JP2006510626A - Epothilone analogs for site-specific delivery in the treatment of proliferative diseases - Google Patents

Abstract

Conjugates of epothilone and epothilone derivatives (as effectors) with appropriate saccharides or saccharide derivatives (as recognition units) are described. Their generation is performed by a recognition unit that is reacted with a suitable linker, and the resulting compound is conjugated to an effector. The pharmaceutical use of the conjugate to treat proliferative or angiogenesis-related processes is described.

Description

In the last decade, a series of highly effective new chemotherapeutic agents for the treatment of tumors have been developed. Despite all these efforts, treatment options and treatment windows are limited by the high intrinsic toxicity of these pharmaceutical agents.
Only a small portion of the dose of substance reaches the tumor (Anderson et al., Clin Pharmacokinet 27,191-201, 1994; Thorpe et al., Breast Canc Res Treat 36,237-251, 1995), where the highest amount of substance is healthy Ingested by the tissue and thus causes many undesired side effects.

  For this reason, selective release of systemically administered chemotherapeutic agents at the target site always provides a scientific challenge. Finally, recent developments are intended to detoxify cytostatic agents, for example by conversion to the prodrug form, and to break down non-toxic prodrugs only when tumors are reached by tumor-associated enzymes. Confirmation of this concept could be achieved by Bosslet (Bosslet et al., Canc Res 58, 1195-1201, 1998) in an example of a non-toxic prodrug based on doxorubicin chemically linked by glucuronic acid. In this case, the discovery that increased lysosomal β-D-glucuronidase activity was observed in the necrotic area of many tumors was used.

On the one hand, the relatively low cytotoxicity of the chemotherapeutic agent doxorubicin, which is used and requires high doses of prodrugs, has been found to be a drawback, and on the other hand, the relatively quick progression of resistance to doxorubicin itself is It turns out to be a drawback.
A new class of structures of epothilone and its analogs mainly offers the possibility of avoiding those drawbacks. Most natural or synthetically modified compounds from these types of structures exert their sufficient antiproliferative activity against most types of tumor cells that are resistant to other chemotherapeutic agents. To do. The degree of activity on these cells is over 10,000 times higher compared to chemotherapeutic agents used in clinical practice, such as taxol, doxorubicin, cis-platinum or camptothecin.

  Within the scope of the present invention, chemically highly sensitive and highly functionalized activities of epothilone and its analogues by different recognition units comprising saccharides or saccharide derivatives through different linkers at various positions of the active ingredient. The possibility of linking component types has now been found.

The object of the present invention is therefore based on the following:
1. Discovery of a method for linking highly active components from structural types of epothilones and epothilone derivatives through linkers with appropriate recognition units, so that the resulting conjugates can be chemically and metabolized for the development of pharmaceutical agents. Superior to basic epothilones or epothilone derivatives in terms of their therapeutic range, their selectivity of action and / or unwanted toxic side effects, and / or their activity intensity;
2. Synthesis of suitable linker recognition units;
3. Development of a method for linking these linker recognition units to conjugates using epothilone.
Accordingly, the present invention provides the following general formula:

[Wherein R ^1a , R ^1b are independently of each other hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, or together, a — (CH ₂ ) _m group (where m is 2-5 Is);
R ^2a and R ^2b, independently of one another, are hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, or taken together — (CH ₂ ) _n group (where n is 2 to 5), or C ₂ -C ₁₀ alkenyl or C ₂ -C ₁₀ alkynyl;
R ³ is hydrogen, C ₁ -C ₁₀ alkyl, aryl or aralkyl;
R ^4a and R ^4b are each independently hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, or together — (CH ₂ ) _p group, where p is 2-5. ;

R ⁵ is hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, C 0 ₂ H, C 0 ₂ alkyl, CH ₂ OH, CH ₂ 0 alkyl, CH ₂ 0 acyl, CN, CH ₂ NH ₂ , CH ₂ N ( Alkyl, acyl) _1,2 , or CH ₂ Hal;
Hal is a halogen atom;
R ⁶ and R ⁷ are in each case hydrogen, or an additional bond together, or an oxygen atom together, an NH group together, or an N-alkyl group together, or together. And CH ₂ group;
G is an oxygen atom or CH ₂ ;
DE is a group H ₂ C—CH ₂ , HC═CH, C≡C, CH (OH) —CH (OH), CH (OH) —CH ₂ , CH ₂ —CH (OH), the following groups:

O—CH ₂ or, when G represents a CH ₂ group, CH ₂ —O;
W is a group C (= X) R ⁸ , or a bi- or tricyclic aromatic or heteroaromatic group;
L ³ is hydrogen or, when the group in W contains a hydroxyl group, forms the group OL ⁴ with the latter, or when the group in W contains an amino group, the group NR ²⁵ -L ⁴ together with the latter Forming;
R ²⁵ is hydrogen or C ₁ -C ₁₀ alkyl;
X is an oxygen atom, or two OR ²⁰ groups, or a C ₂ -C ₁₀ alkylenedioxy group (should be linear or branched), or H / OR ⁹ , or a CR ¹⁰ R ¹¹ group ;
R ⁸ is hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, halogen or CN;
R ⁹ is hydrogen or a protecting group PG ^X ;

R ¹⁰ and R ^11, in each case, independently of one another, are hydrogen, C ₁ -C ₂₀ alkyl, aryl or aralkyl, or together with a methylene carbon atom, form a 5- to 7-membered carbocyclic ring. Forming;
Z may represent oxygen or H / OR ¹² ;
R ¹² can represent hydrogen or the protecting group PG ^Z
Alpha-Y is a group OC (= O), O- CH 2, CH 2 -C (= O), NR 21 -C (= O) or NR ²¹ may represent -SO _2;
R ²⁰ can represent C ₁ -C ₂₀ alkyl;
R ²¹ may represent a hydrogen atom or C ₁ -C ₁₀ alkyl;
PG ^X , PG ^Y and PG ^Z may represent the protecting group PG;

L ¹ , L ² , and L ⁴ each independently represent hydrogen, a group C (= O) Cl, a group C (= S) Cl, a group PG ^Y , or a linker recognition unit of the general formula (III) Wherein at least one substituent L ¹ , L ² or L ⁴ represents a linker recognition unit of general formula (III); said linker recognition unit of general formula (III) has the following structure:

Where
R ^22a and R ^22b each independently represent hydrogen, C ₁ -C ₂₀ alkyl, C ₁ -C ₂₀ acyl, C ₁ -C ₂₀ acyloxy, aryl, aralkyl, hydroxy, alkoxy, CO ₂ H, CO ₂ alkyl, Can represent halogen, CN, NO ₂ , NH ₂ or N ₃ ;
U ^{is, -C (= O) NR 23} -, -C (= S NR 23 -, -C (= O NR 23 -CH 2 -, -C (= S) NR 23 -CH 2 -, -C ( = O) O-, -C (= S) O-, -C (= O) O-CH _2- , -C (= S) O-CH _2- ;
R ²³ may represent hydrogen or C ₁ -C ₁₀ alkyl; and
EG represents the following general formula (IV):

Is a recognition unit represented by
R ²⁴ may represent the group CH ₂ 0PG ⁴ or the group CO ₂ R ²⁶ ;
PG ¹ , PG ² , PG ³ and PG ⁴ can independently represