 6.9Hz), 4.12 (d, 1H, J = 8.5Hz),

 4.20 (d, 1H, J = 7.6Hz), 4.24 (d, 1H, J = 8.5Hz), 4.53 (m, 1H),

 4.70 (d, 1H, J = 4.0Hz), 4.92 (t, 1H, J = 8.2Hz), 4.99 (d, 1H, J = 10.1Hz),

 5.09 (d, 1H, J = 17.0Hz), 5.67 (d, 1H, J = 7.6Hz), 5.83 (m, 1H),

 7.46 (t, 2H, J = 7.5H2), 7.59 (t, 1H, J = 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

1 0 2/3

Replacement form (Rule 26) MS -FAB: 737 (ΜΗ ')

Step 2: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-7 / 3, 8 / 3-methylen-4-〇-propionyl-19-norpaccatin 111

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) (5 (ppm):

 1.09 (s, 3H), 1.17 (s, 3H), 1.26 (t, 3H, J = 7.1Hz), 1.53 (m, 1H),

 1.87 (s, 3H), 1.99 (s, 1H), 2.09 (d, 1H, J = 15.9Hz), 2.20 (m, 3H),

 2.34 (dd, 1H, J 7.0Hz, 15.9Hz), 2.57 (m, 1H), 2.65 (m, 1H), 2.99 (m, 1H),

3.71 (m, 1H), 4.06 (d, 1H, J = 8.5Hz), 4.29 (d, 1H, J = 8.5Hz),

 4.36 (d, 1H, J = 7.6Hz), 4.71 (d, 1H, J = 3.2Hz), 4.83 (br, 1H),

 4.99 (d, 1H, J = 9.9Hz), 5.09 (d, 1H, J = 17.0Hz), 5.61 (d, 1H, J = 7.6Hz),

 5.83 (m, lH), 7.46 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz),

 8.14 (d, 2H, J = 7.5Hz).

MS-FAB: 564 (H ⁺ )

Step 3: 10-Aryl-13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propioni 10-Deacetoxy-4-deacetyl-7-deoxy-7 / 3,8 / 3-methylene-4-0-propionyl-19-norbaccatin 111

 The compound obtained in the above step 2 and (3R, 4R) -1- (tert-butoxycarbonyl) -4- (2-furyl) -3- (tert-butyldimethylsilyl) oxy-2-azetidinone were used in Examples. The reaction was carried out in the same manner as in step 8 of 1 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TS) (5 (ppin):

 -0.17 (s, 3H), 0.02 (s, 3H), 0.80 (s, 9H), 1.21 (s, 3H), 1.22 (s, 3H),

1.27 (s, 9H), 1.32 (t, 3H, J = 7.5Hz), 1.55 (m, 1H), 1.72 (s, 3H),

 1.80 (br, lH), 2.12 (d, 1H, J = 15.9Hz), 2.14-2.25 (m, 3H), 2.42 (m, 1H),

2.46 (m, 1H), 2.74 (m, 2H), 2.99 (m, 1H), 3.69 (t, 1H, J = 7.0Hz),

 4.06 (d, 1H, J 8.5Hz), 4.24 (d, 1H, J = 7.6Hz), 4.30 (d, 1H, J = 8.5Hz),

 4.70 (s, 2H), 5.04 (d, 1H, J = 10.1Hz), 5.11 (dd, 1H, J = 1.7Hz, 17.1Hz),

1 0 3 5.22 (d, 1H, J = 10.0Hz), 5.31 (d, 1H, J = 10.0Hz), 5.66 (d, 1H, J = 7.6Hz),

5.82 (m, lH), 6.22 (m, 2H), 6.36 (m, 1H), 7.39 (s, 1H),

7.48 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.16 (d, 2H, J = 7.5Hz).

MS-FAB: 932 (MH +)

Step 4: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10-deacetoxy- 4-decetyl-7-deoxy-7yS, 8-methylene-10- (2-morpholinoethyl) _4-0-propionyl-19-norpaccatin III

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) (5 (ppm):

 -0.17 (s, 3H), 0.02 (s, 3H), 0.80 (s, 9H), 1.20 (s, 3H), 1.21 (s, 3H), 1.28 (s, 9H), 1.34 (t, 3H, J = 7.5Hz), 1.48 (m, 1H), 1.55 (m, 1H),

1.78 (s, lH), 1.80 (s, 3H), 2.12 (d, 1H, J = 15.9Hz), 2.13-2.21 (m, 2H), 2.30-2.54 (m, 10H), 2.75 (m, 2H) , 3.70 (m, 4H), 3.74 (m, 1H),

4.06 (d, 1H, J = 8.5Hz), 4.26 (d, 1H, J = 7.6Hz), 4.30 (d, 1H, J = 8.5Hz),

 4.72 (s, 2H), 5.23 (d, 1H, J = 10.0Hz), 5.31 (d, 1H, J = 10.0Hz),

 5.66 (d, 1H, J = 7.6Hz), 6.21 (m, 1H), 6.23 (m, 1H), 6.36 (s, 1H),

7.39 (s, lH), 7.48 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz),

 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 1004 (MH ⁺ )

Step 5: 13-0 [(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2- (hydroxypropionyl) -10-deacetoxy-4-deacetinol-7- Deoxya /? ^^-Methylene-10- (2-morpholinoletyl) -4-〇-propionyl-19-norbaccatin 111 The compound obtained in the above Step 4 is reacted in the same manner as in Step 9 of Example 1 to give the title compound as a colorless Obtained as a solid.

Ή-NMR (CDCl ₃ / TS) (5 (ppm):

 1.21 (s, 3H), 1.23 (s, 3H), 1.27 (s, 9H), 1.48 (m, 1H), 1.55 (m, 1H),

1.81 (s, 3H), 1.88 (br, 1H), 2.14 (d, 1H, J = 16.0Hz), 2.19 (m, 2H),

1 0 4 2.30-2.60 (m, 10H), 2.72 (m, 2H), 3.72 (m, 5H), 4.03 (d, IH, J = 8.5Hz),

4.23 (d, 1H, J = 7.6 Hz), 4.30 (d, 1H, J = 8.5 Hz), 4.70 (s, 2H),

 5.19 (d, 1H, J = 10.0 Hz), 5.31 (d, IH, J = 10. OHz), 5.64 (d, IH, J-7.6 Hz),

6.23 (m, 1H), 6.31 (br, 1H), 6.38 (s, 1H), 7.43 (s, IH),

 7.48 (t, 2H, J = 7.5Hz), 7.59 (t, IH, J = 7.5Hz), 8.18 (d, 2H, J = 7.5Hz). MS-FAB: 891 (MH +)

Example 2 4

1 0 5

Replacement paper (Kaikai IJ26)

105/2 Replacement Form (Rule 26) Step 1: 10-aryl-4-0-butanoyl-10-deacetoxy-4-deacetyl-7-deoxy-1-0-dimethylsilyl-7 / 3,8; 5-methylene-13-0-triethylsilyl- 19-Norva kachin I II

The compound obtained in Step 2 of Example 19 was reacted in the same manner as in Step 3 of Example 2 except that luponyl chloride was replaced with _n- butyryl chloride in Step 3 of Example 2 to obtain the title compound as a colorless amorphous solid.

1 H-NMR (CDCh / TMS) 5 (ppm):

 -0.23 (d, 3H, J-2.7Hz), 0.10 (d, 3H, J = 2.7Hz), 0.68 (m, 6H),

 1.02 (t, 9H, J = 8.0Hz), 1.04 (t, 3H, J = 7.5Hz), 1.10 (s, 3H), 1.19 (s, 3H),

1.22 (m, lH), 1.48 (m, 1H), 1.78 (m, 2H), 1.80 (s, 3H),

 2.09 (d, 1H, J = 15.9Hz), 2.18 (m, 2H), 2.33 (m, 2H),

 2.45 (dt, lH, J = 4.5Hz, 15.9Hz), 2.52 (m, 2H), 2.99 (m, 1H), 3.67 (m, 1H),

4.12 (d, 1H, J = 8.5Hz), 4.22 (d, 1H, J = 8.1Hz), 4.24 (d, 1H, J = 8.5Hz),

1 0 5/3

Replacement forms (Rule 26) 4.53 (m, 1H), 4.70 (d, 1H, J = 3.9Hz), 4.92 (t, 1H, J: 8.2Hz),

 4.99 (d, 1H, J = 10.1Hz), 5.09 (d, 1H, J = 17.0Hz), 5.67 (d, 1H, J = 8.1Hz),

 5.83 (m, 1H), 7.46 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz),

8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 751 (MH ⁺ )

Step 2: 10-aryl-4-0-butanoyl-10-deacetoxy-4-deacetyl-7-deoxy-7 / 3,8-methylene-19-norpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 1.09 (s, 3H), 1.17 (s, 3H), 1.28 (t, 3H, J = 7.5Hz), 1.53 (m, 1H),

 1.74 (m, 2H), 1.86 (d, 3H, J = l.1Hz), 1.92 (m, 1H), 2.09 (d, 1H, J = 15.9Hz),

2.18-2.27 (m, 3H), 2.34 (dd, 1H, J = 7.0Hz, 15.6Hz),

 2.46 (dt, 1H, J = 4.5Hz, 15.6Hz), 2.53 (m, 1H), 2.59 (m, 1H), 2.99 (m, 1H), 3.71 (m, lH), 4.06 (d, 1H, J = 8.5Hz), 4.29 (d, 1H, J = 8.5Hz),

 4.36 (d, 1H, J = 7.6Hz), 4.71 (d, 1H, J = 3.9Hz), 4.83 (br, 1H),

 5.01 (d, 1H, J = 9.9Hz), 5.10 (dd, 1H, J = 1.7Hz, 17.0Hz), 5.61 (d, 1H, J = 7.6Hz),

5.83 (m, lH), 7.48 (t, 2H, J = 7.5Hz), 7.61 (t, 1H, J = 7.5Hz),

8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 578 (MH ^† )

Step 3: 10-aryl-4-0-butanoyl-13-〇-[(2R, 3R) -3 (tert-butoxycarbonylanilamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl ) Propionyl] -10-deacetoxy-4-deacetyl-7-deoxy-7 8 / 3-methylene-19-norbactin

 The compound obtained in the above Step 2 and (3R, 4R) -1- (tert-butoxycarbonyl) -4- (2-furyl) -3- (tert-butyldimethylsilyl) oxy-2-azetidinone were used in Examples. The reaction was performed in the same manner as in step 8 of 1 to give the title compound as a colorless amorphous solid.

Ή-NR (CDCh / TS) (5 (ppm):

 -0.17 (s, 3H), 0.02 (s, 3H), 0.80 (s, 9H), 1.01 (t, 3H, J = 7.5Hz),

1 0 6 1.21 (s, 3H), 1.23 (s, 3H), 1.28 (s, 9H), 1.55 (t, 111, J = 7.5Hz),

1.72 (s, 3H), 1.78-1.87 (m, 3H), 2.14 (d, 1H, J = 15.9Hz), 2.11-2.24 (m, 3H),

2.39-2.48 (m, 2H), 2.65 (m, 1H), 2.72 (m, 1H), 2.99 (m, 1H),

 3.69 (t, 1H, J = 6.8Hz), 4.06 (d, 1H, J = 8.5Hz), 4.28 (d, 1H, J = 7.6Hz),

4.31 (d, 1H, J = 8.5Hz), 4.72 (s, 2H), 5.03 (d, 1H, J = 10.0Hz),

 5.12 (d, 1H, J = 17.1Hz), 5.23 (d, 1H, J = 10.0Hz), 5.33 (d, 1H, J = 10.0Hz), 5.65 (d, 1H, J = 7.6Hz), 5.83 ( m, 1H), 6.21 (m, 2H), 6.37 (m, 1H),

7.37 (s, 1H), 7.48 (t, 2H, J: 7.5Hz), 7.57 (t, 1H, J = 7.5Hz),

8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 946 (MH ⁺ )

Step 4: 4- 0-butanoyl -13-〇-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tertbutyldimethylsilyl) oxy-3- (2-furyl) propioni ] -10-Deacetoxy-4-deacetyl-7-deoxy-7; 3,8 / 3-methylene-10- (2-morpholinoethyl) -19-norpaccatin III

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

1 H-NMR (CDC / TMS) (5 (ppm):

 -0.15 (s, 3H), 0.02 (s, 3H), 0.80 (s, 9H), 1.01 (t, 3H, J: 7.5Hz),

1.19 (s, 3H), 1.20 (s, 3H), 1.29 (s, 9H), 1.48 (m, 1H), 1.55 (m, 1H),

1.81 (s, 3H), 1.82 (m, 2H), 2.08-2.20 (m, 3H), 2.30-2.55 (m, 10H),

2.66-2.72 (m, 2H), 3.70 (s, 4H), 3.75 (m, 1H), 4.06 (d, 1H, J = 8.5Hz),

 4.28 (d, 1H, J = 7.3Hz), 4.31 (d, 1H, J = 8.5Hz), 4.72 (s, 2H),

 5.22 (d, 1H, J = 10.0Hz), 5.34 (d, 1H, J = 10.0Hz), 5.64 (d, 1H, J2 7.3Hz),

6.19 (m, 1H), 6.21 (s, 1H), 6.35 (m, 1H), 7.38 (s, 1H),

 7.48 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 1018 (MH

Step 5: 4 O Butanoyl-13-O-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroquininepropionyl] -10-deacetoxy-4 -Decetyl-7 -Doxy-7 / 3, 8 / 3-methylene-10 (2-morpholinoethyl) -19-norpaccatin III

1 0 7 The compound obtained in the above Step 4 was subjected to RJt in the same manner as in Step 9 of Example 1 to give the title compound as a colorless solid.

Ή-NMR (CDCl ₃ / TMS) <5 (ppm):

 0.98 (t, 3H, J = 7.5Hz), 1.21 (s, 6H), 1.28 (s, 9H), 1.48 (m, 1H),

 1.55 (m, 1H), 1.77 (m, 2H), 1.80 (s, 3H), 1.88 (s, 1H),

 2.10 (d, 1H, J = 15.6Hz), 2.20 (m, 2H), 2.30-2.70 (m, 12H), 3.70 (s, 4H),

 3.74 (m, lH), 4.06 (d, 1H, J = 8.5Hz), 4.28 (d, 1H, J = 7.5Hz),

 4.29 (d, 1H, J = 8.5Hz), 4.69 (s, 2H), 5.18 (d, 1H, J = 10.0Hz),

 5.32 (d, 1H, J = 10.0Hz), 5.64 (d, 1H, J = 7.5Hz), 6.21 (m, 1H), 6.32 (s, 1H),

6.36 (s, lH), 7.41 (s, 1H), 7.49 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz), 8.17 (d, 2H, J2 7.5Hz).

MS-FAB: 904 (MH ⁺ )

Example 25

1 08

Replacement form (Rule 26)

108/1 Replacement sheet (Rule 26) Step 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10- Deacetoxy-4-deacetinole-7-deoxy-4-0-ethoxycarbonyl-73,83-methylene-19-norbaccatin II 1

 Example 21 The compound obtained in Step 2 of 1 was reacted in the same manner as in Step 8 of Example 1 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) <5 (ppm):

1 0 8/2

Replacement form (Rule 26) 0.30 (s, 3H), -0.10 (s, 3H), 0.77 (s, 9H), 1.22 (s, 311), 1.24 (s, 3H), 1.31 (s, 9H), 1.33 (m, 3H), 1.54 (m, 1H), 1.59 (s, 1H), 1.74 (s, 3H),

 1.83 (br, 1H), 2.14 (d, 1H, J = 15.9Hz), 2.18-2.27 (m, 3H),

 2.42 (dt, 1H, J = 4.5Hz, 15.9Hz), 2.55 (dd, 111, J = 9.3Hz, 15.5Hz), 3.00 (m, 1H),

3.69 (t, 1H, J = 6.9Hz), 4.11 (d, 1H, J = 8.5Hz), 4.27 (m, 1H), 4.32 (m, 2H), 4.46 (s, lH), 4.49 (m, 1H ), 4.77 (d, 1H, J2 4.0Hz), 5.03 (d, 1H, J = 10.0Hz), 5.10 (d, 1H, J = 17.1Hz), 5.28 (d, 1H, J = 10.0Hz), 5.43 (d, 1H, J = 10.0Hz),

5.68 (d, 1H, J = 7.6Hz), 5.82 (m, 1H), 6.18 (m, 1H), 7.28-7.40 (m, 5H),

7.46 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 958 (MH ⁺ )

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-4- Deacetyl-7-deoxy-4-0-ethoxycarbonyl-7 / 3,8 / 3-methylene-10- (2-morpholinoethyl) -19-norpaccatin ΠΙ

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

 Ή-NR (CDC1;, / TMS) (5 (ppm):

 -0.30 (s, 3H), 0.12 (s, 3H), 0.77 (s, 9H), 1.20 (s, 3H), 1.1 (s, 3H), 1.31 (s, 9H), 1.35 (m, 3H ), 1.50 (m, 1H), 1.54 (s, 1H), 1.82 (s, 4H),

2.12-2.20 (m, 4H), 2.302.59 (m, 9H), 3.70 (s, 4H), 3.75 (m, 1H),

4.10 (m, 1H), 4.29 (m, 1H), 4.33 (m, 2H), 4.46 (s, 1H), 4.52 (m, 1H),

 4.79 (s, lH), 5.29 (m, 1H), 5.42 (m, 1H), 5.68 (d, 1H, J = 7.6Hz),

6.16 (m, 1H), 7.28-7.37 (m, 5H), 7.46 (t, 2H, J = 7.5Hz),

 7.57 (t, 1H, J two 7.5Hz), 8.15 (d, 2H, J two 7.5Hz).

MS-FAB: 1031 (H ⁺ )

Step 3: 13-0 [(2R, 3S) -3 (tert-butoxycarbonylamino) -2-hydroxy-3- phenylpropionyl] -10-deacetoxy-4-deacetyl-7-deoxy-4-0- Ethoxycarbonyl-7 / 5, 8 / 3-methylene-10- (2-morpholinoletyl) -19-norpacacci

1 0 9 The compound obtained in the above Step 2 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 115-120 ° C

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.20 (s, 3H), 1.23 (s, 3H), 1.31 (s, 9H), 1.49 (m, 1H), 1.52 (m, 1H), 1.77 (s, 3H), 1.76 (s, 1H), 2.14 (d, 1H, J = 15.9Hz), 2.20 (m, 3H),

2.31-2.59 (m, 9H), 3.70 (s, 4H), 3.73 (m, 1H), 4.08 (d, 1H, J = 8.5Hz), 4.10 (m, 1H), 4.32 (m, 3H), 4.58 (s, 1H), 4.78 (s, 1H), 5.26 (m, 1H), 5.36 (m, 1H), 5.68 (d, 1H, J = 7.6Hz), 6.09 (s, 1H), 7.28-7.45 ( m, 5H), 7.49 (t, 2H, J = 7.5Hz), 7.59 (t, 1H, J = 7.5Hz), 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 917 (MIT)

Example 26

1 1 0

Replacement form (Rule 26)

Step 1: 10-aryl-13-0-[(2R, 3S) _3 (tert-butoxycarbonylamino) -2- (te rt-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-4 -Deacetyl-7-deoxy-4-0-methoxyacetyl-7 / 3,8 / 3-methylene-19-norebaccatin 111

 The compound obtained in Step 2 of Example 22 was reacted in the same manner as in Step 8 of Example 1 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TS) 5 (ppm):

 -0.30 (s, 3H), -0.28 (s, 3H), 0.73 (s, 9H), 1.22 (s, 3H), 1.24 (s, 3H),

1 1 0/2

Replacement form (Rule 26) 1.31 (s, 9H), 1.54 (m, 111), 1.58 (s, 1H), 1.76 (s, 3H), 1.79 (br, 1H),

2.14 (m, 2H), 2.22 (m, 2H), 2.43 (dd, 1H, J = 7.7Hz, 15.4Hz), 2.49 (m, 1H),

2.99 (m, lH), 3.59 (s, 3H), 3.70 (m, 1H), 4.11 (d, 1H, J = 8.5Hz),

 4.12 (d, 1H, J = 16.0Hz), 4.30 (d, 1H, J = 7.6Hz), 4.31 (d, 1H, J = 8.5Hz),

 4.62 (s, 1H), 4.80 (d, 1H, J = 2.5Hz), 4.91 (d, 1H, J = 16.0Hz),

 5.03 (d, 1H, J = 10.0Hz), 5.10 (d, 1H, J = 17.1Hz), 5.29 (d, 1H, J = 10.0Hz), 5.68 (d, 1H, J = 7.6Hz), 5.82 ( m, 1H), 6.09 (m, 1H), 6.21 (m, 1H),

 7.28-7.36 (m, 5H), 7.48 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz),

8.10 (d, 2H, J = 7.5Hz).

MS-FAB: 958 (MH ⁺ )

Step 2: 130 [(2R, 3S) 3 (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-4-deacetyl-7 -Doxy-4-0-methoxyacetyl-7 / 3,8 / 3-methylene-10- (2-morpholinoethyl) -19-norpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TMS} ) (5 (ppm):

 -0.30 (s, 3H), 0.28 (s, 3H), 0.73 (s, 9H), 1.19 (s, 3H), 1.20 (s, 3H), 1.31 (s, 9H), 1.49 (m, 1H), 1.53 Cm, 1H), 1.80 (s, 1H), 1.83 (s, 3H),

 2.05-2.23 (m, 4H), 2.30-2.60 (m, 9H), 3.59 (s, 3H), 3.70 (s, 4H),

 3.78 (m, 1H), 4.09 (d, 1H, J = 8.5Hz), 4.17 (d, 1H, J = 17.3Hz), 4.32 (m, 2H),

4.62 (s, 1H), 4.82 (m, 1H), 4.93 (d, 1H, J = 17.3Hz), 5.29 (d, 1H, J = 10.0Hz),

5.68 (d, 1H, J = 7.6Hz), 6.03 (m, 1H), 6.20 (t, 1H, J = 8.0Hz),

7.35-7.36 (m, 5H), 7.48 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz),

8.10 (d, 2H, J = 7.5Hz).

MS-FAB: 1031 (MH ⁺ )

Step 3: 13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylphenyl) 10 deacetin-4 deacetyl-7-dequin-4 -0-Methoxyxycetyl -7/3, 8 /?-Methylene-10- (2-morpholinoethyl) 19-norbaccatin 1

1 1 1 II

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 115-120 ° C

1 H-NMR (CDCh / TMS) 5 (ppm):

 1.19 (s, 6H), 1.31 (s, 9H), 1.49 (m, 1H), 1.55 (m, 1H), 1.80 (s, 4H), 2.14 (d, 1H, J = 15.9Hz), 2.22 "( m, 3H), 2.30-2.60 (m, 9H), 3.50 (s, 3H),

3.70 (s, 4H), 3.78 (m, 1H), 4.09 (d, 1H, J = 8.5Hz), 4.12 (m, 1H),

 4.30 (s, 2H), 4.64 (m, 1H), 4.68 (s, 1H), 4.78 (s, 1H), 5.31 (br, 1H), 5.55 (d, 1H, J = 10.0Hz), 5.68 (d , 1H, J = 7.6Hz), 6.19 (m, 1H),

 7.28-7.43 (m, 5H), 7.48 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz),

8.10 (d, 2H, J = 7.5Hz).

MS-FAB: 917 (MH10)

Example 2 7

1 1 2

Replacement form (Rule 26)

Step 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy -4 -Deacetinole-7-deoxy-7 / 3,8S-methylene-4-0-propionyl-19-norbaccatin III

 The compound obtained in Step 2 of Example 23 was reacted in the same manner as in Step 8 of Example 1 to give the title compound as a colorless amorphous solid.

1 1 2/2

Replacement paper (Kaikai IJ26) Ή-NR (CDC1;, / TMS) (5 (ppm):

 -0.32 (s, 3H), -0.14 (s, 3H), 0.73 (s, 9H), 1.22 (s, 6H), 1.24 (s, 9H), 1.36 (t, 1H, J = 7.5Hz), 1.54 (m, 1H), 1.62 (s, 1H), 1.72 (s, 3H),

1.84 (br, 1H), 2.08 (m, 1H), 2.20 (m, 3H), 2.41-2.48 (m, 2H), 2.78 (m, 2H), 2.99 (m, 1H), 3.68 (m, 1H) , 4.08 (d, 1H, J = 8.5Hz), 4.24 (d, 1H, J = 7.6Hz),

4.31 (d, 1H, J: 8.5Hz), 4.47 (s, 1H), 4.72 (s, 1H), 5.03 (d, 1H, J = 10.0Hz), 5.10 (d, 1H, J2 17.1Ηζ), 5.29 (m, 1H), 5.42 (m, 1H), 5.68 (d, 1H, J = 7.6Hz),

5.82 (m, 1H), 6.25 (br, 1H), 7.28-7.40 (m, 5H), 7.48 (t, 2H, J = 7.5Hz), 7.58 (m, 1H), 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 942 (H ⁺ )

Step 2: 13-〇-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-4-deacetyl Nole-7-deoxy-7 / 3, 8 / 3-methylene-10- (2-morpholinoethyl) -4 -〇-propionyl-19-norpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

_{Ή-NR (CDC1 3 / TS} ) (5 (ppm):

 -0.32 (s, 3H), -0.14 (s, 3H), 0.75 (s, 9H), 1.20 (s, 3H), 1.3 (s, 3H), 1.26 (s, 9H), 1.36 (t, 1H, J = 7.5Hz), 1.49 (m, 1H), 1.54 (m, 1H),

1.80 (s, 3H), 1.84 (br, 1H), 2.09-2.20 (m, 4H), 2.30-2.56 (m, 9H),

2.78 (m, 2H), 3.70 (s, 4H), 3.72 (m, 1H), 4.08 (d, 1H, J = 8.5Hz),

 4.26 (d, 1H, J = 7.6Hz), 4.31 (d, 1H, J = 8.5Hz), 4.47 (s, 1H), 4.72 (s, 1H),

5.26 (m, 1H), 5.41 (m, 1H), 5.61 (d, 1H, J = 7.6Hz), 6.22 (m, 1H),

7.28-7.40 (m, 5H), 7.48 (t, 2H, J = 7.5Hz), 7.58 (t, 1H, J = 7.5Hz),

8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 1015 (MH ⁺ )

Step 3: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-4-deacetyl-7-dequin-7 / 3, 8 / 3-Methylene-10- (2-morpholinole) -4-0-propionyl-19-norpaccatin 1Π

1 1 3 The compound obtained in the above Step 2 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 120-125 ° C

Ή-NR (CDC / TMS) 5 (ppm):

 1.20 (s, 3H), 1.23 (s, 3H), 1.25 (m, 3H), 1.26 (s, 9H), 1.49 (m, 1H),

1.54 (m, 1H), 1.78 (s, 3H), 1.87 (s, 1H), 2.09-2.20 (m, 4H),

 2.30-2.59 (m, 9H), 2.68 (m, 2H), 3.70 (m, 4H), 3.72 (m, 1H),

 4.05 (d, 1H, J = 8.5Hz), 4.22 (d, 1H, J = 7.6Hz), 4.31 (d, 1H, J = 8.5Hz),

 4.60 (s, lH), 4.70 (s, 1H), 5.26 (m, 1H), 5.64 (d, 1H, J = 7.6Hz),

 6.22 (m, 1H), 7.31-7.39 (m, 5H), 7.50 (t, 2H, J = 7.5Hz),

 7.60 (t, 1H, J = 7.5Hz), 8.17 (d, 2H, J = 7.5Hz).

MS-FAB: 901 (MH ⁺ )

Example 28

1 1 4

Replacement form (Rule 26)

Replacement form (Rule 26) Step 1: 10-aryl-4-0-butanoyl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylanilamino) -2- (tert-butyldimethylsilyl) oxy-3-phenyl Propionyl] -10-deacetoxy-4-deacetyl-7-deoxy-7 / 3,83-methylene-19-norbaccatine III

 The compound obtained in Step 2 of Example 24 was reacted in the same manner as in Step 8 of Example 1 to give the title compound as a colorless amorphous solid.

_{Ή-NR (CDC1 3 / TMS} ) (5 (ppm):

1 1 4/2

Replacement form (Rule 26) -0.32 (s, 3H), -0.12 (s, 3H), 0.73 (s, 9H), 1.04 (t, 3H, J = 7.5Hz), 1.22 (s, 6H), 1.26 (s, 12H), 1.55 (m, 1H), 1.58 (m, 1H), 1.72 (s, 3H), 1.78-1.92 (m, 3H), 2.10-2.25 (m, 4H), 2.41-2.49 (m, 2H), 2.64 (m , 1H), 2.80 (m, 1H), 2.99 (m, 1H), 3.69 (t, 1H, J = 6.7Hz), 4.08 (d, 1H, J = 8.5Hz),

4.29 (d, 1H, J = 7.6Hz), 4.31 (d, 1H, J = 8.5Hz), 4.48 (s, 1H), 4.72 (s, 1H),

5.03 (d, 1H, J = 10.0Hz), 5.10 (d, 1H, J = 17.1Hz), 5.29 (m, 1H), 5.42 (m, 1H), 5.65 (d, 1H, J = 7.6Hz), 5.82 (m, 1H), 6.23 (m, 1H), 7.28-7.40 (m, 5H),

 7.48 (t, 2H, J = 7.5Hz), 7.58 (t, 1H, J = 7.5Hz), 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 956 (MH ⁺ )

Step 2: 4-O-butanoyl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10 -Deacetoxy-4-deacetinole-7-Dethoxy-7 8 -Methylene-10- (2-morpholinoethyl) -19-Norbaccatin 111

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) 5 (ppm):

 -0.32 (s, 3H), -0.12 (s, 3H), 0.73 (s, 9H), 1.06 (t, 3H, J = 7.5Hz),

 1.20 (s, 3H), 1.23 (s, 3H), 1.27 (s, 9H), 1.48 (m, 1H), 1.56 (m, 1H),

 1.80 (s, 3H), 1.82-1.98 (m, 3H), 2.08-2.23 (m, 4H), 2.30-2.58 (m, 9H),

2.68 (m, 1H), 2.80 (m, 1H), 3.69 (s, 4H), 3.75 (m, 1H),

 4.09 (d, 1H, J = 8.5Hz), 4.29 (d, 1H, J = 7.6Hz), 4.31 (d, 1H, J = 8.5Hz),

 4.48 (s, 1H), 4.72 (d, 1H, J = 4.0Hz), 5.29 (m, 1H), 5.41 (d, 1H, J = 8.6Hz),

5.66 (d, 1H, J = 7.6Hz), 6.21 (m, 1H), 7.28-7.40 (m, 5H),

 7.48 (t, 2H, J = 7.5Hz), 7.58 (t, 1H, J = 7.5Hz), 8.15 (d, 2H, J = 7.5Hz).

MS-FAB: 1029 (H ⁺ )

Step 3: 4-0-butanoyl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-4 -Deacetyl-7-doxy-7 / 3,8 ^ -methylene-10- (2-morpholinoethyl) -19-norbaccatin 1 II The compound obtained in the above Step 2 is reacted in the same manner as in Step 9 of Example 1. To give the title compound

1 1 5 Obtained as a colorless solid.

Melting point: 115-120 ° C

¹ H-NMR (CDCh / TMS) (5 (ppm):

 0.93 (m, 3H), 1.20 (s, 3H), 1.21 (s, 3H), 1.28 (s, 9H), 1.46 (m, IH), 1.55 (m, 1H), 1.64-1.75 (m, 2H) , 1.76 (s, 3H), 1.88 (br, 1H),

2.10-2.22 (m, 4H), 2.30-2.60 (m, 9H), 2.65 (m, 2H), 3.70 (s, 4H),

3.72 (m, 1H), 4.05 (d, 1H, J = 8.5Hz), 4.26 (d, IH, J = 7.6Hz),

 4.29 (d, 1H, J = 8.5Hz), 4.60 (s, IH), 4.70 (s, 1H), 4.76 (br, IH),

4.79 (br, IH), 5.64 (d, IH, J = 7.6Hz), 6.19 (m, IH), 7.28-7.40 (m, 5H), 7.50 (t, 2H, J = 7.5Hz), 7.60 (t , IH, J = 7.5Hz), 8.17 (d, 2H, J = 7.5Hz). MS-FAB: 915 (MH ⁺ )

Example 29

1 1 6

Replacement form (Rule 26)

 HO OBz OAc DMSO OBz OAc

DMSO OBz OH DMSO OBz o 0 HO OBz o 0

116/2 Replacement Paper (Rule 26) Step 1: 10-deacetoxy-7-deokin-7yS, 8-methylene-10- (2-morpholinoethyl) -13-0-triethylsilyl-19-norpaccatin III

 The compound obtained in Step 1 of Example 19 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDCh / TMS) <5 (ppm):

 0.66 (6H, q, J = 7.8Hz), 1.01 (9H, t, J = 7.8Hz), 1.12 (3H, s), 1.15 (3H, s), 1.25-1.56 (3H, m), 1.77 (1H , s), 1.89 (3H, d, J = 1.0Hz), 2.27 (3H, s), 2.04-2.63 (12H, m), 3.71 (4H, m), 4.16 (2H, ABq, J = 8.3Hz) ,

1 1 6/3

Replacement forms (Rule 26) 4.29 (1H, d, J = 8.8Hz), 4.53 (1H, d, J = 3.9Hz), 4.87 (1H, t, J = 7.3Hz),

 7.47 (2H, t, J = 7.8Hz), 7.60 (1H, t, J = 7.3Hz), 8.11 (2H, d, J = 6.8Hz).

Step 2: 10-Deacetoxy-7-deokin-1-0-dimethylsilyl-73,89-methylene

-10- (2-morpholinoethyl) -13- 0-triethylsilyl-19-norpaccatin III The compound obtained in the above Step 1 is reacted in the same manner as in Step 1 of Example 2 to give the title compound as a colorless amorphous solid Obtained.

 Ή-NMR (CDCh / TS) 5 (ppm):

 -0.22 (d, 3H, J = 2.7Hz), 1.10 (d, 3H, J = 2.7Hz), 0.69 (m, 6H),

1.27 (t, 9H, J = 7.5Hz), 1.09 (s, 3H), 1.18 (s, 3H), 1.26 (m, 1H),

1.49 (m, 2H), 1.89 (s, 3H), 2.05 (d, 1H, J = 15.9Hz), 2.19 (m, 1H),

 2.28 (s, 3H), 2.35 (m, 4H), 2.46 (m, 6H), 2.53 (m, 1H), 3.68 (m, 1H),

 3.71 (m, 4H), 4.12 (d, 1H, J = 8.5Hz), 4.24 (m, 2H), 4.53 (m, 1H),

 4.75 (d, 1H, J = 4.0Hz), 4.91 (t, 1H, J = 8.0Hz), 5.69 (d, 1H, J = 7.8Hz),

7.45 (t, 2H, J = 7.5Hz), 7.57 (t, 1H, J = 7.5Hz), 8.10 (m, 2H).

MS-FAB: 796 (MH ⁺ )

Step 3: 10-deacetoquin-4-deacetyl-7-deoxy-1-0-dimethylsilyl-7 / 3, 8 / 3-methylene-10- (2-morpholinoethyl) -13-0-triethylsilyl- 19-Norbach III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 2 of Example 2 to obtain the title compound as a colorless amorphous solid.

'H- 删 R (CDCh / TMS) 5 (ppm):

 -0.24 (d, 3H, J: 2.7 Hz), 0.11 (d, 3H, J = 2.7 Hz), 0.78 (m, 6H), 1.03 (s, 3H),

1.08 (t, 9H, J = 7.5Hz), 1.18 (s, 3H), 1.55 (m, 1H), 1.90 (s, 3H),

 2.15 (m, 3H), 2.35-2.50 (m, 7H), 2.55 (m, 3H),

 2.68 (dd, 1H, J = 2.9Hz, 15.3Hz), 3.49 (s, 1H), 3.70 (m, 5H),

 4.00 (d, 1H, J 7.2Hz), 4.12 (d, 1H, J = 7.5Hz), 4.17 (d, 1H, J = 7.5Hz),

 4.57 (m, 1H), 4.68 (m, 1H), 5.77 (d, 1H, J = 7.2Hz), 7.46 (t, 2H, J = 7.5Hz),

7.58 (t, 1H, J = 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 754 (MH ⁺ )

1 1 7 Step 4: 10-Deacetoxy-4-deacetyl-7-deoxy-1-0-dimethylsilyl-7 / 3,8S-methylene-10- (2-morpholinoethyl) -4-〇-propionyl -13-0 -Triethylsilyl- 19-norpaccatin III

 The compound obtained in the above step 3 was reacted in the same manner as in the step 3 of Example 2 except that cyclopropanecarbonyl chloride was replaced with propionyl chloride to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDC / TMS) 5 (ppm):

 -0.24 (d, 3H, J = 2.7Hz), 0.11 (d, 3H, J = 2.7Hz), 0.69 (m, 6H),

 1.02 (t, 9H, J = 7.5Hz), 1.09 (s, 3H), 1.18 (s, 3H), 1.24 (t, 3H, J = 7.5Hz),

1.48 (m, 2H), 2.07 (d, 1H, J = 15.8Hz), 2.17 (m, 1H), 2.34 (m, 3H),

 2.46 (m, 7H), 2.54 (m, 1H), 2.62 (m, 2H), 2.67 (m, 1H),

 3.68 (t, 1H, J = 6.0Hz), 3.72 (m, 4H), 4.13 (d, 1H, J = 8.3Hz),

 4.21 (d, 1H, J = 7.7Hz), 4.24 (d, 1H, J = 8.3Hz), 4.52 (m, 1H),

 4.71 (d, 1H, J = 4.0Hz), 4.91 (t, 1H, J = 8.2Hz), 5.69 (d, 1H, J = 7.7Hz),

7.46 (t, 2H, J = 7.5Hz), 7.58 (t, 1H, J = 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 810 (MH ⁺ )

Step 5: 10-Deacetoxy-4-deacetyl-7-deoxy-7 / 3, 8 / 3-methylene-10- (2-morpholinoethyl) -4-0-propionyl-19-norpaccatin II I

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

'Η-Koku R (CDCh / TMS) 5 (ppm):

 1.07 (s, 3H), 1.15 (s, 3H), 1.1 (t, 3H, J = 7.5Hz), 1.52 (m, 1H), 1.92 (s, 3H), 2.10 (d, 1H, J = 15.8Hz), 2.22 (m, 2H), 2.32-2.70 (m, 13H), 3.70 (m, 5H), 4.03 (d, 1H, J = 8.5Hz), 4.30 (d, 1H, J = 8.5Hz) , 4.37 (d, 1H, J = 7.8Hz),

4.71 (d, 1H, J = 3.9Hz), 4.81 (d, 1H, J = 7.5Hz), 5.61 (d, 1H, J = 7.8Hz),

7.48 (t, 2H, J = 7.5Hz), 7.61 (t, 1H, J = 7.5Hz), 8.14 (m, 2H).

MS-FAB: 637 (MH ⁺ )

Step 6: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10 deacetoxy-4-decetyl-7- Deoxy-7

1 1 8 3,83-methylene-10- (2-morpholinoethyl) -4-0-propionyl-19-norpaccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 5 of Example 10 and then reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 135-140 ° C

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.14 (s, 9H), 1.21 (s, 3H), 1.26 (s, 3H), 1.33 (s, 3H),

 1.44 (t, 3H, J = 7.5Hz), 1.57 (m, 1H), 1.72 (s, 3H), 2.13 (d, 1H, J = 15.6Hz),

2.18 (m, 2H), 2.30-2.49 (m, 10H), 2.57 (m, 1H), 2.77 (m, 1H), 2.94 (m, 1H),

3.70 (m, 4H), 3.72 (m, 1H), 4.08 (d, 1H, J = 8.3Hz), 4.23 (d, 1H, J = 7.6Hz),

4.33 (d, 1H, J = 8.3Hz), 4.72 (m, 1H), 4.99 (d, 1H, J = 9.9Hz),

 5.49 (d, 1H, J = 9.9Hz), 5.67 (d, 1H, J = 7.6Hz), 6.31 (m, 1H),

7.33-7.40 (m, 5H), 7.50 (t, 2H, J = 7.5Hz), 7.58 (t, 1H, J = 7.5Hz),

 8.19 (d, 2H, J = 7.5Hz).

MS-FAB: 915 (MH ⁺ )

Example 30

1 1 9

Replacement form (Rule 26)

Replacement form (Rule 26) Step 1: 10-aryl-10-deacetoxy-4-deacetyl-4-0-propionyl-13-0-triethylsilinole-7-0-trifluoromethanesulfonylbaccatin

 The compound obtained in Step 7 of Example 6 was reacted in the same manner as in Step 5 of Example 1 to obtain the title compound as a colorless amorphous solid.

1 1 9/3

Replacement paper (Kaikai IJ26) _{Ή-NMR (CDC1 3 / TMS} ) 5 (ppm):

 0.65 (m, 6H), 0.99 (m, 9H), 1.13 (s, 3H), 1.10 (s, 3H), 1.13 (s, 3H),

1.28 (t, 3H, J 2 7.5Hz), 1.80 (s, 3H), 1.88 (s, 3H), 2.08 (m, 1H),

 2.20 (m, 2H), 2.42 (m, 1H), 2.62 (m, 2H), 2.80 (m, 2H), 4.10 (m, 2H),

4.18 (d, 1H, J = 8.3Hz), 4.30 (d, 1H, J = 8.3Hz), 4.90 (m, 2H),

 5.00 (d, 1H, J-10.0Hz), 5.08 (d, 1H, J = 17.0Hz),

 5.60 (dd, 1H, J = 7.3Hz, 10.7Hz), 5.65 (d, 1H, J = 7.4Hz), 5.75 (m, 1H),

 7.46 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz), 8.09 (d, 2H, J = 7.5Hz).

Step 2: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-7 / 3,8 / 3-methylen-4-0-propionyl-13-0-triethylsilyl-19-norpaccatin III In step 1 above The obtained compound was reacted in the same manner as in Step 3 of Example 18 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) <5 (ppm):

 0.65 (m, 6H), 1.00 (t, 9H, J = 7.8Hz), 1.13 (s, 3H), 1.15 (s, 3H),

1.23 (t, 3H, J = 7.4Hz), 1.50 (m, 1H), 1.80 (s, 3H), 2.08-2.21 (m, 5H),

2.28 (dd, 1H, J = 8.8Hz, 15.lHz), 2.46 (dt, 1H, J = 4.4Hz, 15.6Hz),

2.60 (m, 2H), 2.96 (m, 1H), 3.69 (m, 1H), 4.06 (d, 1H, J = 8.5Hz),

4.21 (d, 1H, J = 7.8Hz), 4.29 (d, 1H, J = 8.5Hz), 4.70 (d, 1H, J = 3.9Hz),

 4.88 (t, 1H, J = 8.0Hz), 4.99 (d, 1H, J = 9.7Hz), 5.08 (dd, 1H, J: 2.0Hz, 17.lHz),

5.57 (d, 1H, J = 7.8Hz), 5.80 (m, 1H), 7.46 (t, 2H, J = 7.5Hz),

7.60 (t, 1H, J = 7.5Hz), 8.11 (d, 2H, J = 7.5Hz).

 MS-FAB: 678 (ΜΗ ')

Step 3: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-7 / 3,8 / 3-methylene-4-〇-propionyl-19-norpaccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 1.09 (s, 3H), 1.15 (s, 3H), 1.26 (t, 3H, J = 7.4Hz), 1.50 (m, 1H),

1.86 (s, 3H), 2.08 (d, 1H, J = 16.1Hz), 2.21 (m, 3H),

1 2 0 2.31 (dd, lH, J = 7.3Hz, 15.6Hz), 2.46 (dt, 1H, J = 4.4Hz, 16.1Hz), 2.68 (m, 1H),

2.72 (m, 1H), 2.99 (m, 1H), 3.70 (dd, 1H, J = 6.2Hz, 7.5Hz),

 4.05 (d, 1H, J = 8.5Hz), 4.31 (d, 1H, J: 8.5Hz), 4.35 (d, 1H, J = 7.2Hz),

4.70 (d, 1H, J = 3.9Hz), 4.82 (br, 1H), 4.99 (d, 1H, J = 9.7Hz),

 5.08 (d, 1H, J = 17.lHz), 5.60 (d, 1H, J = 7.2Hz), 5.83 (m, 1H),

 7.46 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz), 8.14 (d, 2H, J = 7.5Hz).

MS-FAB: 564 (MH ⁺ )

Step 4: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4 -Decetyl-7-dexoxy-7 / 3,8-methylene-4-0-propionyl-19-norpaccatin III The compound obtained in the above step 3 and the compound obtained in the step 2 of the reference example 3 were subjected to the steps of the example 10. After reacting in the same manner as in 5, the resulting 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy- 2-methyl-3-phenylpropionyl] -10-deacetoxy-4-deacetyl-7-deoxy-7 / 3,8; 3-methylen-4-0-propionyl-19-norbaccatin II I and 10-aryl- 13-〇- (tert-Butoxycarbonyl) -10-deacetoxy-4-deacetyl-7-deoxy-73,8-methylen-4-0 propionyl-19-norpaccatin III Rahi Dorofuran was dissolved in 5 ml, tetra - n-Petit Ruan monitor © beam Full O Li de (1 M Tetorahi Dorofura down solution) 345 ml, and reacted for 10 minutes at the same temperature was added at 0 ° C. The reaction solution was diluted with ethyl acetate, washed with a saturated aqueous solution of ammonium chloride and saturated saline in that order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; ethyl acetate: hexane = 3: 7 (v / v)) to obtain the title compound 50 as a colorless amorphous solid.

Ή-NMR (CDC1:, / TMS) (5 (ppm):

 1.12 (s, 9H), 1.23 (s, 3H), 1.32 (s, 3H), 1.43 (t, 3H, J-7.3Hz),

1.58 (m, 1H), 1.65 (s, 3H), 2.12 (d, 1H, J = 15.9Hz), 2.17 (m, 2H),

2.42 (m, 3H), 2.73 (m, 1H), 2.98 (m, 2H), 3.59 (br, 1H), 3.68 (m, 1H), 4.05 (d, 1H, J = 8.5Hz), 4.21 (d , 1H, J = 7.8Hz), 4.32 (d, 1H, J = 8.5Hz),

4.70 (d, 1H, J = 3.9Hz), 4.98 (m, 2H), 5.06 (d, 1H, J = 17.1Hz),

1 2 1 5.50 (d, 1H, J = 9.8 Hz), 5.62 (d, 1H, J = 7.8 Hz), 5.78 On, 1H),

 6.31 (m, 1H), 7.33 (m, 5H), 7.49 (t, 2H, J = 7.5 Hz), 7.58 (t, 1H, J 7.5 Hz), 8.19 (d, 2H, J = 7.5Hz).

MS-FAB: 842 (MH ⁺ )

Step 5: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4-decetyl-7 -Doxy-7 / 3,8 / 3-Methylene-10- (2-morpholinole) -4-0-propionyl-19-Norbach tin m

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound (the compound obtained in Step 6 of Example 29) as a colorless solid.

Example 3 1

1 2 2

Replacement form (Rule 26)

t

Step 1: 10-Deacetoxy-7-deoxy-7,8 / 3-methylene-10- (2-morpholinoethylene) -19-norpaccatin

 Example 29 The compound obtained in Step 1 of 9 was reacted in the same manner as in Step 7 of Example 1 to give the title compound as a colorless amorphous solid.

Ή-N R (CDCh / TMS) (5 (ppm):

 1.09 (s, 3H), 1.11 (s, 3H), 1.52 (m, 1H), 1.92 (s, 3H), 2.00-2.10 (m, 2H),

2.18 (m, 1H), 2.23 (m, 1H), 2.30-2.60 (m, 10H), 3.68 (m, 4H), 3.71 (m, 1H),

4.02 (d, 1H, J = 8.3Hz), 4.28 (d, 1H, J = 7.6Hz), 4.36 (d, 1H, J = 8.3Hz),

 4.71 (m, lH), 4.80 (t, 1H, J = 7.5Hz), 5.60 (d, 1H, J = 7.6Hz),

 7.49 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz), 8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 623 (MH ⁺ )

1 2 2/2

Replacement form (Rule 26) Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-7-deokin-7 / 3,8-Methylen-10- (2-morpholinoethyl) -19-norpaccatin ΙΠ

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 5 of Example 10 and then reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 140-145 ° C

Ή-NMR (CDCh / TMS) <5 (ppm):

 1.10 (s, 9H), 1.19 (s, 3H), 1.21 (s, 3H), 1.30 (s, 3H), 1.59 (m, 1H),

1.70 (s, 3H), 2.10 (d, 1H, J = 15.6Hz), 2.17 (m, 2H), 2.30-2.45 (m, 10H), 2.57 (m, 2H), 2.60 (s, 3H), 2.30 -2.45 (m, 10H), 3.65 (m, 4H), 3.70 (m, 1H), 4.02 (d, 1H, J = 8.3Hz), 4.26 (d, 1H, J-7.6Hz), 4.30 (d, 1H, J = 8.3Hz),

 4.76 (m, 1H), 5.00 (d, 1H, J = 9.9Hz), 5.49 (d, 1H, J = 9.9Hz),

 5.63 (d, 1H, J = 7.6Hz), 6.31 (m, 1H), 7.31 (m, 5H), 7.49 (t, 2H, J = 7.5Hz), 7.53 (t, 1H, J2 7.5Hz), 8.16 (d, 2H, J = 7.5Hz).

MS-FAB: 901 (MH ⁺ )

Example 32

one two Three

Replacement paper (Kaikai IJ26)

Step 1: 10-Deacetoxy-4-deacetyl-7-deoxy-1-0-dimethylsilyl-4-0-ethoxycarbonyl-7 / 3,8 ^ -methylene-10- (2-morpholinoethyl) -13- 0-Triethylsilyl-19-norpaccatin Π I

 1 2 3/2

Replacement form (Rule 26) The compound obtained in Step 3 of Example 29 was reacted in the same manner as in Step 3 of Example 9 to obtain the title compound as a colorless amorphous solid.

 1 H-NMR (CDCh / TMS) 5 (ppm):

 -0.24 (d, 3H, J = 2.7Hz), 0.11 (d, 3H, J = 2.7Hz), 0.69 (m, 6H),

 1.02 (t, 9H, J = 7.5Hz), 1.09 (s, 3H), 1.18 (s, 3H), 1.40 (t, 3H, J = 7.2Hz), 1.50 (m, lH), 1.72 (br, 1H ), 1.90 (s, 3H), 2.10 (d, 1H, J2 15.8Hz),

2.17 (m, lH), 2.30-2.60 (m, 12H), 3.68 (t, 1H, J2 4.5Hz), 3.72 (m, 4H), 4.13 (m, 1H), 4.24 (d, 1H, J = 8.5Hz), 4.29 (d, 1H, J: 7.7Hz), 4.40 (m, 1H),

4.53 (m, 1H), 4.75 (d, 1H, J = 4.0Hz), 4.91 (t, 1H, J: 8.0Hz),

 5.69 (d, 1H, J = 7.7Hz), 7.46 (t, 2H, J = 7.5Hz), 7.58 (t, 1H, J = 7.5Hz),

8.12 (d, 2H, J = 7.5Hz).

MS-FAB: 826 (MH ⁺ )

Step 2: 10-Deacetoxy-4-deacetyl-7-deoxy-4-0-ethoxycarbonyl -73,83-methylene-10- (2-morpholinoethyl) -19-norbaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TMS} ) 5 (ppm):

 1.06 (s, 3H), 1.15 (s, 3H), 1.38 (t, 3H, J = 7.3Hz), 1.50 (m, 2H),

 1.94 (s, 3H), 2.12 (d, 1H, J = 15.6H2), 2.19 (m, 1H), 2.28-2.55 (m, 12H),

3.71 (m, 4H), 3.76 (m, 1H), 4.03 (d, 1H, J = 8.7Hz), 4.20 (m, 1H),

 4.30 (m, 2H), 4.41 (d, 1H, J2 7.8Hz), 4.79 (m, 2H), 5.61 (d, 1H, J = 7.8Hz), 7.49 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz), 8.14 (m, 2H).

Step 3: 13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4-decetyl-7 -Deoxy-4-0-ethoxycarbonyl-7,83-methylene-10- (2-morpholinoethyl) -19-norbaccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 5 of Example 10 and then reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 130-135 ° C

1 2 4 Ή-NMR (CDCl _a / TS) (5 (ppm):

 1.20 (s, 3H), 1.21 (s, 3H), 1.26 (s, 3H), 1.27 (s, 9H), 1.39 (m, 3H),

1.48 (m, lH), 1.52 (m, IH), 1.70 (s, 3H), 2.13 (d, IH, J = 16.1Hz),

 2.20-2.48 (m, 12H), 2.53 (m, 1H), 3.69 (m, 4H), 3.72 (m, IH), 4.09 (m, IH),

4.12 (m, lH), 4.29 (d, IH, J = 6.9Hz), 4.35 (d, IH, J = 8.8Hz), 4.43 (m, IH),

4.79 (s, lH), 5.04 (d, 1H, J = 9.9Hz), 5.65 (d, 1H, J = 10.3Hz),

 5.67 (d, IH, J = 6.9Hz), 6.11 (br, IH), 7.29-7.40 (m, 5H),

 7.47 (t, 2H, J = 7.5Hz), 7.58 (t, 1H, J = 7.5Hz), 8.14 (d, 2H, J = 7.5Hz).

 MS-FAB: 931 (MH10)

Example 3 3

1 2 5

Replacement forms (Rule 26)

125/1 Replacement Form (Rule 26) 10-aryl-13-〇-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-7-dequin-7 / S , Methylene-19-norpaccatin III

 The compound obtained in Step 5 of Example 18 was reacted in the same manner as in Step 9 of Example 1 to give the title compound as a colorless solid.

Melting point: 130-135 ° C

1 H-NR (CDC / TMS) (5 (ppm):

 1.24 (s, 3H), 1.26 (s, 3H), 1.27 (s, 9H), 1.55 (m, 1H), 1.71 (s, 3H),

 2.08 (d, 1H, J2 16.1Hz), 2.20 (m, 2H), 2.38 (s, 3H), 2.40 (m, 2H),

 2.99 (m, 1H), 3.30 (br, 1H), 3.69 (dd, 1H, J = 6.0Hz, 8.0Hz),

 4.03 (d, 1H, J = 8.5Hz), 4.21 (d, 1H, J = 7.8Hz), 4.29 (d, 1H, J = 8.5Hz),

 4.59 (s, lH), 4.73 (d, 1H, J = 3.5Hz), 5.00 (d, 1H, J = 10.0Hz),

 5.12 (d, 1H, J = 17.0Hz), 5.28 (m, 1H), 5.38 (d, 1H, J = 9.0Hz),

 5.65 (d, 1H, J = 6.8Hz), 5.80 (m, 1H), 6.25 (m, 1H), 7.28-7.36 (m, 5H),

1 2 5/2

Replacement form (Rule 26) 7.48 (t, 2H. J = 7.5Hz). 7.58 (t, 1H, J = 7.5Hz), 8.12 (d, 2H, J = 5Hz). MS-FAB: 813 (MHO

Example 34

i wH dimension

Replacement form (Rule 26)

126/2 Replacement Paper (Rule 26) Step 1: 10-aryl-10-deacetoxy-4-deacetyl-4-0-propionyl-13-0- (2,2,2-trichloromouth ethoxyquincarbonyl) -7-0-triethylsilyl paccatin III 400 mg of the compound obtained in Step 2 of Example 7 was reacted in the same manner as in Step 1 of Example 23 to introduce a propionyl group at the 4-position. The obtained compound was reacted in the same manner as in Step 4 of Example 2 and purified by silica gel thin-layer chromatography (developing solvent; chloroform: methanol = 95: 5 (v / v)) to give 10-aryl- 10-Deacetoxy-4-deacetyl-4-0-propionylbaccatin III was obtained. This was dissolved in 6 ml of dried N, N-dimethylformamide, 140 mg of imidazole and 0.345 ml of triethylsilane chloride were added at 0 ° C, and reacted at the same temperature for 60 minutes. The reaction mixture was diluted with ethyl acetate, washed with a saturated aqueous solution of ammonium chloride and saturated saline in that order, and dried over anhydrous magnesium sulfate.

1 2 6/3

Replacement form (Rule 26) The solvent was distilled off. The obtained residue was dissolved in 12 ml of dried pyridine, 0.345 ml of 2,2,2-trichloromethyl chloroformate was added, and the mixture was stirred at 60 ° C. for 1 hour. 0. The mixture was diluted with ethyl acetate, washed with a saturated aqueous solution of ammonium chloride and saturated saline in this order, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (elution solvent; hexane: ethyl acetate = 8: 2 (v / v)) to obtain 372 mg of the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 0.57 (m, 6H), 0.97 (t, 9H, J = 7.5Hz), 1.16 (s, 6H), 1.31 (t, 3H, J = 7.5Hz), 1.62 (s, 3H), 1.85 (s, 3H ), 1.89 (m, 1H), 2.31 (m, 1H), 2.37 (m, 1H),

2.50 (m, 2H), 2.70 (m, 2H), 2.81 (m, 1H), 3.91 (dd, 1H, J = 4.3Hz, 10.4Hz),

4.01 (d, 1H, J-7.1Hz), 4.18 (d, 1H, J = 8.5Hz), 4.30 (d, 1H, J = 8.5Hz),

4.58 (dd, 1H, J = 6.5Hz, 10.7Hz), 4.85 (AB type d, 2H, J = ll.9Hz),

4.91 (dd, 1H, J = 2.0Hz, 9.5Hz), 5.02 (dd, 1H, J = l.6Hz, 9.9Hz),

 5.10 (dd, 1H, J = 1.6Hz, 16.9Hz), 5.63 (d, 1H, J = 7.2Hz), 5.77 (m, 1H),

 5.98 (m, 1H), 7.47 (t, 2H, J = 7.5Hz), 7.61 (t, 1H, J = 7.5Hz),

8.10 (d, 2H, J = 7.5Hz).

MS-FAB: 871 (MH ⁺ )

Step 2: 10-Deacetoxy-4-deacetyl-10- (2-hydroxyshethyl) -4-0-propionyl-13-0_ (2,2,2-trichloroethoxycarbonyl) -7-0-d Lietylsilyl paccatin III

 11.4 g of the compound obtained in the above step 1 was dissolved in a mixed solvent of 150 ml of tetrahydrofuran, 100 ml of methanol and 50 ml of water, and 7.67 g of N-methylmorpholine-N-oxide was added to an aqueous solution of osmium tetroxide (0.1 (M solution) was added and stirred at room temperature for 15 hours. The reaction solution was diluted with ethyl acetate, washed with an aqueous solution of sodium thiosulfate, 1N hydrochloric acid and saturated saline in this order, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was dissolved in a mixed solvent of 100 ml of tetrahydrofuran, 100 ml of methanol and 100 ml of water, and sodium metaperiodate 14 was added, followed by stirring at room temperature for 3 hours. The reaction solution was diluted with ethyl acetate, washed with water, a saturated aqueous solution of sodium bicarbonate and saturated saline in this order, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue obtained was dried

1 2 7 Dissolve in 230 ml of methanol, add 495 mg of sodium borohydride at 0 ° C, stir at the same temperature for 30 minutes, and add 495 ml of sodium borohydride at 0 ° C, and add 30 ml at the same temperature. Stirred for minutes. The reaction solution was diluted with ethyl acetate and poured into a cold saturated aqueous ammonium chloride solution. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (elution solvent; hexane: ethyl acetate = 8: 2 (vΛ)) to obtain 7.91 g of the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TS) (5 (ppm):

 0.60 (m, 6H), 0.99 (s, 9H), 1.14 (s, 6H), 1.32 (m, 3H), 1.65 (s, 3H),

1.90 (m, 3H), 1.95 (s, 3H), 2.31 (m, 1H), 2.40 (m, 1H), 2.51 (m, 1H),

2.70 (m, 2H), 3.61 (m, 1H), 3.73 (m, 1H), 4.06 (m, 2H),

4.18 (d, 1H, J = 8.5Hz), 4.32 (d, 1H, J = 8.5Hz), 4.59 (dd, 1H, J = 6.5Hz, 10.7Hz),

4.82 (AB type d, 2H, J = 12.0Hz), 4.91 (d, 1H, J = 9.7Hz),

 5.63 (d, 1H, J = 7.3Hz), 5.99 (t, 1H, J = 8.3Hz), 7.47 (t, 2H, J = 7.5Hz),

7.61 (t, 1H, J = 7.5Hz), 8.11 (m, 2H).

MS-FAB: 875 (MH ⁺ )

Step 3: 10-Deacetoxy-4-deacetyl-4-0-propionyl-13-0- (2,2,2-trichloroethoxycarbonyl) -7-〇-triethylsilyl-10-vinylbacca Tin III The compound obtained in the above Step 2 was reacted in the same manner as in Step 4 of Example 6, and then reacted in the same manner as in Step 5 of Example 6. Thus, the title compound was obtained as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TMS} ) (5 (ppm):

 0.56 (m, 6H), 0.94 (t, 9H, J = 7.8Hz), 1.04 (s, 3H), 1.16 (s, 3H),

 1.33 (t, 3H, J = 7.5Hz), 1.65 (s, 3H), 1.90 (d, 3H, J = l.0Hz), 1.91 (m, 1H),

2.32 (m, 1H), 2.38 (m, 1H), 2.49 (m, 1H), 2.71 (m, 2H),

 4.08 (d, 1H, J = 7.3Hz), 4.16 (d, 1H, J = 8.3Hz), 4.32 (d, 1H, J = 8.3Hz),

 .51 (d, 1H, J = 2.5Hz), 4.56 (dd, 1H, J = 6.3Hz, 10.7Hz),

 .86 (AB type d, 2H, J = 12.0Hz), 4.90 (d, 1H, J = 9.0Hz),

 .06 (d, 1H, J = 17.5Hz), 5.25 (m, 1H), 5.63 (d, 1H, J = 7.3Hz),

 .04 (t, 1H, J = 8.0Hz), 6.60 (m, 1H), 7.47 (t, 2H, J = 7.5Hz),

1 2 8 7.61 (t, 1H, J = 7.5Hz), 8.10 (m, 2H).

MS-FAB: 857 (MH ⁺ )

Step 4: 10-Deacetoxy-4-deacetyl-10-formyl-4-0-propionyl-13-0- (2,2,2-trichloroethoxycarbonyl) -7-0-triethylsilylpaccatin III Above 4.5 g of the compound obtained in step 3 was dissolved in a mixed solvent of 80 ml of tetrahydrofuran, 80 ml of methanol and 80 ml of water, and 3.07 g of N-methylmorpholine-N-oxide was added to an aqueous solution of osmium tetroxide (3.0 g). 15.7 ml) was added, and the mixture was stirred at room temperature for 12 hours. The reaction solution was diluted with ethyl acetate, washed with an aqueous solution of sodium thiosulfate, 1N hydrochloric acid, and saturated saline in this order, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was treated with 80 ml of tetrahydrofuran. Was dissolved in a mixed solvent of 80 ml of methanol and 80 ml of water, 5.6 g of sodium metaperiodate was added, and the mixture was stirred at room temperature for 3 hours. The reaction solution was diluted with ethyl acetate, washed with water, a saturated aqueous solution of sodium bicarbonate and saturated saline in this order, dried over anhydrous magnesium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (elution solvent; hexane: ethyl acetate = 9: 1 (v / v)) to obtain 3.09 g of the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 0.60 (m, 6H), 0.96 (s, 3H), 0.97 (m, 9H), 1.05 (s, 3H),

 1.32 (t, 3H, J = 7.5Hz), 1.62 (s, 3H), 1.84 (s, 3H), 1.91 (m, 1H),

 2.32 (m, 2H), 2.52 (m, 1H), 2.70 (m, 2H), 3.48 (m, 1H),

 3.95 (d, 3H, J = 6.8Hz), 4.19 (m, 1H), 4.32 (d, 1H, J = 8.3Hz),

 4.60 (dd, 1H, J = 6.3Hz, 10.5Hz), 4.84 (AB type d, 2H, J = 12.0Hz),

4.90 (m'lH), 5.63 (d, 1H, J = 5.6Hz), 6.04 (t, 1H, J = 8.0Hz),

7.47 (t, 2H, J = 7.5Hz), 7.61 (t, 1H, J = 7.5Hz), 8.10 (m, 2H), 10.23 (s, 1H). MS-FAB: 859 (H ⁺ )

Step 5: 10-Deacetoxy-4-deacetyl-10-morpholinomethyl-4-0-propionyl -13-0- (2,2,2-trichloroethoxycarbonyl) -7-0-Triethylsilylbac Power ΙΠ

 Compound 3.08 obtained in the above Step 4 was dissolved in 308 ml of dried ethanol, and 0.624 ml of morpholine and 0.41 ml of acetic acid were added at -20 ° C. Hydrogenated shear is added to this solution.

1 2 9 Sodium noborate 55 mg was added in four portions at 5 minute intervals. After stirring at −20 ° C. for 25 minutes, 0.936 ml of morpholine and 0.625 ml of acetic acid were added at −20 ° C., and the mixture was stirred at 6 ° C. for 15 hours. 225 mg of sodium hydrogen cyanoborate was further added, and the mixture was reacted at room temperature for 3 hours. The reaction solution was diluted with ethyl acetate at 0 ° C., washed with a saturated aqueous solution of ammonium chloride and saturated saline in this order, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; hexane: ethyl acetate 2.8: 2 (v / v)) to give 1.51 g of the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) (5 (ppm):

 0.60 (m, 6H), 0.97 (t, 9H, J = 7.5Hz), 1.12 (s, 3H), 1.18 (s, 3H),

 1.32 (t, 3H, J = 7.5Hz), 1.62 (s, 3H), 1.88 (m, 1H), 1.98 (s, 3H),

 2.30-2.40 (m, 2H), 2.49 (m, 4H), 2.70 (m, 4H),

 3.15 (dd, 1H, J = 3.5Hz, 13.5Hz), 3.64 (m, 4H), 4.05 (d, 1H, J: 7.3Hz),

 4.08-4.16 (m, 2H), 4.32 (d, 1H, J = 8.3Hz), 4.60 (dd, 1H, J = 6.5Hz, 10.5Hz),

4.84 (AB type d, 2H, J = ll.7Hz), 4.90 (d, 1H, J = 10.0Hz),

 5.61 (d, 1H, J = 6.8Hz), 5.96 (t, 1H, J = 8.0Hz), 7.47 (t, 2H, J = 7.5Hz),

 7.61 (t, 1H, J = 7.5Hz), 8.10 (d, 2H, J = 7.5Hz).

MS-FAB: 930 (MH ⁺ )

Step 6: 10-Deacetoxy-4-deacetyl-10-morpholinomethyl-4-0-propionyl-13-0- (2,2,2-trichloroethoxycarbonyl) paccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) (5 (ppm):

 1.06 (s, 3H), 1.12 (s, 3H), 1.32 (t, 3H, J = 7.5Hz), 1.72 (s, 3H),

1.82 (m, 1H), 1.91 (s, 3H), 2.10 (m, 1H), 2.32 (m, 3H), 2.59 (m, 4H),

2.70 (m, 2H), 3.40 (dd, 1H, J = 8.0Hz, 13.0Hz), 3.61 (m, 4H), 4.00 (m, 2H), 4.19 (d, 1H, J = 8.5Hz), 4.31 ( d, 1H, J = 8.5Hz), 4.49 (m, 1H),

 4.82 (AB type d, 2H, J = ll.7Hz), 4.94 (d, 1H, J = 7.8Hz),

 5.61 (d, 1H, J = 7.3Hz), 5.96 (m, 1H), 7.47 (t, 2H, J = 7.5Hz),

1 3 0 7.61 (t, 1H, J = 7.5Hz), 8.10 (d, 2H, J = 7.5Hz).

Step 7: 10-Deacetoxy-4-deacetyl-10-morpholinomethyl-4-0-propionyl-13-0- (2,2,2-trichloroethoxycarbonyl) -7-0-trifluoromethane Sulfonyl baccatin III

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 5 of Example 1 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDC / TS) (5 (ppm):

 1.12 (s, 3H), 1,19 (s, 3H), 1.31 (t, 3H, J = 7.3Hz), 1.79 (s, 3H),

 1.99 (s, 3H), 2.20 (m, 1H), 2.35 (m, 2H), 2.42 (m, 2H), 2.59 (m, 2H),

2.70 (m, 3H), 2.81 (m, 1H), 3.18 (dd, 1H, J = 4.0Hz, 14.0Hz), 3.62 (m, 4H),

4.19 (m, 2H), 4.27 (dd, 1H, J = 4.3Hz, 8.3Hz), 4.35 (d, 1H, J = 8.3Hz),

 4.86 (AB type d, 2H, J = 12.0Hz), 4.88 (m, 1H), 5.66 (m, 1H),

 5.98 (t, 1H, J = 8.3Hz), 7.49 (t, 2H, J = 7.5Hz), 7.63 (t, 1H, J = 7.5Hz),

 8.08 (d, 2H, J = 7.5Hz).

MS-FAB: 948 (H ⁺ )

Step 8: 10-Deacetoxy-4-deacetyl-7 Deoxy-7 / 3,8 / 3-methylene-10-mol holinomethyl-4-0-propionyl-13-0- (2,2,2-trichloroethoxycarbonyl ) -19-Nolpaccatin III

 The compound obtained in the above Step 7 was reacted in the same manner as in Step 3 of Example 18 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

1.14 (s, 3H), 1.16 (s, 3H), 1.28 (t, 3H, J = 7.3Hz),

1.51 (dd, 1H, J = 5.4Hz, 6.8Hz), 1.91 (s, 311), 1.95 (s, 1H),

2.10 (d, 1H, J: 16.lHz), 2.18 (m, 1H), 2.35-2.50 (m, 8H), 2.60-2.72 (m, 2H), 3.36 (dd, 1H, J = 4.4Hz, 13.2 Hz), 3.64 (m, 4H), 3.80 (t, 1H, J = 5.4Hz),

4.03 (d, 1H, J = 8.3Hz), 4.31 (d, 1H, J = 8.3Hz), 4.35 (d, 1H, J = 7.8Hz),

 4.69 (d, 1H, J = 3.9Hz), 4.82 (d, 1H, J = 12.2Hz), 4.88 (d, 1H, J = 12.2Hz),

 5.60 (d, 1H, J = 7.8Hz), 5.90 (t, 1H, J = 7.8Hz), 7.49 (t, 2H, J = 7.5Hz),

7.63 (t, 1H, J = 7.5Hz), 8.11 (m, 2H).

1 3 1 MS-FAB: 799 (MH ⁺ )

Step 9: 10-Deacetoxy-4-deacetyl-7-deoxy-73,8-methylene-10-mole holinomethyl-4-0-propionyl-19-norpaccatin III

 The compound obtained in the above Step 8 was reacted in the same manner as in Step 4 of Example 1 to obtain the title compound as a colorless amorphous solid.

 Ή-NMR (CDCh / TMS) (5 (ppm):

 1.09 (s, 3H), 1.26 (t, 3H, J = 7.3Hz), 1.52 (m, 1H), 1.80 (s, 1H),

1.96 (s, 3H), 2.10 (d, 1H, J = 16.1Hz), 2.22 (m, 2H), 2.32 (m, 2H),

2.45-2.70 (m, 7H), 3.32 (dd, 1H, J = 4.9Hz, 12.7Hz), 3.65 (m, 4H),

 3.80 (m, 1H), 4.05 (d, 1H, J = 8.8Hz), 4.30 (d, 1H, J = 8.8Hz),

 4.38 (d, 1H, J = 7.8Hz), 4.71 (s, 1H), 4.79 (br, 1H), 5.59 (d, 1H, J = 7.8Hz), 7.49 (t, 2H, J = 7.5Hz), 7.61 (t, 1H, J = 7.5Hz), 8.14 (d, 2H, J = 7.5Hz).

MS-FAB: 623 (MH ⁺ )

Step 10: 13-〇-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy- 4-Decetyl-7-deoxy-7 / 3,8 / 3-methylene-10-morpholinomethyl-4- 4-propionyl-19-norpaccatin III

 The compound obtained in the above Step 9 was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDC / TMS) (5 (ppm):

 -0.31 (s, 3H), -0.13 (s, 3H), 0.75 (s, 9H), 1.18 (s, 3H), 1.26 (s, 3H),

1.28 (s, 9H), 1.37 (t, 3H, J = 7.5Hz), 1.54 (m, 1H), 1.81 (s, 3H),

 1.92 (br, 1H), 2.14 (d, 1H, J = 16.1Hz), 2.18 (m, 2H),

 2.36 (dd, 1H, J = 5.0Hz, 13.1Hz), 2.46 (m, 2H), 2.53 (m, 4H), 2.79 (m, 2H),

3.37 (dd, 1H, J = 5.2Hz, 13.1Hz), 3.66 (m, 4H), 3.78 (m, 1H),

 4.07 (d, 1H, J = 8.5Hz), 4.28 (d, 1H, J = 7.8Hz), 4.34 (d, 1H, J = 8.5Hz),

 4.48 (s, lH), 4.72 (d, 1H, J = 3.9Hz), 5.26 (br, 1H), 5.47 (d, 1H, J = 9.3Hz),

5.66 (d, 1H, J = 7.8Hz), 6.24 (t, 1H, J = 8.8Hz), 7.29-7.40 (m, 5H),

 7.49 (t, 2H, J = 7.5Hz), 7.58 (t, 1H, J = 7.5Hz), 8.15 (d, 2H, J = 7.5Hz).

1 3 2 MS-FAB: 1001 (MH ⁺ )

Step 11 1: 13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroquin-3--3-phenylpropionyl] -10-deacetoxy-4-deacetyl-7-deoxy- 7/5, 8 / 3-Methylene-10-morpholinomethyl-4-0-propionyl-19-norbaccatin 化合物 The compound obtained in Step 10 above was reacted in the same manner as in Step 9 of Example 1 to give the title compound as colorless As a solid.

Melting point: 150-155 ° C

Ή-NMR (CDC / TS) 5 (ppm):

 1.16 (s, 3H), 1.24 (s, 3H), 1.26 (m, 3H), 1.27 (s, 9H), 1.52 (m, 1H),

1.79 (s, 3H), 1.92 (s, 1H), 2.08 (d, 1H, J = 16.1Hz), 2.19 (m, 2H),

 2.38-2.42 (m, 4H), 2.50 (m, 4H), 2.65 (m, 2H),

 3.35 (dd, 1H, J = 5.0Hz, 13.1Hz), 3.65 (m, 4H), 3.76 (m, 1H),

 4.04 (d, 1H, J = 8.8Hz), 4.23 (d, 1H, J = 7.8Hz), 4.31 (d, 1H, J = 8.8Hz),

 4.61 (br, 1H), 4.69 (d, 1H, J = 3.9Hz), 5.26 (br, 1H), 5.34 (d, 1H, J = 9.3Hz),

5.62 (d, 1H, J = 7.8Hz), 6.23 (br, 1H), 7.31-7.41 (m, 5H),

 7.51 (t, 2H, J = 7.5Hz), 7.60 (t, 1H, J = 7.5Hz), 8.16 (d, 2H, J = 7.5Hz).

MS-FAB: 887 (MH ⁺ )

Example 3 5

1 3 3

Replacement form (Rule 26)

Step 1: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-6,7-didehydro-1-0-dimethylsilyl-4-0- (ethyncarbonyl) -13-〇-triethylsilylpad Kachin III

 The compound obtained in Step 2 of Example 2 was reacted in the same manner as in Step 3 of Example 2 using ethyl chloroformate instead of cyclopropanecarbonyl chloride to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) 5 (ppm):

 -0.26 (d, 3H, J = 3 Hz), 0.09 (d, 3H, J = 3 Hz), 0.68 (m, 6H),

 1.02 (t, 9H, J = 7 Hz), 1.08 (s, 3H), 1.13 (s, 3H),

 1.39 (t, 3H, J = 7 Hz), 1.80 (s, 3H), 1.84 (s, 3H), 2.20 (m, 1H),

 2.30 (d, 1H, J = 9 Hz), 2.99 (m, 1H), 3.61 (t, 1H, J = 7 Hz),

 4.14 (m, 2H), 4.36 (m, 2H), 4.59 (m, 1H), 4.99 (m, 2H), 5.09 (m, 2H),

5.72 (d, 1H, J = 10 Hz), 5.83 (m, 1H), 5.85 (d, 1H, J = 7 Hz),

 6.00 (dd, 1H, J = 6, 10 Hz), 7.48 (t, 2H, J 2 8 Hz),

 7.58 (t, 1H, J = 8 Hz), 8.15 (d, 2H, J = 8 Hz).

MS-FAB: 753 (H ⁺ ).

Step 2: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-6,7-didehydro-4-0- (ethoxyquincarbonyl) baccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

1 H-NMR (CDCh / TS) (5 (ppm):

 1.08 (s, 3H), 1.10 (s, 3H), 1.39 (t, 3H, J = 7 Hz), 1.82 (s, 3H),

 1.85 (d, 3H, J = 1.5 Hz), 2.05 (s, 3H), 2.23-2.32 (m, 2H),

 2.36 (dd, 1H, J = 7, 16 Hz), 2.99 (m, 1H), 3.68 (m, 1H), 4.22 (m, 1H), 4

.29 (m, 2H), 4.33 (m, 1H), 4.52 (d, 1H, J = 8 Hz), 4.82 (br, 1H),

 5.02 (d, 1H, J = 10 Hz), 5.10 (dd, 1H, J = 1.5, 17 Hz),

 5.19 (d, 1H, J = 6 Hz), 5.77 (d, 1H, J = 10 Hz),

 5.82 (d, 1H, J = 7 Hz), 5.83 (m, 1H), 6.01 (dd, 1H, J = 6, 10 Hz),

7.48 (t, 2H, J = 8 Hz), 7.61 (t, 1H, J = 8 Hz), 8.14 (m, 2H).

1 3 4 MS-FAB: 580 (MH ⁺ ).

Step 3: 10-aryl-13-0-[(2R, 3S) -3 (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetox Ci-4-deacetyl-7-dexoxy-6,7-didehydro-4-0- (ethokincarbonyl) paccatin II I

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC1 ,, / TMS) 5 (ppm):

 -0.33 (s, 3H), -0.12 (s, 3H), 0.74 (s, 9H), 1.12 (s, 3H),

 1.26 (s, 3H), 1.33 (m, 3H), 1.35 (s, 9H), 1.72 (s, 3H), 1.88 (s, 3H),

2.18 (m, 1H), 2.28 (m, 1H), 2.58 (dd, 1H, J = 7, 15 Hz),

2.99 (m, 1H), 3.65 (t, 1H, J = 7 Hz), 4.21 (d, 1H, J = 7 Hz),

 4.32 (m, 1H), 4.38 (d, 1H, J = 9 Hz), 4.45-4.53 (m, 3H),

 5.02 (d, 1H, J = 10 Hz), 5.03 (dd, 1H, J = 1.5, 17 Hz),

 5.19 (d, 1H, J = 5 Hz), 5.36 (d, 1H, J = 10 Hz),

 5.46 (d, 1H, J = 10 Hz), 5.80 (d, 1H, J = 10 Hz), 5.86 (m, 1H),

 5.89 (d, 1H, J = 7 Hz), 6.02 (dd, 1H, J = 6, 10 Hz),

 6.19 (t, 1H, J = 8 Hz), 7.29-7.38 (m, 5H), 7.48 (t, 2H, J = 8 Hz),

7.61 (t, 1H, J = 8 Hz), 8.18 (d, 2H, J 2 8 Hz).

MS-FAB: 958 (H ⁺ ).

Step 4: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-4- Decetyl -7-deoxy-6,7-didehydro-4- 0- (ethoxycarbonyl) -10- (2-morpholinoethyl)

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

'Η -Image R (CDCh / TS) (5 (ppm):

 -0.33 (s, 3H), -0.12 (s, 3H), 0.74 (s, 9H), 1.12 (s, 3H),

 1.24 (s, 3H), 1.33 (m, 3H), 1.35 (s, 9H), 1.79 (s, 3H), 1.88 (s, 4H),

1 3 5 2.10-2.64 (m, 11H), 3.69 (m, 4H), 3.80 (dd, 1H, J = 5, 7 Hz),

4.21 (d, 1H, J = 7 Hz), 4.32 (m, 1H), 4.38 (d, 1H, J = 8 Hz),

4.49-4.54 (m, 3H), 5.20 (d, 1H, J = 6 Hz), 5.37 (br, 1H),

 5.47 (d, 1H, J = 10 Hz), 5.77 (d, 1H, J = 10 Hz),

 5.89 (d, 1H, J 2 7 Hz), 6.33 (dd, 1H, J = 6, 10 Hz),

 6.16 (t, 1H, J = 8 Hz), 7.29-7.38 (m, 5H), 7.48 (t, 2H, J = 8 Hz), 7.61 (t, 1H, J = 8 Hz), 8.18 (d, 2H , J = 8 Hz).

MS-FAB: 1031 (MH ⁺ ).

Step 5: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- phenylpropionyl] -10-deacetoxy-4-deacetyl-7-deoxy-6 , 7-Didehydro-40- (ethoxycarbonyl) -10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless amorphous solid.

Melting point: 115-120 ° C.

Ή-NMR (CDCl ₃ / TMS) 5 (ppm):

 1.10 (s, 3H), 1.20 (s, 3H), 1.26 (t, 3H, J = 7 Hz), 1.37 (s, 9H), 1.68 (s, 3H), 1.80 (s, 1H), 1.83 (s , 3H), 2.25-2.60 (m, 11H),

3.68 (m, 4H), 3.79 (m, 1H), 4.10 (m, 1H), 4.19 (m, 1H),

4.31 (d, 1H, J = 8 Hz), 4.38 (m, 1H), 4.60 (m, 2H), 5.21 (m, 1H), 5.28 (br, 1H), 5.48 (d, 1H, J = 10 Hz ), 5.74 (d, 1H, J = 10 Hz),

 6.08 (t, 1H, J = 8 Hz), 7.29-7.46 (m, 5H), 7.48 (t, 2H, J = 8 Hz), 7.61 (t, 1H, J = 8 Hz), 8.11 (d, 2H , J = 8 Hz).

MS-FAB: 917 (MH ⁺ ).

1 3 6 Example 3 6

137 Replacement paper (Rule 26) Step 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-methyl-3-phenyl-2- (triethylsilyl) oxypropionyl] -10- Deacetoxy-4-Decetyl-7-Deoquin-6,7-Didehydro-4-0- (Ethoxycarbonyl) Paccatin III

 The compound obtained in Step 2 of Example 35 was reacted in the same manner as in Step 1 of Example 4 to obtain the title compound as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TS} ) 5 (ppm):

 0.47-0.69 (m, 6H), 0.85 (t, 9H, J = 7 Hz), 1.12 (s, 3H), 1.24 (s, 3H),

1.28 (s, 9H), 1.39 (t, 3H, J = 7 Hz), 1.41 (s, 3H), 1.71 (s, 3H),

1.89 (s, 3H), 2.13-2.29 (m, 2H), 2.54-2.60 (m, 1H), 2.96-3.03 (m, 1H),

3.66 (t, 1H, J = 7 Hz), 4.24 (d, 1H, J = 7 Hz),

 4.43 (d, 1H, J = 8 Hz), 4.50 (d, 1H, J = 8 Hz), 4.57-4.67 (m, 2H),

5.03-5.19 (a 3H), 5.55 (d, 1H, J: 10 Hz), 5.78 (d, 1H, J = 10 Hz),

5.81-5.91 (m, 1H), 6.02 (dd, 1H, J = 6, 10 Hz),

 6.26 (t, 1H, J = 8 Hz), 7.28-7.47 (m, 7H), 7.57 (t, 1H, J = 8 Hz),

8.15 (d, 2H, J = 8 Hz).

Step 2: 10-aryl-13-O-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4 -Deasechi

13

Replacement paper (Kaikai IJ26) -7-Doxy-6,7-didehydro-4-0- (ethoxyquincarbonyl) noxtin 111 The compound obtained in the above Step 1 is reacted in the same manner as in Step 9 of Example 1 to give the title compound. Obtained as a colorless amorphous solid.

 Ή-N R (CDCh / TMS) (5 (ppm):

 1.13 (s, 3H), 1.24 (s, 3H), 1.33 (s, 9H), 1.39 (t, 3H, J27 Hz), 1.41 (s, 3H), 1.59 (s, 3H), 1.86 (s , 3H), 2.22-2.32 (m, 2H),

2.54-2.60 (m, 1H), 2.95-3.02 (m, 1H), 3.61-3.64 (m, 2H),

4.12 (d, 1H, J = 7 Hz), 4.35 (d, 1H, J = 8 Hz), 4.45-4.50 (m, 2H),

4.47 (d, 1H, J = 8 Hz), 5.02-5.13 (m, 3H), 5.69 (d, 1H, J = 10 Hz),

5.75-5.85 (m, 2H), 5.87 (d, 1H, J = 7 Hz),

 6.02 (dd, 1H, J = 6, 10 Hz), 6.17 (t, 1H, J = 8 Hz),

 7.28-7.48 (m, 7H), 7.60 (t, 1H, J = 8 Hz), 8.10 (d, 2H, J = 8 Hz).

Step 3: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4-decetyl- 7-Doxy-6,7-didehydro-4--4-〇- (Ethkincarbonyl) -10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Melting point: 125-130 ° C.

_{Ή-NMR (CDC1:, /} TS) 5 (ppm):

 1.10 (s, 3H), 1.20 (s, 3H), 1.30 (s, 9H), 1.36 (t, 3H, J = 7.5 Hz),

1.62 (s, 3H), 1.80 (s, 3H), 2.20-2.60 (m, 10H), 3.65 (s, 4H),

 3.79 (m, 1H), 4.10 (m, 1H), 4.32 (d, 1H, J = 8.5 Hz), 4.48 (m, 2H),

4.62 (d, 1H, J = 8.5 Hz), 5.09 (d, 1H, J = 10 Hz),

 5.28 (d, 1H, J = 5 Hz), 5.70 (d, 1H, J = 10 Hz),

 5.76 (d, 1H, J: 10 Hz), 5.85 (d, 1H, J = 7 Hz),

 6.01 (dd, 1H, J = 5, 10 Hz), 6.13 (br, 1H), 7.29-7.42 (m, 5H),

 7.46 (t, 2H, J = 7.5 Hz), 7.59 (t, 1H, J = 7.5 Hz),

 8.09 (d, 2H, J = 7.5 Hz)

1 3 8

Step 1: 10-aryl-13-0-[(2R.3S) -3- (tert-butynecarbonylamino) -2-methyl-3-phenyl-2- (trimethylsilyl) oxypropionyl] -10 -Desetoxy-7-Deoxy-7-Fluoropachatin III

 The compound obtained in Step 4 of Example 5 was reacted in the same manner as in Step 1 of Example 4 to obtain the title compound as a colorless amorphous solid.

Ή-NM (CDC / TMS) 5 (ppm):

 0.09 (s, 9H), 1.11 (s, 3H), 1.18 (s, 9H), 1.28 (s, 3H), 1.37 (s, 3H), 1.62 (s, 3H), 1.71 (s, 3H), 2.32 (s, 3H), 2.08-3.03 (m, 6H),

4.06 (t, 1H, J = 7 Hz), 4.20 (d, 1H, J = 7 Hz), 4.38 (s, 2H),

4.56 (dd, 1H, J = 3, 47Hz), 4.99-5.12 (m, 4H),

 5.50 (d, 1H, J 10 Hz), 5.74-5.81 (m, 2H), 6.35 (t, 1H, J = 8 Hz), 7.29-7.41 (m, 5H), 7.50 (t, 2H, J = 8 Hz), 7.58 (t, 1H, J = 8 Hz), 8.18 (d, 2H, J = 8 Hz).

Step 2: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroquinine-2-methyl-3-phenylpropionyl] -10-deacetoxy-7 -Deoxy -la- Fluoropaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

1 3 9/1

Replacement form (Rule 26) 1.12 (s, 3H), 1.22 (s, 9H), 1.26 (s, 3H), 1.34 (s, 3H), 1.66 (s, 3H),

1.70 (s, 3H), 2.62 (s, 3H), 2.15-3.06 (m, 6H), 3.61 (br, 1H),

 4.08 (dd, 1H, J = 5.5, 8 Hz), 4.21 (d, 1H, J = 7 Hz),

 4.37 (AB type d, 2H, J = 8.5 Hz), 4.55 (dd, 1H, J = 3, 47 Hz),

 5.05-5.11 (m, 4H), 5.52 (d, 1H, J = 10 Hz), 5.71-5.81 (m, 2H),

 6.31 (t, 1H, J = 8 Hz), 7.32-7.36 (m, 5H), 7.50 (t, 2H, J = 8 Hz),

7.59 (t, 1H, J = 8 Hz), 8.17 (d, 2H, J 8 Hz).

Step 3: 13-0-[(2R.3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-7-deoxy-7 α-Fluoro-10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless amorphous solid.

Melting point: 147-151 ° C.

'膽 -bundle (CDCh / TMS) δ (ppm):

 1.10 (s, 3H), 1.22 (s, 9H), 1.25 (s, 3H), 1.36 (s, 3H), 1.70 (s, 3H),

1.75 (s, 3H), 2.65 (s, 3H), 2.14-2.60 (m, 12H), 3.66-3.69 (m, 4H),

4.22-4.23 (m, 2H), 4.37 (AB type d, 2H, J = 8 Hz),

 4.53 (dd, 1H, J = 3, 47 Hz), 5.03-5.07 (m, 2H),

 5.53 (d, 1H, J-2 10 Hz), 5.75 (d, 1H, J-2 7 Hz),

 6.30 (t, 1H, J = 8 Hz), 7.32-7.37 (m, 5H), 7.50 (t, 2H, J = 8 Hz),

7.60 (t, 1H, J = 8 Hz), 8.17 (d, 2H, J = 8 Hz)

MS-FAB: 921 (MH ⁺ ).

1 4 0

BocHN o

141/1 Replacement paper (Kaikai IJ26) Step 1: 10-aryl-10-deacetoxy-4-decetyl-4-0-ethoxycarbonyl-13-0-triethylsilylpaccatin III

 10-aryl-7,13-bis (triethylsilyl) -10-deacetoxy-4-deacetyl-1-10-dimethylsilyl-4-〇-ethoxycarbonylbaccatin III was reacted in the same manner as in step 2 of Example 5 to give the title. The compound was obtained as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TMS} ) 5 (ppm):

 0.63-0.68 (m, 6H), 1.00 (t, 9H, J = 7 Hz), 1.10 (s, 3H), 1.15 (s, 3H),

1.40 (t, 3H, J = 7 Hz), 1.63 (s, 3H), 1.82-1.87 (m, 1H), 1.89 (s, 3H),

2.04-2.09 (m, 1H), 2.24-2.30 (m, 2H), 2.51-2.57 (m, 1H),

 2.91-2.96 (m, 1H), 3.87 (t, 1H, J = 8 Hz), 4.07 (d, 1H, J = 7 Hz),

4.20 (d, 1H, J = 8 Hz), 4.30-4.45 (m, 3H), 4.92-5.12 (m, 4H),

 5.65 (d, 1H, J = 7 Hz), 5.80-5.86 (m, 1H), 7.47 (t, 2H, J = 8 Hz),

7.59 (t, 1H, J = 8 Hz), 8.10 (d, 2H, J = 8 Hz).

Step 2: 10-aryl-10-deacetoxy-4-deacetyl-7-deokin-4-0-ethoxycarbonyl-7-fluoro-13-0-triethylsilylpaccatin III

1 4 1/2

Replacement form (Rule 26) The compound obtained in the above Step 1 was reacted in the same manner as in Step 3 of Example 5 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 0.62-0.68 (m, 6H), 1.00 (t, 9H, J = 7 Hz), 1.07 (s, 3H), 1.15 (s, 3H),

1.39 (t, 3H, J = 7 Hz), 1.67 (s, 3H), 1.84 (s, 3H), 2.07-3.05 (m, 6H),

2.49-2.70 (m, 3H), 4.07-4.21 (m, 4H), 4.32-4.44 (m, 2H),

 4.55 (dd, 1H, J = 3, 47 Hz), 4.92 (t, 1H, J = 8 Hz),

 4.98-5.09 (m, 3H), 5.70 (d, 1H, J 7 Hz), 5.72-5.81 (m, 1H),

 7.48 (t, 2H, J = 8 Hz), 7.60 (t, 1H, J = 8 Hz),

 8.14 (d, 2H, J = 8 Hz).

Step 3: 10-aryl-10-deacetoxy-4-deacetyl-7-deoxy-4-〇-ethoxycarbonyl-7α-fluoropaccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.08 (s, 6H), 1.39 (t, 3H, J = 7 Hz), 1.65 (s, 3H), 1.89 (s, 3H),

2.12-3.06 (m, 6H), 4.10-4.44 (m, 6H),

 4.55 (ddd, 1H, J = 2, 4.5, 9 Hz), 4.80 (br, 1H),

 5.00 (dd, 1H, J = 1.5, 9 Hz), 5.07-5.13 (m, 2H), 5.75-5.93 (m, 1H),

7.51 (t, 2H, J = 8 Hz), 7.60 (t, 1H, J = 8 Hz),

 8.13 (d, 2H, J = 8 Hz).

Step 4: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-4 -Deacetyl-7-dexoxy-4-0-ethoxyquincarbonyl-7α-fluorobaccatin III The compound obtained in the above Step 3 was reacted in the same manner as in Step 1 of Example 4, and then reacted with the step of Example 1. The reaction was carried out in the same manner as in 9 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCl ₃ / TMS) {5 (ppm):

 1.11 (s, 3H), 1.20 (s, 3H), 1.34 (s, 9H), 1.37-1.39 (m, 6H),

1.63 (s, 3H), 1.68 (s, 3H), 2.20-3.07 (m, 6H),

1 4 2 3.70 (s, 1H), 4.06 (dd, 1H, J = 4, 8 Hz), 4.12 (d, 1H, J = 7 Hz), 4.33-4.62 (m, 5H), 5.02 (d, 1H, J = 10 Hz), 5.07-5.13 (m, 2H),

5.20 (d, 1H, J = 10 Hz), 5.66-5.82 (m, 3H), 6.11 (t, 1H, J = 8 Hz), 7.28-7.48 (m, 7H), 7.59 (t, 1H, J = 8 Hz), 8.09 (d, 2H, J = 8 Hz).

Step 5: 13-◦-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoquin-4-deacetyl -7-Doxy-4- 0-Ethoxycarbonyl-7-Fluoro-10- (2-morpholinoethyl)

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 10 of Example 1 to give the title compound as a colorless solid.

Melting point: 130-132 ° C.

Ή-NMR (CDCh / TMS) δ (ppm):

 1.09 (s, 3H), 1.19 (s, 3H), 1.33 (s, 9H), 1.36-1.41 (m, 6H),

 1.67 (s, 3H), 1.73 (s, 3H), 2.16-2.64 (m, 12H), 3.63-3.68 (m, 4H), 4.13 (d, 1H, J = 7 Hz), 4.19 (t, 1H, J = 5.5 Hz), 4.33-4.58 (m, 5H), 5.08 (d, 1H, J = 10 Hz), 5.20 (d, 1H, J-7 Hz), 5.75-5.77 (m, 2H),

6.10 (t, 1H, J = 8 Hz), 7.29-7.48 (m, 7H), 7.59 (t, 1H, J = 8 Hz), 8.09 (d, 2H, J two 8 Hz).

MS-FAB: 951 (MH ⁺ ).

Example 3 9

1 4 3

Replacement form (Rule 26)

143/1 Replacement paper (Kaikai IJ26) Step 1: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10-deacetoxy-2- Debenzyl-7-deoxy-7 / 3, 8 / 3-methylene-10- (2-morpholinoethyl) -19-norpaccatin III

 1 4 3/2

Replacement form (Rule 26) Example 18 89 mg of the compound obtained in Step 6 of Step 8 was dissolved in 4.5 ml of dry dichloromethane, and Tron B (89 ml, 40% w / w methanol solution) was added at -78 ° C, followed by heating at the same temperature. For 5 minutes and at -10 ° C for 7 minutes. After diluting the reaction solution with ethyl acetate, 1N hydrochloric acid (10 ml) was added to stop the reaction, extraction was performed with ethyl acetate, and the mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine in this order. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the obtained residue was purified by silica gel thin-layer chromatography (developing solvent, chloroform: methanol = 95: 5 (v / v)). 41 m of the title compound were obtained as a colorless amorphous solid.

Ή-NMR (CDC / TS) 5 (ppm):

 -0.34 (s, 3H), -0.12 (s, 3H), 0.76 (s, 9H), 1.10 (s, 3H),

 1.24 (s, 3H), 1.44 (s, 9H), 1.61 (m, 1H), 1.77 (s, 3H), 1.90 (br, 1H),

2.08-2.22 (m, 2H), 2.38-2.58 (m, 14H), 3.69 (m, 5H),

 3.81 (d, 1H, J = 8 Hz), 3.98 (br, 1H), 4.42 (s, 1H),

 4.52 (d, 1H, J = 9.5 Hz), 4.65 (d, 1H, J = 9.5 Hz),

 4.79 (d, 1H, J = 4 Hz), 5.22 (d, 1H, J = 10 Hz),

 5.50 (d, 1H, J = 10 Hz), 6.21 (m, 1H), 7.3 (t, 1H, J = 8 Hz),

 7.28 (m, 1H), 7.36 (m, 2H)

MS-FAB: 897 (MH ⁺ ).

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3- phenylpropionyl] -10-deacetoxy-2-debenzoyl-7-deoxy-2 -0- (3-Methoxybenzoyl)-7 β, 8β-Methylene-10- (2-morpholinoethyl)-19-Norpaccatin III

 13 m of the compound obtained in the above step 1 was dissolved in 0.4 ml of dry tetrahydrofuran. Then, at -78 ° C, lithium bis (trimethylsilyl) amide (1 M tetrahydrofuran solution, 73 ml) and 10 ml of 3-methoxybenzoyl chloride were added, and the mixture was stirred at the same temperature for 120 minutes. The reaction solution was diluted with ethyl acetate, and the reaction was stopped by adding a saturated aqueous solution of ammonium chloride.The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off. Purification was performed using a force gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (v / v)). Obtained

1 4 4 The obtained compound was reacted in the same manner as in Step 9 of Example 1 to obtain 4 mg of the title compound as a white solid.

Melting point: 110-115. C.

 Ή-NMR (CDCh / TS) 5 (ppm):

 1.20 (s, 3H), 1.22 (s, 3H), 1.28 (s, 9H), 1.56 (m, 1H), 1.80 (s, 3H),

2.12 (d, 1H, J = 16 Hz), 2.20 (m, 2H), 2.37-2.49 (m, 12H),

 2.56 (m, 1H), 3.72 (s, 4H), 3.75 (m, 1H), 3.90 (s, 3H),

 4.03 (d, 1H, J = 8.5 Hz), 4.28 (d, 1H, J = 7.5 Hz),

 4.38 (d, 1H, J = 8.5 Hz), 4.59 (s, 1H), 4.75 (d, 1H, J = 3.5 Hz),

5.28 (br, 1H), 5.33 (d, 1H, J = 9 Hz), 5.65 (d, 1H, J = 7 Hz),

 6.2 (m, 1H), 7.13 (dd, 1H, J = 2.5, 8 Hz), 7.30-7.43 (m, 6H),

 7.69 (br, 1H), 7.76 (d, 1H, J = 8 Hz).

MS-FAB: 917 (MH ⁺ ).

Example 40

1 4 5

Replacement paper (Kaikai IJ26)

Step 1: 10-aryl-13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propioni -]-10-Deacetoxy-7-Deoquin-7 ^, 83-Methylene-19-norpaccatin III

 Example 18 Compound obtained in Step 4 of 8 and (3R, 4R) -1- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyl) oxy-4- (2-furyl) -2- The azetidinone was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) (5 (ppm):

 -0.16 (s, 3H), 0.02 (s, 3H), 0.79 (s, 9H), 1.21 (s, 3H), 1.22 (s, 3H),

1.28 (s, 9H), 1.55 (m, 1H), 1.73 (s, 3H), 1.83 (br, 1H),

 2.10-2.25 (m, 4H), 2.42-2.48 (m, 2H), 2.45 (s, 3H), 2.99 (m, 1H),

1 4 5/2

Replacement form (Rule 26) 3.69 (t, 1H, J 7 Hz), 4.05 (d, 1H, J = 9 Hz), 4.29 (m, 2H),

4.70 (d, 1H, J 2 Hz), 4.76 (d, 1H, J = 3.5 Hz),

 5.03 (d, 1H, J 10 Hz), 5.10 (dd, 1H, J = 1.5, 17 Hz),

5.24 (d, 1H, J 10 Hz), 5.38 (d, 1H, J = 10 Hz),

5.65 (d, 1H, J 8 Hz), 5.83 (m, 1H), 6.21 (m, 1H),

6.26 (t, 1H, J 6 Hz), 6.35 (m, 1H), 7.37 (s, 1H),

7.49 (t, 2H, J 7.5 Hz), 7.57 (t, 1H, J = 7.5 Hz),

8.14 (d, 2H, J 7.5 Hz)

MS-FAB: 918 (H ⁺ ).

Step 2: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetoxy-7-deokin-7yS , 8 / 3-Methylene-10- (2-morpholinoethyl) -19-norpaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 and then reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 130-135 ° C.

Ή-NMR (CDC / TMS) (5 (ppm):

 1.20 (s, 6H), 1.30 (s, 9H), 1.57 (m, 1H), 1.82 (s, 3H), 1.87 (br, 1H), 2.10 (d, 1H, J = 16 Hz), 2.22 (m , 2H), 2.30-2.60 (m, bandits),

2.38 (s, 3H), 3.70 (m, 4H), 4.71 (m, 1H), 4.76 (m, 1H),

4.05 (d, 1H, J = 8.5 Hz), 4.29 (m, 2H), 4.69 (s, 1H),

 4.75 (d, 1H, J 2 3 Hz), 5.22 (d, 1H, J = 10 Hz),

 5.35 (d, 1H, J = 10 Hz), 5.68 (d, 1H, J = 8 Hz),

 6.22 (t, 1H, J = 9 Hz), 6.32 (m, 1H), 6.39 (m, 1H), 7.42 (s, 1H), 7.49 (t, 2H, J = 7.5 Hz), 7.59 (t, 1H , J = 7.5 Hz),

8.16 (d, 2H, J = 7.5Hz).

MS-FAB: 877 (MH ⁺ ).

1 4 6 Example 4 1

147 Replacement sheet (Rule 26)

147/1 Replacement paper (Rule 26) Step 1: 10-aryl-10-deacetoxy-2-debenzoyl-7-deoxy-7 / 3,8 / S-methylene-19-norpaccatin Ι Π

 Example 19 100 mg of the compound obtained in Step 1 of 9 was dissolved in 1.5 ml of dry tetrahydrofuran, and sodium bis (2-methoxyethoxyquin) aluminum 180 ^ 1 was added thereto at 0 ° C for 20 minutes. Stirred. Ethyl acetate, a saturated aqueous solution of potassium tartrate, and water were added to the reaction mixture, and the mixture was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified using silica gel thin-layer chromatography (developing solvent; hexane: ethyl acetate = 3: 2 (v / v)) to obtain 70 mg of the title compound as a colorless amorphous solid. Was.

Ή-NMR (CDCh / TMS) (5 (ppm):

 0.68 (m, 6H), 0.99 (m, 9H), 1.10 (s, 3H), 1.19 (s, 3H),

 1.56 (dd, 1H, J = 5, 7 Hz), 1.65 (br, 1H), 1.76 (s, 3H),

 1.92 (dd, 1H, J = 8, 15 Hz), 2.05-2.20 (m, 7H),

 2.34 (d, 1H, J = 7 Hz), 2.45 (m, 1H), 2.94 (m, 1H),

 3.61 (dd, 1H, J = 6, 8 Hz), 3.77 (d, 1H, J = 7 Hz),

 3.94 (t, 1H, J = 7 Hz), 4.51 (d, 1H, J = 9 Hz),

 .60 (d, 1H, J = 9 Hz), 4.77 (d, 1H, J = 4 Hz),

 4.93 (t, 1H, J = 8 Hz), 4.96 (m, 1H), 5.05 (dd, 1H, J = 1.5, 17 Hz), .81 (m, 1H).

1 4 Ί / 2

Replacement form (Rule 26) MS-FAB: 560 (MH ⁺ ).

Process 2: 10-aryl-2--2-〇- (3-chlorobenzoyl) -10-deacetoxy-2-devenzyl-7-deoxy-7 / 3,8 yS-methylene-19-norpaccatin III

 Dissolve 35 mg of the compound obtained in the above step 1 in 1.05 ml of dry toluene, and add 196 mg of 3-chlorobenzoic acid, 258 mg of dicyclohexylcarbodiimide and 153 mg of 4-dimethylaminopyridine at room temperature. The mixture was stirred at 60 ° C for 1 day. The reaction solution was diluted with ethyl acetate, and the reaction was stopped by adding a saturated aqueous solution of tartaric acid under ice-cooling. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; hexane: ethyl acetate = 4: 1 (v / v)). Next, the obtained compound was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) d (ppm):

 1.10 (s, 3H), 1.18 (s, 3H), 1.52 (t, 1H, J = 6 Hz), 1.78 (s, 1H), 1.89 (s, 3H), 2.12 (d, 1H, J = 16 Hz ), 2.20-2.32 (m, 4H),

2.28 (s, 3H), 2.46 (dt, 1H, J = 4.5, 16 Hz), 3.00 (m, 1H),

3.71 (dd, 1H, J = 6, 8 Hz), 4.02 (d, 1H, J = 9 Hz),

4.27 (d, 1H, J = 8 Hz), 4.36 (d, 1H, J = 8 Hz),

 4.77 (d, 1H, J = 4 Hz), 4.82 (t, 1H, J '-7 Hz),

 5.01 (d, 1H, J = 10 Hz), 5.09 (dd, 1H, J = 1.5, 17 Hz),

 5.56 (d, 1H, J = 8 Hz), 5.82 (m, 1H), 7.43 (d, 1H, J = 8 Hz),

7.57 (m, 1H), 8.00 (d, 1H, J-8 Hz), 8.16 (m, 1H).

MS-FAB: 585 (MH ⁺ ).

Step 3: 10 aryl-13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl ]-2-0- (3-Chlorobenzoyl) -10-Deacetoxy-2- Debenzoyl-7-Doxy-7 / 3,8 / 3-Methylene-19-Norpaccatin III

 The compound obtained in the above Step 2 and (3R, 4R) -l- (tert-butoxycarbonyl) -3- (tert-butyldimethylsilyl) oxy-4- (2-furyl) -2-azetidinone were prepared according to Example 1. The reaction was carried out in the same manner as in Step 8, to obtain the title compound as a colorless amorphous solid.

1 4 8 Ή-NMR (CDCh / TMS) (5 (ppm):

 -0.16 (s, 3H), 0.02 (s, 3H), 0.79 (s, 9H), 1.21 (s, 3H), 1.22 (s, 3H),

1.28 (s, 9H), 1.55 (m, 1H), 1.73 (s, 3H), 1.77 (br, 1H),

 2.10-2.25 (m, 4H), 2.38-2.49 (m, 2H), 2.45 (s, 3H), 3.00 (m, 1H),

3.69 (m, 1H), 4.03 (d, 1H, J = 8 Hz), 4.29 (m, 2H), 4.70 (m, 1H),

 4.76 (d, 1H, J = 4 Hz), 5.03 (d, 1H, J = 10 Hz),

 5.10 (dd, 1H, J = 1.5, 17 Hz), 5.24 (d, 1H, J = 10 Hz),

 5.35 (d, 1H, J = 10 Hz), 5.61 (d, 1H, J = 8 Hz), 5.83 (m, 1H),

 6.21 (m, 1H), 6.23 (m, 1H), 6.35 (m, 1H), 7.37 (m, 1H),

 7.45 (t, 1H, J = 8 Hz), 7.54 (d, 1H, J = 8 Hz),

 8.03 (d, 1H, J = 8 Hz), 8.15 (m, 1H).

MS-FAB: 952 (H ⁺ ).

Step 4: 13-0-[(2R, 3R) -3- (tert-butoxycarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -2-0- (3-chloro Benzyl) -10-deacetoxy-2-debenzoyl-7-deoxy-7 3,8 / S-methylene-10- (2-morpholinoethyl) -19-norpaccatin Π Ι

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 9 of Example 1 and then reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 125-130 ° C.

_{'Η - NMR (CDC1 3 /} TMS) δ (ppm):

 1.20 (s, 3H), 1.30 (s, 9H), 1.57 (m, 1H), 1.82 (s, 4H),

2.12 (d, 1H, J = 16 Hz), 2.22 (m, 2H), 2.30-2.60 (m, 7H),

2.38 (s, 3H), 3.70 (m, 4H), 3.77 (t, 1H, J = 6 Hz),

 4.02 (d, 1H, J = 8.5 Hz), 4.29 (m, 2H), 4.68 (d, 1H, J = 2.5 Hz), 4.78 (d, 1H, J = 3.5 Hz), 5.22 (d, 1H, J = 10 Hz), 5.32 (br, 1H),

5.61 (d, 1H, J = 8 Hz), 6.20 (t, 1H, J = 8.5 Hz),

 6.30 (d, 1H, J = 3.5 Hz), 6.37 (m, 1H), 7.42 (s, 1H),

 .45 (t, 1H, J = 8 Hz), 7.57 (m, 1H), 8.04 (d, 1H, J = 8 Hz),

 . 17 (s, 1H).

1 4 9 MS -FAB: 911 (MH-).

Example 4 2

 150

Replacement form (Rule 26) Step 1: 10-aryl-10-deacetoxy-2-debenzoyl-7-deoxy-2-0- (3-methoxybenzoyl) -7 β, 8β-methylene-19-norpaccatin III

 Example 41 The compound obtained in Step 1 of Example 41 was reacted in the same manner as in Step 2 of Example 41 by using 3-methoxybenzoic acid instead of 3-chlorobenzoic acid, and then the process of Example 1 was repeated. The reaction was carried out in the same manner as in 7 to give the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 1.10 (s, 3H), 1.16 (s, 3H), 1.52 (dd, 1H, J = 5, 7 Hz), 1.82 (br, 1H), 1.89 (s, 3H), 2.10 (d, 1H, J = 16 Hz), 2.20-2.25 (m, 3H),

2.25 (s, 3H), 2.35 (dd, 1H, J = 7, 16 Hz),

2.44 (dt, 1H, J = 4.5, 16 Hz), 3.00 (m, 1H),

 3.71 (dd, 1H, J 2 6 '8 Hz), 3.87 (s, 3H), 4.04 (d, 1H, J = 8 Hz),

4.33 (d, 1H, J = 8 Hz), 4.36 (d, 1H, J two 8 Hz),

 4.75 (d, 1H, J = 4.5 Hz), 4.83 (d, 1H, J = 8 Hz), 5.01 (m, 1H),

 5.08 (dd, 1H, J = 1.5, 17 Hz), 5.60 (d, 1H, J = 7 Hz), 5.82 (m, 1H),

7.15 (m, 1H), 7.39 (m, 1H), 7.67 (m, 1H), 7.73 (d, 1H, J = 8 Hz).

1 5 0/1

Replacement forms (Rule 26) MS-FAB: 580 (MID.

Step 2: 10-aryl-13-〇-[(2R, 3R) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3- (2-furyl) propionyl] -10- deacetoxy-2-debenzoyl -7-deokin-2- 0- (3-methoxybenzoyl) -7 β β-methylene-19-norpaccatin III

 The compound obtained in the above step 1 and (3R, 4R) -1- (tert-butynecarbonyl) -3- (tert-butyldimethylsilyl) oxy-4- (2-furyl) -2-azetidinone were prepared in Examples The reaction was carried out in the same manner as in Step 8 of 1 to give the title compound as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TMS} ) (5 (ppm):

 -0.16 (s, 3H), 0.02 (s, 3H), 0.79 (s, 9H), 1.21 (s, 3H), 1.22 (s, 3H),

1.28 (s, 9H), 1.55 (m, 1H), 1.73 (s, 3H), 1.84 (br, 1H),

 2.10-2.25 (m, 4H), 2.43 (s, 3H), 2.40-2.48 (m, 2H), 2.99 (m, 1H),

3.69 (m, 1H), 3.84 (s, 3H), 4.05 (d, 1H, J = 8 Hz),

 4.29 (d, 1H, J = 8 Hz), 4.35 (d, 1H, J = 8 Hz), 4.69 (m, 1H),

4.75 (d, 1H, J = 4 Hz), 5.03 (d, 1H, J = 10 Hz),

 5.12 (dd, 1H, J 2 1.5, 17 Hz), 5.24 (d, 1H, J = 10 Hz),

 5.31 (d, 1H, J = 10 Hz), 5.65 (d, 1H, J = 8 Hz), 5.83 (m, 1H),

 6.21 (m, 1H), 6.23 (m, 1H), 6.33 (m, 1H), 7.12 (m, 1H), 7.37 (s, 1H),

7.39 (t, 2H, J = 8 Hz), 7.67 (m, 1H), 7.77 (d, 2H, J = 8 Hz).

MS-FAB: 948 (MH ⁺ ).

Step 3: 13-0-[(2R, 3R) -3- (tert-butynecarbonylamino) -3- (2-furyl) -2-hydroxypropionyl] -10-deacetoxy-2-debenzoyl- 7-Doxy-2-0- (3 methoxybenzoyl) -7β, 8β-methylene-10- (2-morpholinoethyl) -19-norpaccatin ΠΙ

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 9 of Example 1 and then reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 120-125 ° C.

Ή-NMR (CDCh / TMS) (5 (ppm):

 1.20 (s, 3H), 1.28 (s, 9H), 1.55 (m, 1H), 1.80 (s, 3H), 1.88 (s, 3H),

1 5 1 2.12 (d, 1H, J = 16 Hz), 2.20 (m, 2H), 2.30-2.60 (m, 7H), 2.38 (s, 3H),

3.70 (m, 4H), 3.77 (d, 1H, J = 8 Hz), 4.89 (s, 3H),

 4.04 (d, 1H, J = 8 Hz), 4.28 (d, 1H, J = 8 Hz),

 4.35 (d, 1H, J = 8 Hz), 4.68 (s, 1H), 4.76 (d, 1H, J = 4 Hz),

 5.20 (d, 1H, J = 10 Hz), 5.32 (br, 1H), 6.21 (t, 1H, J = 8 Hz),

6.30 (d, 1H, J = 3 Hz), 6.37 (m, 1H), 7.14 (dd, 1H, J = 3, 8 Hz), 7.41 (t, 1H, J = 8 Hz), 7.42 (s, 1H), 7.68 (br, 1H),

 7.76 (d, 1H, J = 8 Hz).

MS-FAB: 907 (MH +).

Example 4 3

1 5 2

Replacement form (Rule 26)

152/1 Replacement paper (Kaikai IJ26) Step 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butynecarbonylamino) -2- (tert-butyldimethylnyl) oxy-3-phenylpropionyl] -2 -0- (3-cyclobenzoyl) -10-deacetoxy-2-debenzoyl-7-deokin-7 ^, 83-methylen-19-norpaccatin III

 Example 4 The compound obtained in Step 2 of 1 was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 -0.32 (s, 3H),-0.12 (s, 3H), 0.73 (s, 9H), 1.21 (s, 3H),

 1.25 (s, 3H), 1.26 (s, 9H), 1.55 (m, 1H), 1.73 (s, 3H), 1.80 (br, 1H),

2.18-2.25 (m, 4H), 2.38-2.49 (m, 2H), 2.51 (s, 3H), 2.99 (m, 1H),

3.69 (t, 1H, J = 8 Hz), 4.03 (d, 1H, J = 8 Hz),

 4.28 (d, 1H, J = 7 Hz), 4.30 (d, 1H, J = 8 Hz), 4.49 (s, 1H),

 4.79 (m, 1H), 5.02 (d, 1H, J = 10 Hz), 5.12 (d, 1H, J = 17 Hz),

1 5 2/2

Replacement paper (Kaikai Ij26) 5.30 (br, 1H), 5.41 (br, 1H), 5.61 (d, 1H, J = 7 Hz), 5.82 (m, 1H), -6.25 (t, 1H, J = 9 Hz), 7.25-7.36 ( m, 5H), 7.44 (t, 2H, J = 8 Hz),

7.56 (d, 1H, J = 8 Hz), 8.03 (d, 1H, J = 8 Hz), 8.17 (s, 1H).

MS-FAB: 962 (MH ⁺ ).

Step 2: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroquinine-3-phenylpropionyl] -2-0- (3-chlorobenzoyl) -10 -Deacetoxy-2_ debenzoyl-7-deoxy-7 / 3,8 / 3-methylene-10- (2-morpholinoethyl) -19-norbaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 and then reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Ή-NMR (CDCh / TMS) (5 (ppm):

 1.20 (s, 3H), 1.21 (s, 3H), 1.28 (s, 9H), 1.55 (m, 1H), 1.80 (s, 4H), 2.08-2.23 (m, 3H), 2.30-2,60 ( m, 10H), 2.37 (s, 3H), 3.70 (m, 4H), 3.76 (t, 1H, J = 6 Hz), 4.02 (d, 1H, J = 9 Hz), 4.29 (m, 2H),

 4.57 (s, 1H), 4.76 (d, 1H, J = 3.5 Hz), 5.28 (br, 1H),

 5.31 (d, 1H, J = 10 Hz), 5.60 (d, 1H, J = 7 Hz), 6.20 (br, 1H),

7.29-7.40 (m, 5H), 7.46 (t, 2H, J = 8 Hz), 7.58 (d, 1H, J = 8 Hz), 8.03 (d, 1H, J = 8 Hz), 8.18 (s, 1H ).

MS-FAB: 921 (MH10).

1 5 3

Step 1: 10-deacetoxy-2-debenzoyl-7- 0-methyl-10- (2-morpholinoethyl) -13- 0-triethylsilylpaccatin III

 The compound obtained in Step 3 of Example 10 was reacted in the same manner as in Step 1 of Example 41 to give the title compound as a colorless amorphous solid.

Ή-NR (CDC / TS) 5 (ppm):

 0.65 (m, 6H), 1.00 (t, 9H, J = 8 Hz), 1.02 (s, 3H), 1.12 (s, 3H),

1.60 (s, 3H), 1.76 (m, 1H), 1.91 (s, 3H), 2.02 (m, 1H), 2, 18 (s, 3H),

2.22-2.75 (m, 10H), 3.24 (s, 3H), 3.59 (d, 1H, J = 7 Hz),

 3.70 (m, 4H), 3.82 (d, 1H, J2 7 Hz), 3.95 (m, 1H),

 4.68 (d, 1H, J 2 7 Hz), 4.62 (d, 1H, J = 7 Hz),

 4.92 (t, 1H, J = 8 Hz), 5.02 (d, 1H, J = 7 Hz).

 MS-FAB: 665 (H +).

Step 2: 10-Deacetoxy-2-debenzoyl-2-0- (3-methoxybenzoyl) _7-0-methyl-10- (2-morpholinoethyl) -13-0-Triethylsilylpaccatin III In Step 1 above The obtained compound was reacted with 3-methoxybenzoic acid in place of 3-chlorobenzoic acid in the same manner as in Step 2 of Example 41 to give the title compound as a colorless amorphous solid

1 5 4/1

Replacement form (Rule 26) As obtained.

 Ή-NMR (CDC / TMS) (5 (ppm):

 0.67 (m, 6H), 1.01 (t, 9H, J = 7 Hz), 1.10 (s, 6H), 1.66 (s, 3H), 1.70-2.80 (m, 12H), 1.88 (s, 3H), 2.28 (s, 3H), 3.25 (s, 3H),

3.64 (m, 1H), 3.69 (m, 4H), 3.85 (s, 3H), 3.94 (m, 1H), 4.00 (m, 1H), 4.18 (d, 1H, J = 8.5 Hz), 4.8 (dd, 1H, J = 6.5, 10.5 Hz),

 4.33 (d, 1H, J = 8.5 Hz), 4.91 (t, 1H, J = 8 Hz),

 5.03 (d, 1H, J = 8 Hz), 5.59 (d, 1H, J = 7 Hz), 7.14 (m, 1H),

7.37 (t, 1H, J = 8 Hz), 7.63 (s, 1H), 7.69 (d, 1H, J = 8 Hz).

MS-FAB: 800 (MH ⁺ ).

Step 3: 10-Deacetoxy-2-debenzoyl-2-0- (3-methoxybenzoyl) -7-0-methyl-10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-N R (CDCh / TMS) (5 (ppm):

 1.06 (s, 3H), 1.12 (s, 3H), 1.66 (s, 3H), 1.75 (m, 1H), 2.05 (s, 3H), 2.26 (s, 3H), 2.30-2.75 (m, 11H) , 3.26 (s, 3H), 3.64 (m, 1H),

3.69 (m, 4H), 3.85 (s, 3H), 3.99 (m, 1H), 4.09 (d, 1H, J = 7 Hz), 4.16 (d, 1H, J = 8.5 Hz), 4.32 (d, 1H , J = 8.5 Hz), 4.81 (br, 1H),

5.00 (d, 1H, J 2 7 Hz), 5.59 (d, 1H, J = 7 Hz),

 7.12 (dd, 1H, J = 3, 8.5 Hz), 7.36 (t, 1H, J = 8 Hz),

7.64 (d, 1H, J-2 Hz), 7.70 (d, 1H, J = 8 Hz).

Step 4: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2--2-methyl-3-phenylpropionyl] -10-deacetoxy-2-debenzoyl-2 -0-(3-Methoxybenzoyl) -7-0-methyl-10- (2-morpholinoethyl) baccatin III

 The compound obtained in Step 3 of Reference Example 4 and Step 3 of Reference Example 4 was reacted in the same manner as in Step 1 of Example 4, and then reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

1 5 5 Melting point: 125- 130 ° C.

 Ή-NMR (CDCh / TS) (5 (ppm):

 1.14 (s, 3H), 1.22 (s, 9H), 1.24 (s, 3H), 1.25 (s, 3H), 1.68 (s, 3H),

1.79 (s, 3H), 1.79 (m, 1H), 2.17-2.75 (m, 11H), 2.62 (s, 3H),

 3.27 (s, 3H), 3.59 (br, 1H), 3.65 (m, 1H), 3.67 (br, 4H), 3.89 (s, 3H),

3.97 (m, 2H), 4.19 (d, 1H, J = 8.5 Hz), 4.38 (d, 1H, J = 8.5 Hz),

5.01 (m, 2H), 5.54 (d, 1H, J = 10 Hz), 5.64 (d, 1H, J = 7 Hz),

 6.9 (t, 1H, J = 8 Hz), 7.13 (dd, 1H, J22, 8 Hz), 7.36 (m, 5H),

7.38 (m, 1H), 7.66 (m, 1H), 7.74 (d, 1H, J = 8 Hz).

MS-FAB: 963 (MH ⁺ ).

Example 45

1 56

Replacement paper (Kaikai IJ26)

156/1 Replacement paper (Kaikai IJ26) Process II: 10-Deacetoxy-2-debenzoyl-2-0- (3,5-difluorobenzoyl) -7-0-methyl-10- (2-morpholinoethyl) -13-0-triethylsilyl Baccatin III

 The compound obtained in Step 1 of Example 44 was reacted with 3,5-difluorobenzoic acid in place of 3-chlorobenzoic acid in the same manner as in Step 2 of Example 41 to give the title compound as an amorphous amorphous substance Obtained as a crystalline solid.

1 56/2

Replacement form (Rule 26) Ή-NMR (CDC / TMS) (5 (ppm):

 0.67 (m, 6H), 1.01 (t, 9H, J = 7 Hz), 1.08 (s, 3H), 1.10 (s, 3H), 1.66 (s, 3H), 1.75 (m, 1H), 1.99 (s , 3H), 2.10-2.75 (m, 11H),

2.29 (s, 3H), 3.26 (s, 3H), 3.64 (m, 1H), 3.69 (m, 4H), 3.95 (m, 1H), 4.01 (d, 1H, J = 7 Hz), 4.14 (d , 1H, J = 8.5 Hz),

 4.28 (d, 1H, J = 8.5 Hz), 4.90 (t, 1H, J = 8 Hz),

 5.03 (d, 1H, J = 8 Hz), 5.52 (d, 1H, J = 7 Hz), 7.06 (m, 1H),

7.60 (d, 2H, J = 5.5 Hz).

MS-FAB: 806 (H ⁺ ).

Step 2: 10-Deacetoxy-2-debenzoyl-2-0- (3,5-difluorobenzoyl) -7-0-methyl-10- (2_morpholinoethyl) paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.06 (s, 3H), 1.10 (s, 3H), 1.68 (s, 3H), 2.08 (s, 3H),

1.70-2.72 (m, 12H), 2.30 (s, 3H), 3.28 (s, 3H), 3.69 (s, 5H),

 4.00 (m, 1H), 4.10 (m, 1H), 4.13 (d, 1H, J = 8.5 Hz),

 4.29 (d, 1H, J = 8.5 Hz), 4.82 (br, 1H), 5.00 (d, 1H, J = 8 Hz),

 5.52 (d, 1H, J = 7 Hz), 7.02 (m, 1H), 7.60 (d, 1H, J = 5.5 Hz).

Step 3: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-2-debenzoyl-2 -0- (3,5-difluorobenzoyl) -7-0-methyl-10- (2-morpholinoethyl) paccatin III

 The compound obtained in Step 2 of Reference Example 4 and Step 3 of Reference Example 4 was reacted in the same manner as in Step 1 of Example 4, and then reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 130-135 ° C.

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.12 (s, 3H), 1.22 (s, 9H), 1.23 (s, 311), 1.38 (s, 3H), 1.69 (s, 3H),

1 5 7 1.78 (s, 3H), 1.78 (m, 1H), 2.10-2.72 (m, 11H), 2.61 (s, 3H),

3.25 (s, 3H), 3.68 (br, 4H), 3.95 (m, 3H), 4.15 (d, 1H, J = 8.5 Hz),

4.31 (d, 1H, J = 8.5 Hz), 5.00 (m, 2H), 5.50 (d, 1H, J: 10 Hz),

 5.59 (d, 1H, J = 7 Hz), 6.26 (m, 1H), 7.03 (m, 1H), 7.18-7.33 (m, 5H), 7

.66 (m, 2H).

MS-FAB: 969 (MH ⁺ ).

Example 4 6

1 5 8

Replacement paper (Kaikai IJ26)

Step 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-methyl-3- (4-tolyl) -2- (trimethylsilyl) oxypropionyl ]-10- Deacetoquin-7- 0- Methylbaccatin ΙΠ

The compound obtained in Step 10 of Example 11 and the compound obtained in Step 3 of Reference Example 5 were reacted in the same manner as in Step 1 of Example 4 to obtain the title compound as a colorless amorphous solid. _{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 0.11 (s, 9H), 1.14 (s, 3H), 1.16 (s, 9H), 1.28 (s, 3H), 1.38 (s, 3H), 1.69 (s, 3H), 1.79 (s, 3H), 1.76 -1.82 (m, 1H), 2.03-2.09 (m, 1H), 2.22-2.34 (m, 2H), 2.35 (s, 3H), 2.67-2.72 (m, 1H), 2.69 (s, 3H), 2.96 -3.04 (m, 1H), 3.24 (s, 3H), 3.76 (t, 1H, J = 7 Hz),

1 5 8/2

Replacement form (Rule 26) 3.92-3.98 (m, 2H), 4.21 (d, 1H, J = 8 Hz), 4.31 (d, 1H, J = 8 Hz),

4.94-5.08 (m, 3H), 5.45 (d, 1H, J = 10 Hz), 5.65 (d, 1H, J = 7 Hz),

5.80-5.90 (m, 1H), 6.36 (t, 1H, J = 8 Hz), 7.15 (s, 4H),

7.47 (t, 2H, J = 8 Hz), 7.56 (t, 1H, J = 8 Hz),

 8.14 (d, 2H, J = 8 Hz).

Step 2: 10-aryl-13-0 _ [(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-tolyl) propionyl] -10 -Deacetoxy-7-0-Methylbaccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TS) δ (ppm):

 1.15 (s, 3H), 1.23 (s, 9H), 1.25 (s, 3H), 1.37 (s, 3H), 1.68 (s, 3H), 1.70 (s, 3H), 1.75-1.82 (m, 1H) , 2.15-2.31 (m, 3H), 2.36 (s, 3H),

2.61 (s, 3H), 2.65-2.73 (m, 1H), 2.93-3.00 (m, 1H), 3.25 (s, 3H),

 3.56 (br, 1H), 3.77 (t, 1H, J = 7 Hz), 3.93 (dd, 1H, J = 7, 10 Hz), 3.98 (d, 1H, J = 7 Hz), 4.21 (d, 1H , J = 8 Hz),

 4.31 (d, 1H, J 8 Hz), 4.99-5.11 (m, 3H), 5.50 (d, 1H, J = 10 Hz),

5.65 (d, 1H, J 7 Hz), 5.75-5.86 (m, 1H), 6.29 (t, 1H, J = 8 Hz),

7.17 (d, 2H, J 8 Hz), 7.25 (d, 2H, J = 8 Hz),

 7.48 (t, 2H, J 8 Hz), 7.58 (t, 1H, J 2 8 Hz),

 8.13 (d, 2H, J 8 Hz).

Step 3: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3- (4-tolyl) propionyl] -10-deacetoxy- 7- 0-methyl -10- (2-morpholinoethyl)

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 158-162 ° C.

■ H-NMRCCDCh / TMS) δ (ppm):

 1.14 (s, 3H), 1.22 (s, 9H), 1.24 (s, 3H), 1.37 (s, 3H), 1.69 (s, 3H),

1 5 9 1.84 (s, 3H), 1.75-1.82 (m, 1H), 2.14-2.75 (m, 11H), 2.36 (s, 3H),

2.64 (s, 3H), 3.26 (s, 3H), 3.60 (br, 1H), 3.67 (s, 4H),

 3.95-4.02 (m, 3H), 4.21 (d, 1H, J = 8 Hz), 4.32 (d, 1H, J = 8 Hz),

5.00-5.02 (m, 2H), 5.48 (d, 1H, J: 10 Hz), 5.65 (d, 1H, J = 7 Hz),

6.31 (t, 1H, J = 8 Hz), 7.18 (d, 2H, J = 8 Hz),

 7.25 (d, 2H, J = 8 Hz), 7.48 (t, 2H, J = 8 Hz),

 7.58 (t, 1H, J = 8 Hz), 8.13 (d, 2H, J = 8 Hz).

MS-FAB: 947 (MH ⁺ ).

Example 4 7

1 6 0

Replacement paper (Kaikai IJ26)

160/1 Replacement Form (Rule 26) 13- 0- [(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10- [2- (cyclopropylamino) ethyl ] I 10-Deacetoxy-7-0-Methylbaccatin III

 The compound obtained in Step 12 of Example 11 was reacted with cyclopropylamine instead of morpholine in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 140-143 ° C.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 0.32-0.33 (m, 2H), 0.43-0.44 (m, 2H), 1.14 (s, 3H), 1.23 (s, 9H),

1.39 (s, 3H), 1.58-2.75 (m, 7H), 1.69 (s, 3H), 1.76 (s, 3H),

 2.62 (s, 3H), 3.27 (s, 3H), 3.85 (t, 1H, J = 6 Hz),

 3.94 (dd, 1H, J = 10, 7 Hz), 3.99 (d, 1H, J = 7.5 Hz),

 4.20 (d, 1H, J = 9 Hz), 4.31 (d, 1H, J = 9 Hz), 4.99-5.05 (m, 2H),

5.55 (d, 1H, J = 10 Hz), 5.64 (d, 1H, J = 7 Hz),

1 6 0/2

Replacement paper (26) 6.29 (t, 1H, J = 8 Hz), 7.33-7.37 (m, 5H), 7.48 (t, 2H, J = 8 Hz),

7.58 (t, 1H, J two 8 Hz), 8.13 (d, 2H, J = 8 Hz).

MS-FAB: 903 (MH ⁺ ).

Example 4 8

1 6 1

Replacement form (Rule 26) J26 I

0 H

7, 13-0-Bis (triethylsilyl) notchtin III was reacted in the same manner as in Step 2 of Example 5 to obtain the title compound as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 0.61-0.73 (m, 6H), 1.02 (t, 9H, J = 8 Hz), 1.11 (s, 3H), 1.18 (s, 3H),

1.80 (s, 3H), 1.83-1.90 (m, 1H), 2.00 (s, 3H), 2.12-2.26 (m, 2H),

 2.24 (s, 3H), 2.29 (s, 3H), 2.51 (d, 1H, J = 4 Hz), 2.52-2.59 (m, 1H),

3.80 (d, 1H, J = 7 Hz), 4.15 (d, 1H, J = 8 Hz),

 4.30 (d, 1H, J = 8 Hz), 4.44-4.49 (m, 1H), 4.94-5.00 (m, 2H),

 5.62 (d, 1H, J = 7 Hz), 6.31 (s, 1H), 7.48 (t, 2H, J 2 8 Hz),

 7.61 (t, 1H, J = 8 Hz), 8.09 (d, 2H, J = 8 Hz).

Step 2: 7-0-methylthiomethyl -13-0_ triethylsilylpaccatin III The compound obtained in the above step 1 was reacted in the same manner as in step 5 of Example 9 to obtain the title compound as a colorless amorphous solid. Was.

 Ή-NR (CDCh / TMS) 5 (ppm):

 0.63-0.75 (m, 6H), 1.02 (t, 9H, J = 8 Hz), 1.13 (s, 3H), 1.19 (s, 3H),

1.74 (s, 3H), 1.81-1.89 (m, 1H), 2.12 (s, 3H), 2.15 (s, 3H),

 2.19 (s, 3H), 2.17-2.28 (m, 2H), 2.30 (s, 3H), 2.80-2.87 (m, 1H),

 3.89 (d, 1H, J = 7 Hz), 4.15 (d, 1H, J = 8 Hz), 4.30-4.38 (m, 2H),

4.67 (s, 2H), 4.93 (t, 1H, J = 9 Hz), 4.98 (d, 1H, J = 9.5 Hz),

 5.64 (d, 1H, J = 7 Hz), 6.56 (s, 1H), 7.48 (t, 2H, J = 8H2),

 7.61 (t, 1H, J = 8 Hz), 8.09 (d, 2H, J = 8 Hz).

Process 3: 7-0-Fluoromethyl -13-〇- Triethylunrilpaccatin III

 100 mg of the compound obtained in the above step 2 was dissolved in 2 ml of dichloromethane and cooled with ice. Then, 45 m of N-odosuccinimide and 0.035 ml of getylamino sulfur trifluoride were added, and the mixture was stirred for 1 hour. To the reaction solution was added a saturated aqueous solution of sodium bicarbonate, and the mixture was vigorously stirred for about 5 minutes. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was developed and purified by silica gel thin-layer chromatography (developing solvent: ethyl acetate: hexane = 4: 1 (v / v)) to give 61.5 mg of the title compound as colorless crystals.

1 6 2 _{'HN R (CDC1 3 / TMS} ) δ (pm):

 0.63-0.73 (m, 6H), 1.02 (t, 9H, J = 8 Hz), 1.15 (s, 6H), 1.75 (s, 3H),

1.99-2.03 (m, 1H), 2.04 (s, 3H), 2.14-2.27 (m, 2H), 2.21 (s, 3H),

2.30 (s, 3H), 2.70-2.78 (m, 1H), 3.87 (d, 1H, J = 7 Hz),

 4.14 (d, 1H, J = 8 Hz), 4.27-4.32 (m, 2H), 4.92-4.97 (m, 2H),

 5.27 (dd, 1H, J = 3.5, 43 Hz), 5.36 (dd, 1H, J-3.5, 38.5 Hz),

 5.62 (d, 1H, J = 7 Hz), 6.35 (s, 1H), 7.48 (t, 2H, J = 8 Hz),

 7.61 (t, 1H, J = 8 Hz), 8.08 (d, 2H, J = 8 Hz).

Process 4: 7-0-Fluoromethylbaccatin ΠΙ

 The compound obtained in the above Step 3 was reacted in the same manner as in Step 7 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.08 (s, 3H), 1.15 (s, 3H), 1.76 (s, 3H), 1.99-2.05 (m, 1H),

2.10 (s, 3H), 2.21 (s, 3H), 2.27-2.30 (m, 2H), 2.29 (s, 3H),

2.71-2.79 (m, 1H), 3.92 (d, 1H, J = 7 Hz), 4.14 (d, 1H, J = 8 Hz), 4.28-4.32 (m, 2H), 4.86 (br, 1H), 4.97 (d, 1H, J = 9 Hz),

 5.23 (dd, 1H, J = 3, 44 Hz), 5.37 (dd, 1H, J = 3, 40 Hz),

5.63 (d, 1H, J = 7 Hz), 6.36 (s, 1H), 7.48 (t, 2H, J = 8 Hz),

7.61 (t, 1H, J = 8 Hz), 8.10 (d, 2H, J = 8 Hz).

Process 5: 10-Decetyl -7-0-Fluoromethylbaccatin III

 3.10 g of the compound obtained in the above step 4 was dissolved in a mixed solvent of 60 ml of ethanol and 20 ml of tetrahydrofuran, and 19 ml of hydrazine monohydrate was added under ice-cooling, followed by stirring at room temperature for 90 minutes. The reaction solution was poured into ice water, extracted with ethyl acetate, washed with a 1N aqueous hydrochloric acid solution (twice), a saturated aqueous sodium bicarbonate solution, and a saturated saline solution in that order, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (eluent, solvent: chloroform: methanol = 100: 1 (v / v)) to give the title compound 2.80 as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 1.09 (s, 3H), 1.10 (s, 3H), 1.81 (s, 3H), 1.84-1.98 (m, 1H),

1 6 3 2.09 (d, 3H, J = 1.5 Hz), 2.26-2.29 (m, 2H), 2.30 (s, 3H),

 2.63-2.70 (m, 1H), 4.00 (d, 1H, J = 7 Hz), 4.18 (d, 1H, J = 8 Hz), 4.33 (d, 1H, J = 8 Hz), 4.35 (dd, 1H) , J = 7, 10 Hz),

 4.88 (d, 1H, J = 8 Hz), 4.98 (d, 1H, J = 8 Hz),

 5.12 (dd, 1H, J = 3, 22 Hz), 5.26 (dd, 1H, J = 3, 27 Hz),

5.31 (s, 1H), 5.62 (d, 1H, J = 7 Hz), 7.48 (t, 2H, J = 8 Hz),

7.61 (t, 1H, J = 8 Hz), 8.10 (d, 2H, J = 8 Hz).

Step 6: 10-Decetyl-7-0-fluoromethyl-10-0- (methylthio) thiocarbonylbaccatin III

 The compound obtained in the above Step 5 was reacted in the same manner as in Step 1 of Example 6 to obtain the title compound as a pale yellow amorphous solid.

Ή-NMR (CDC / TMS) 5 (ppm):

 1.10 (s, 3H), 1.24 (s, 3H), 1.78 (s, 3H), 2.00-2.32 (m, 3H),

2.19 (s, 3H), 2.30 (s, 3H), 2.64 (s, 3H), 2.74-2.82 (m, 1H),

 3.92 (d, 1H, J = 7 Hz), 4.15 (d, 1H, J = 8 Hz), 4.29-4.34 (m, 2H), 4.88 (t, 1H, J = 8 Hz), 4.97 (d, 1H , J = 8 Hz),

 5.20 (dd, 1H, J = 3, 24 Hz), 5.35 (dd, 1H, J = 3, 20 Hz),

 5.67 (d, 1H, J = 7 Hz), 7.42 (s, 1H), 7.49 (t, 2H, J = 8 Hz),

7.62 (t, 1H, J = 8 Hz), 8.11 (d, 2H, J = 8 Hz).

Step 7: 10-Deacetoxy -7-0 Fluoromethyl-10- (2-formylethyl) Noccatin II I

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 2 of Example 6 to obtain the title compound as colorless amorphous crystals.

Ή-NR (CDC / TMS) (5 (ppm):

 1.06 (s, 3H), 1.11 (s, 3H), 1.70 (s, 3H), 1.78-1.93 (m, 2H),

 1.98 (d, 3H, J = 1 Hz), 2.24-2.27 (m, 2H), 2.29 (s, 3H),

 2.44-2.70 (m, 4H), 3.91 (dd, 1H, J = 5, 7 Hz), 4.07 (d, 1H, J = 7 Hz),

4.18 (d, 1H, J = 8 Hz), 4.32 (d, 1H, J = 8 Hz),

 4.48 (dd, 1H, J-7, 10 Hz), 4.84 (t, 1H, J = 8 Hz),

1 6 4 4.99 (d, 1H, J = 8 Hz), 5.14 (dd, 1H, J = 3, 24 Hz),

5.28 (dd, 1H, J = 3, 22 Hz), 5.60 (d, 1H, J = 7 Hz),

7.48 (t, 2H, J = 8 Hz), 7.61 (t, 1H, J = 8 Hz),

8.10 (d, 2H, J = 8 Hz), 9.78 (s, 1H).

Step 8: 10-Deacetoxy-7_0-Fluoromethyl-10- (3-hydroxypropionyl)

 The compound obtained in the above Step 7 was reacted in the same manner as in Step 3 of Example 6 to obtain the title compound as colorless amorphous crystals.

Ή-NMR (CDCh / TMS) (5 (ppm):

 1.05 (s, 3H), 1.11 (s, 3H), 1.51-1.61 (m, 4H), 1.70 (s, 3H),

 1.87-1.93 (m, 1H), 1.98 (s, 3H), 2.20-2.27 (m, 2H), 2.30 (s, 3H),

2.63-2.70 (m, 2H), 3.62-3.72 (m, 2H), 3.93 (t, 1H, J = 6 Hz),

 4.10 (d, 1H, J = 7 Hz), 4.18 (d, 1H, J = 8 Hz),

 4.32 (d, 1H, J = 8 Hz), 4.50 (dd, 1H, J = 7, 10 Hz),

 4,84 (t, 1H, J = 8 Hz), 5.00 (d, 1H, J = 8 Hz),

 5.14 (dd, 1H, J = 3, 22 Hz), 5.28 (dd, 1H, J = 3, 29 Hz),

 5.61 (d, 1H, J = 7 Hz), 7.48 (t, 2H, J = 8 Hz),

 7.60 (t, 1H, J = 8 Hz), 8.10 (d, 2H, J = 8 Hz).

Step 9: 10-aryl-10-deacetoxy-7-0-fluoromethylbaccatin III The compound obtained in the above step 8 is reacted in the same manner as in the step 4 of the example 6, and then the step 5 of the example 6 is carried out. The same reaction was performed to obtain the title compound as a pale yellow amorphous solid. Ή-NMR (CDCh / TMS) (5 (ppm):

 1.07 (s, 3H), 1.12 (s, 3H), 1.71 (s, 3H), 1.89-1.93 (m, 1H),

 1.95 (d, 3H, J 2 1 Hz), 2.20-2.27 (m, 2H), 2.29 (s, 3H),

 2.31-2.45 (m, 1H), 2.61-2.68 (m, 1H), 2.85-2.92 (m, 1H),

 4.00 (dd, 1H, J = 6, 8 Hz), 4.10 (d, 1H, J = 7 Hz),

 4.18 (d, 1H, J = 8 Hz), 4.31 (d, 1H, J = 8 Hz),

 4.45 (dd, 1H, J = 7, 10 Hz), 4.85 (t, 1H, J = 8 Hz),

 4.98-5.11 (m, 3H), 5.12 (dd, 1H, J = 3, 20 Hz),

1 6 5 5.26 (dd, 1H, J = 3, 28 Hz), 5.61 (d, 1H, J = 7 Hz),

 5.73-5.83 (m, 1H), 7.47 (t, 2H, J = 8 Hz), 7.60 (t, 1H, J = 8 Hz),

8.10 (d, 2H, J two 8 Hz).

Step 10: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2- (tert-butyldimethylsilyl) oxy-3-phenylpropionyl] -10- Deacetoxy-7- 0-Fluoromethylbaccatin III

 The compound obtained in the above Step 9 was reacted in the same manner as in Step 8 of Example 1 to obtain the title compound as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 -0.31 (s, 3H), -0.11 (s, 3H), 0.75 (s, 9H), 1.16 (s, 3H),

 1.24 (s, 3H), 1.31 (s, 9H), 1.73 (s, 3H), 1.79 (s, 3H),

 1.85-1.99 (m, 1H), 2.14-2.38 (m, 3H), 2.56 (s, 3H), 2.64 (m, 1H),

2.89- 2.95 (m, 1H), 3.96 (t, 1H, J = 6 Hz), 4.03 (d, 1H, J = 7 Hz), 4.22 (d, 1H, J = 8 Hz), 4.33 (d, 1H , J = 8 Hz),

 4.43 (dd, 1H, J = 7, 10 Hz), 4.51 (s, 1H), 4.98-5.29 (m, 6H),

 5.44 (d, 1H, J = 10 Hz), 5.77 (d, 1H, J = 7 Hz), 5.79—5.85 (m, 1H), 6.26 (t, 1H, J = 8 Hz), 7.25-7.39 On, 5H), 7.49 (t, 2H, J = 8 Hz), 7.59 (t, 1H, J = 8 Hz), 8.11 (d, 2H, J = 8 Hz).

Step 11: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-7-〇- Fluoromecchi Rubaccatin III

 The compound obtained in the above Step 10 was reacted in the same manner as in Step 9 of Example 1 to give the title compound as a colorless amorphous solid.

_{'HN R (CDC1 3 / TMS} ) δ (ppm):

 1.16 (s, 3H), 1.22 (s, 3H), 1.34 (s, 9H), 1.72 (s, 3H), 1.75 (s, 3H),

1.90- 1.97 (m, 1H), 2.20-2.28 (m, 2H), 2.37 (s, 3H), 2.33-2.41 (m, 1H), 2.59-2.67 (m, 1H), 2.86-2.92 (m, 1H ), 3.32 (d, 1H, J = 5 Hz),

 3.96-4.01 (m, 2H), 4.20 (d, 1H, J = 8 Hz), 4.31 (d, 1H, J = 8 Hz), 4.40 (dd, 1H, J = 7, 10 Hz), 4.61 (s , 1H), 4.94-5.13 (m, 4H),

1 6 6 5.21-5.8 (m, 2H), 5.39 (d, 1H, J = 10 Hz), 5.66 (d, 1H, J = 7 Hz), 5.70-5.80 (m, 1H), 6.19 (t, 1H, J = 8 Hz), 7.30-7.42 (m, 5H),

7.49 (t, 2H, J = 8 Hz), 7.60 (t, 1H, J = 8 Hz),

8.10 (d, 2H, J = 8 Hz).

Step 12: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-3-phenylpropionyl] -10-deacetoxy-7-0-fluoromethyl- 10- (2-morpholinoethyl)

 The compound obtained in the above Step 11 was reacted in the same manner as in Step 10 of Example 1 to give the title compound as a colorless solid.

Melting point: 142-146 ° C.

Ή-NMR (CDC / TMS) δ (ppm):

 1.15 (s, 3H), 1.20 (s, 3H), 1.34 (s, 9H), 1.72 (s, 3H), 1.85 (s, 3H),

2.38 (s, 3H), 1.60-2.70 (m, 12H), 3.68 (m, 4H), 4.00-4.06 (m, 2H),

4.19 (d, 1H, J = 8 Hz), 4.31 (d, 1H, J = 8 Hz),

 4.41 (dd, 1H, J2 7, 10 Hz), 4.60 (s, 1H), 4.96 (d, 1H, J = 8 Hz),

5.11 (dd, 1H, J-3, 27.5 Hz), 5.22-5.28 (m, 2H),

 5.41 (d, 1H, J: 10 Hz), 5.65 (d, 1H, J = 7 Hz),

 6.17 (t, 1H, J = 8 Hz), 7.30-7.42 (m, 5H), 7.49 (t, 2H, J = 8 Hz),

7.61 (t, 1H, J = 8 Hz), 8.10 (d, 2H, J = 8 Hz).

MS-FAB: 937 (MH ⁺ ).

Example 4 9

1 6 7

Replacement form (Rule 26)

Step 1: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-methyl-3-phenyl-2- (triethylsilyl) oxypropionyl] -10-deacetox 7- 0-Fluoromethylbaccatin III

 The compound obtained in Step 9 of Example 48 and Step 3 of Reference Example 4 was reacted in the same manner as in Step 1 of Example 4 to obtain the title compound as a colorless amorphous solid.

_{'H-NMR (CDC1 3 /} TMS) δ (ppm):

 0.50-0.74 (m, 6H), 0.86 (t, 9H, J = 7 Hz), 1.17 (s, 12H),

 1.30 (s, 3H), 1.38 (s, 3H), 1.74 (s, 3H), 1.78 (s, 3H),

 1.93-2.11 (m, 2H), 2.29-2.36 (m, 2H), 2.60-2.66 (m, 1H), 2.70 (s, 3H),

2.90-2.97 (m, 1H), 3.93 (t, 1H, J = 7 Hz), 4.01 (d, 1H, J = 7 Hz),

4.23 (d, 1H, J = 8 Hz), 4.33 (d, 1H, J = 8 Hz),

4.41 (dd, 1H, J = 7, 10 Hz), 4.97—5.13 (m, 4H),

 5.25 (dd, 1H, J = 2.5, 26 Hz), 5.49 (d, 1H, J = 10 Hz),

5.69 (d, 1H, J = 7 Hz), 5.77-5.85 (m, 1H), 6.37 (t, 1H, J = 8 Hz), 7.31-7.36 (m, 5H), 7.50 (t, 2H, J = 8 Hz), 7.57 (t, 1H, J = 8 Hz), 8.14 (d, 2H, J = 8 Hz).

Step 2: 10-aryl-13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-7- 0-Fluoromethylbaccatin ΠΙ

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 9 of Example 1 to obtain the title compound as a colorless amorphous solid.

'H-NMRCCDCh / TMS) δ (ppm):

 1.17 (s, 3H), 1.3 (s, 9H), 1.27 (s, 3H), 1.36 (s, 3H), 1.70 (s, 3H), 1.73 (s, 3H), 1.89-1.98 (m, 1H), 2.15-2.40 (m, 3H), 2.62 (s, 3H),

2.60-2.67 (m, 1H), 2.86-2.93 (m, 1H), 3.60 (s, 3H),

 3.97 (dd, 1H, J = 6, 8.5 Hz), 4.01 (d, 1H, J = 7 Hz),

4.21 (d, 1H, J = 8 Hz), 4.33 (d, 1H, J = 8 Hz),

 4.40 (dd, 1H, J = 7, 10 Hz), 4.97-5.13 (m, 4H),

 5.25 (dd, 1H, J = 3, 24 Hz), 5.54 (d, 1H, J = 10 Hz),

l 6 8 5.67 (d, 1H, J = 7 Hz), 5.71-5.80 (m, 1H), 6.31 (t, 1H, J = 8 Hz), 7.32-7.36 (m, 5H), 7.49 (t, 2H, J = 8 Hz), 7.59 (t, 1H, J = 8 Hz), 8.13 (d, 2H, J = 8 Hz).

Step 3: 13-0-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroxy-2-methyl-3-phenylpropionyl] -10-deacetoxy-7-0-fluoromethyl -10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 152-155. C.

Ή-NMR (CDCh / TMS) δ (ppm):

 1.16 (s, 3H), 1.23 (s, 9H), 1.25 (s, 3H), 1.39 (s, 3H), 1.73 (s, 3H),

1.79 (s, 3H), 2.64 (s, 3H), 1.90-2.70 (m, 12H), 3.68 (m, 4H),

 4.01-4.04 (m, 2H), 4.21 (d, 1H, J = 8 Hz), 4.33 (d, 1H, J = 8 Hz),

4.42 (dd, 1H, J = 7, 10 Hz), 4.98-5.13 (m, 4H),

 5.25 (dd, 1H, J = 3, 20 Hz), 5.54 (d, 1H, J = 10 Hz),

 5.67 (d, 1H, J = 7 Hz), 6.30 (t, 1H, J = 8 Hz), 7.32-7.40 (m, 5H),

7.49 (t, 2H, J = 8 Hz), 7.59 (t, 1H, J = 8 Hz),

 8.13 (d, 2H, J = 8 Hz).

MS-FAB: 951 (MH ⁺ ).

Example 50

1 6 9

o

Step 1: 10-aryl-10-deacetoxy-7- 0-fluoromethyl-13- 0-triethylsilylpaccatin III

 Example 48 The compound obtained in Step 9 of 8 was reacted in the same manner as in Step 3 of Example 1 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDCh / TMS) 5 (ppm):

 0.64-0.70 (m, 6H), 1.02 (t, 9H, J = 7 Hz), 1.12 (s, 3H), 1.13 (s, 3H),

1.70 (s, 3H), 1.90-1.96 (m, 1H), 1.90 (s, 3H), 2.10-2.37 (m, 4H),

2.29 (s, 3H), 2.59-2.67 (m, 1H), 2.86-2.91 (m, 1H),

 3.96 (dd, 1H, J 26, 8 Hz), 4.03 (d, 1H, J = 7 Hz),

 4.18 (d, 1H, J = 8 Hz), 4.31 (d, 1H, J = 8 Hz),

 4.44 (dd, 1H, J = 7, 10 Hz), 4.91 (t, 1H, J = 9 Hz),

 4.98-5.09 (m, 3H), 5.10 (dd, 1H, J = 3, 25 Hz),

 5.24 (dd, 1H, J = 3, 30 Hz), 5.61 (d, 1H, J = 7 Hz),

 5.72-5.83 (m, 1H), 7.47 (t, 2H, J = 8 Hz), 7.60 (t, 1H, J = 8 Hz),

8.09 (d, 2H, J = 8 Hz).

Step 2: 10-aryl-10-deacetoxy-1-0-dimethylsilyl-7-〇-fluoro

1 7 0/2

Replacement form (Rule 26) Methyl -13- 0- triethylsilyl paccatin III

 The compound obtained in the above Step 1 was reacted in the same manner as in Step 1 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDC / TMS) (5 (ppm):

 -0.25 (d, 3H, J = 2.5 Hz), 0.06 (d, 3H, J = 2.5 Hz), 0.66-0.73 (m, 6H), 1.03 (t, 9H, J = 7 Hz), 1.08 (s, 3H), 1.12 (s, 3H), 1.69 (s, 3H), 1.89 (s, 3H), 1.90-1.95 (m, 1H), 2.22-2.39 (m, 3H), 2.30 (s, 3H), 2.57 -2.65 (m, 1H), 2.87-2.93 (m, 1H), 3.93 (dd, 1H, J = 6, 8 Hz),

4.01 (d, 1H, J = 7 Hz), 4.25 (AB type d, each 1H, J = 9 Hz),

4.40 (dd, 1H, J = 7, 10 Hz), 4.53 (m, 1H), 4.92-4.99 (m, 3H),

 5.05-5.13 (m, 2H), 5.23 (dd, 1H, J = 3, 30 Hz),

 5.69 (d, 1H, J = 7 Hz), 5.75-5.85 (m, 1H), 7.47 (t, 2H, J = 8 Hz), 7.59 (t, 1H, J = 8 Hz), 8.09 (d, 2H , J = 8 Hz).

Step 3: 10-aryl-10-deacetoxy-4-deacetyl-1-〇-dimethylsilyl-7-7-0-fluoromethyl-13-13-0-triethylsilylpaccatin III

 The compound obtained in the above Step 2 was reacted in the same manner as in Step 2 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NR (CDCh / TMS) 5 (ppm):

 -0.28 (d, 3H, J = 3 Hz), 0.02 (d, 3H, J = 3 Hz), 0.74-0.85 (m, 6H),

0.97 (s, 3H), 1.08-1.13 (m, 12H), 1.59 (s, 3H), 1.90 (s, 3H),

 1.94-2.02 (m, 1H), 2.46-2.59 (m, 3H), 2.80 (dd, 1H, J = 2, 13 Hz),

2.84-2.89 (m, 1H), 3.76-3.80 (m, 1H), 4.00-4.06 (m, 1H),

 4.24 (d, 1H, J = 9 H), 4.32 (d, 1H, J = 9 Hz), 4.56-4.58 (m, 1H),

4.67-4.75 (m, 2H), 5.00-5.13 (m, 3H), 5.25 (dd, 1H, J = 3, 24 Hz),

5.57 (d, 1H, J = 7 Hz), 5.75-5.83 (m, 1H), 7.44 (t, 2H, J = 8 Hz), 7.56 (t, 1H, J = 8 Hz), 8.12 (d, 2H) , J = 8 Hz).

Step 4: 10-aryl-10-deacetoxy-4-deacetyl-1-0-dimethylsilyl-4--0-ethoxyquincarbonyl-7-0-fluoromethyl-13-0-triethylsilylbaccatin 1Π

1 7 1 The compound obtained in the above Step 3 was reacted in the same manner as in Step 3 of Example 9 to obtain the title compound as a colorless amorphous solid.

_{Ή-NMR (CDC1 3 / TMS} ) 5 (ppm):

 -0.30 (d, 3H, J = 3 Hz), 0.06 (d, 3H, J = 3 Hz), 0.64-0.70 (m, 6H),

1.02 (t, 9H, J = 7 Hz), 1.12 (s, 6 H), 1.41 (t, 3H, J = 7 Hz),

 1.69 (s, 3H), 1.90 (s, 3H), 1.92-1.97 (m, 1H), 2.22-2.34 (m, 2H),

2.57-2.64 (m, 1H), 2.87-2.94 (m, 1H), 3.91 (dd, 1H, J = 6, 8 Hz),

4.04 (d, 1H, J = 7 Hz), 4.13-4.21 (m, 1H),

 4.26 (AB evening d, each 1H, J = 9 Hz), 4.35-4.43 (m, 2H),

 4.53-4.56 (m, 1H), 4.94-5.14 (m, 4H), 5.25 (dd, 1H, J = 3, 30 Hz),

5.71 (d, 1H, J = 7 Hz), 5.74-5.84 (m, 1H), 7.46 (t, 2H, J = 8 Hz),

7.57 (t, 1H, J = 8 Hz), 8.10 (d, 2H, J = 8 Hz).

Step 5: 10-aryl-10-deacetoxy-4-deacetyl-4-0-ethoxycarbonyl-7-0-fluoromethylbaccatin III

 The compound obtained in the above Step 4 was reacted in the same manner as in Step 4 of Example 2 to obtain the title compound as a colorless amorphous solid.

Ή-NMR (CDCh / TMS) 5 (ppm):

 1.07 (s, 3H), 1.13 (s, 3H), 1.39 (t, 3H, J = 7 Hz), 1.70 (s, 3H),

1.90 to 1.94 (m, 1H), 1.97 (s, 3H), 2.22-2.43 (m, 2H), 2.62-2.69 (m, 1H),

2.86-2.93 (m, 1H), 4.02 (dd, 1H, J 26, 8 Hz), 4.13-4.25 (m, 3H),

4.31-4.39 (m, 3H), 4.84 (br, 1H), 4.98-5.15 (m, 4H),

 5.26 (dd, 1H, J = 3, 30 Hz), 5.63 (d, 1H, J = 7 Hz),

 5.74-5.83 (m, 1H), 7.48 (t, 2H, J = 8 Hz), 7.59 (t, 1H, J = 8 Hz),

8.11 (d, 2H, J = 8 Hz).

Step 6: 10-aryl-13-〇-[(2R, 3S) -3 (tert-butoxycarbonylamino) -2-methyl-3-phenyl-2- (triethylsilyl) oxypropionyl] -10-deacetox C-4-Decetyl-4-0-Ethynecarbonyl-7-0-Fluoromethylbaccatin III

 The compound obtained in Step 5 above and the compound obtained in Step 3 of Reference Example 4 were combined with the compound of Example 4

1 7 2 The reaction was carried out in the same manner as in Step 1 to obtain the title compound as a colorless amorphous solid.

 'H-NMRCCDCh / T S) δ (ppm):

 0.43-0.86 (m, 6H), 0.84 (t, 9H, J = 7 Hz), 1.17 (s, 3H), 1.24 (s, 3H), 1.27 (s, 9H), 1.39 (t, 3H, J = 7 Hz), 1.44 (s, 3H), 1.76 (s, 3H), 1.83 (s, 3H), 1.92-1.98 (m, 1H), 2.10-2.16 (m, 1H), 2.35-2.44 (m, 2H ), 2.61-2.69 (m, 1H), 2.91-2.95 (m, 1H), 3.99 (t, 1H, J = 7 Hz),

4.20 (d, 1H, J = 7 Hz), 4.30 (s, 2H), 4.40 (dd, 1H, J = 7, 10 Hz), 4.64-4.73 (m, 2H), 4.98-5.15 (m, 4H) , 5.24 (dd, 1H, J = 3, 30 Hz), 5.54 (d, 1H, J = 10 Hz), 5.69 (d, 1H, J = 7 Hz), 5.76-5.83 (m, 1H), 6.29 ( t, 1H, J = 8 Hz), 7.30-7.45 (m, 7H), 7.56 (t, 1H, J = 8 Hz), 8.12 (d, 2H, J = 8 Hz).

Step 7: 13-◦-[(2R, 3S) -3- (tert-butoxycarbonylamino) -2-hydroquinine-2-methyl-3-phenylpropionyl] -10-deacetoxy-4-decetyl- 4- 0-ethoxycarbonyl-7-〇-fluoromethyl-10- (2-morpholinoethyl) paccatin III

 The compound obtained in the above Step 6 was reacted in the same manner as in Step 9 of Example 1 and then reacted in the same manner as in Step 10 of Example 1 to obtain the title compound as a colorless solid.

Melting point: 143-146 ° C.

Ή-NMR (CDC / T S) δ (ppm):

 1.16 (s, 3H), 1.21 (s, 3H), 1.32 (s, 9H), 1.42-1.44 (m, 6H),

 1.73 (s, 3H), 1.80 (s, 3H), 1.92-1.98 (m, 1H), 2.20-2.71 (m, 11H),

3.61 (br, 1H), 3.68 (m, 4H), 4.05 (t, 1H, J = 7 Hz),

 4.10 (d, 1H, J = 7 Hz), 4.24 (d, 1H, J = 8 Hz), 4.33-4.38 (m, 2H),

4.56-4.60 (m, 2H), 5.00-5.13 (m, 4H), 5.24 (dd, 1H, J = 3, 20 Hz),

5.68-5.72 (m, 2H), 6.18 (t, 1H, J = 8 Hz), 7.27-7.47 (m, 7H),

7.58 (t, 1H, J = 8 Hz), 8.09 (d, 2H, J = 8 Hz).

MS-FAB: 981 (H ⁺ ). Industrial applicability

1 7 3 The following experimental examples show the antitumor effects of the compounds of the present invention.

Experimental example

Three tumor cells, P388, PC-6 and PC- 12, respectively, P388 is 5.0 × 10 ² cells / 1 50 1 / Ueru, PC- 6 is 5.0 × 10 ³ cells / 150 ^ 1 / Ueru, PC - 12 is The seeds were seeded at 1.0 × 10 cells / 150 1 / μl on a 96-μl microplate, and P388 was added 2 hours after the addition, and the other two were added 50 1 / μl after 24 hours. After culturing for 3 days, add 20 μl / ml of a 5 mg / ml solution of MTT [3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl-2H-tetrazolium promide]. did. Four hours later, the culture solution was removed, dimethyl sulfoxide was added in 150 1 well, and the absorbance was measured at 540 nm. Antitumor effect of the drug concentration to 50 ¾ of control group proliferation of drug addition group GI _5. The values (ng / ml) are shown in Table 1.

 table 1

P388 PC-6 PC-12 TAKI-SOTE 1.62 1.16 19.1 Example 1 0.433 0.5 0.824 Example 3 0.255 0.585 0.619 Example 5 0.306 0.281 0.549 Example 7 0.0159 0.0925 0.0782 Example 8 0.801 0.379 2.55 Example 10, 11 0.256 0.293 0.302 Example 12 0.197 0.29 0.205 Example 14 0.214 0.266 0.755 Example 25 0.125 0.224 0.234 Example 27 0.356 0.281 0.527 Example 29, 30 0.81 0.781 0.862

1 7 4

Claims

The scope of the claims

1. General formula (I)

[Where,

R ¹ represents a phenyl group, and the phenyl group may have, as a substituent, one or more groups selected from the group consisting of a halogen atom, an alkyl group and an alkoxyl group.

R ² represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an alkoxyl group, and these alkyl group, alkenyl group, alkynyl group, cycloalkyl group and alkoxyl group are a halogen atom, a hydroxyl group, a carboxyl group, an alkoxyl group. A group selected from the group consisting of a group, an aryloxy group, a phenyl group, an amino group, an alkylamino group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group as one or more substituents You may have one.

R ³ represents an amino group, a hydrogen atom, a hydroxyl group, a halogen atom, an alkoxyl group, an azido group or an acyloxy group having one or two substituents selected from the group consisting of an alkyl group and an acyl group.

R ⁴ is an amino group having one or two substituents as a substituent selected from the group consisting of an alkyl group and an acyl group, a hydrogen atom, a hydroxyl group, a halogen atom, an alkoxyl group,

1 7 5 Azido group or an acyloxy group, wherein the alkoxyl group and the alkoxyl group are a halogen atom, a hydroxyl group, a carboxyl group, a cycloalkyl group, an alkoxyl group, an aryl group, an aryloxy group, an amino group, an alkylamino group, an alkoxycarbonyl group; An aryloxycarbonyl group, an acyl group, an acylamino group, an acyloxy group, and a heterocyclic group (the heterocyclic group may have one or more alkyl groups on the constituent atoms of the ring) And may have one or more groups selected from the group consisting of

Also, R ³ and R ^{4 work} together to form

: Q

(In the formula, Q represents an oxygen atom, N—R ⁷ or CR ⁸ R ⁹ , and R ⁷ , R ⁸ and R ⁹ each independently represent an alkyl group or an acyl group.)

May be formed.

R ⁵ represents a methyl group,

Or may become connexion such together with R ^4, R ⁴ and each R ⁵ is taken together form 3-membered ring with the carbon atom bonded structure.

R ⁶ represents an alkyl group, an alkenyl group or an alkynyl group,

 These alkyl group, alkenyl group and alkynyl group include carboxyl group, alkoxyl group, aryloxy group, alkoxycarbonyl group, aryloxy group, cyano group, hydroxyl group, amino group, alkylamino group, acyl group, and acylamino group. Group, acyloxy group, alkoxycarbonylamino group, alkylthio group, alkylsulfinyl group, alkylsulfonyl group and formula

One N X

(X means oxygen atom, sulfur atom, CH ₂ , CH—Y, ΝΗ or Ν— 、, Υ

1 7 6 Represents an alkyl group. ) Represents a saturated or unsaturated heterocyclic group containing a nitrogen atom having a size of 3 to 8 members (the heterocyclic group is an alkyl group on a carbon atom which is a constituent atom of the ring). And may have one or more groups selected from the group consisting of as substituents.

Z ¹ represents a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group,

Z ² represents a hydrogen atom, a hydroxyl group, a halogen atom or an alkyl group,

Z ³ represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and these alkyl group, alkenyl group, alkynyl group, cycloalkyl group, aryl group and heterocyclic group represent a halogen atom , Hydroxyl, carboxyl, alkyl, alkoxyl, phenyl, amino, alkylamino, aminoalkyl, alkylaminoalkyl, alkoxycarbonyl, aryloxycarbonyl, acyl, acylamino, and alkoxy. It may have one or a plurality of groups selected from the group consisting of a group as a substituent.

Z ⁴ represents an alkyl group, an aryl group or an alkoxyl group, wherein the alkyl group, the aryl group and the alkoxyl group are a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxyl group, a phenyl group, an amino group, an alkylamino group, It may have, as a substituent, one or more groups selected from the group consisting of aminoalkyl groups, alkylaminoalkyl groups, alkoxycarbonyl groups, aryloxycarbonyl groups, acyl groups, acylamino groups and acyloxy groups. .

In addition,

The dotted line of the portion means that the bond of the portion may be a double bond. (Where R ³ is a hydrogen atom, R ⁴ is a hydrogen atom or a hydroxyl group, and the bond between the carbon atom to which R ³ is bonded and the carbon atom to which R ⁴ is bonded is a single bond. Excluded.) And its salts.

2. The compound or a salt thereof according to claim i, wherein Z ¹ and Z ² are a fluorine atom.

1 7 7

3. The compound according to claim 1, wherein Z ¹ is a hydroxyl group, and Z ² is a hydrogen atom.

4. a Zeta ¹ is hydroxyl group, the compounds and salts thereof according to claim 1, wherein Zeta ² is a methyl group.

5. Compounds and salts thereof according to claim 1, wherein Zeta ⁴ is Fuweniru group.

6. Compounds and salts thereof according to claim 1, wherein Zeta ⁴ is a tertiary butoxy group.

7. Compounds and salts thereof according to claim 1, wherein Zeta ³ is Fuweniru group.

8. The compounds and salts thereof according to claim 1 Symbol mounting a heterocyclic group of Zeta ³ monocyclic 5- or 6-membered ring size of.

9. Zeta ³ is the size of the 5-membered ring or 6-membered ring monocyclic, as a constituent atom of the ring structure, an oxygen atom, according to claim 1, wherein the heterocyclic group containing one nitrogen atom or a sulfur atom Compounds and salts thereof.

1 0. Zeta ³ is the size of the 5-membered ring or 6-membered ring monocyclic, as the constituent atoms of the ring structure is an oxygen atom, a nitrogen atom or a heterocyclic group of the sulfur atom one containing unsaturated A compound according to claim 1 and a salt thereof.

1 1. Zeta ³ is furyl group, compounds and salts thereof of claim 1, wherein a pyrrolyl group or a pyridyl group.

1 2. Zeta ³ Chikaraku 2-methyl - compound and its salt according to claim 1 which is 1-propenyl group.

13. The compound according to claim 1, wherein R ² is an alkyl group, and a salt thereof.

14. The compound according to claim 1, wherein R ² is a methyl group, an ethyl group, or a propyl group, and a salt thereof.

15. The compound according to claim 1, wherein R ² is an alkoxyl group, and a salt thereof.

16. The compound according to claim 1, wherein R ^{2 is a} methoxy group or an ethoxy group, and a salt thereof.

17. The compound according to claim 1, wherein R ² is a cycloalkyl group, and a salt thereof.

1 8. The compounds and salts thereof according to claim 1, wherein R ² is a cyclopropyl group.

1 9. R ³ and R ⁴ together

1 7 8

(In the formula, Q represents an oxygen atom, N—R ⁷ or CR ⁸ R ⁹ , and R ⁷ , R ⁸ and IT each independently represent an alkyl group or an acyl group.)

 2. The compound according to claim 1, represented by the general formula (I-11), and a salt thereof, which form a structure represented by

 20. The compound according to claim 19, wherein Q is an oxygen atom, and a salt thereof.

 twenty one.

2. The compound according to claim 1, which is represented by the general formula (I-12), wherein the bond at the dotted line is a double bond.

1 7 9

22. The compound according to claim 1, wherein R ⁴ is a fluorine atom, and a salt thereof.

23. The compound according to claim 1, wherein R ^{4 is a} methoxy group, and a salt thereof.

2 4. The compound according to claim 1, represented by the general formula (I-13), wherein R ⁴ and R ⁵ together form a three-membered ring together with the carbon atom to which they are bonded, and a salt thereof. .

2 5. R ⁶ is a substituent of formula I NX

1 8 0 (X represents an oxygen atom, a sulfur atom, CH ₂ , CH—Y, NH or N—Y, and Y represents an alkyl group.)

Represented by the formula, a saturated heterocyclic group containing a nitrogen atom having a size of a 5-membered ring or a 6-membered ring. 2. The compound according to claim 1, which is an alkyl group having 1 to 3 carbon atoms or an aryl group having the following formula:

26. R ⁶ has morpholine or thiomorpholine as the substituent (the morpholine or thiomorpholine may have one or more methyl groups on carbon atoms constituting the ring). 2. The compound according to claim 1, which is an alkyl group having 1 to 3 carbon atoms or an aryl group.

1 8 1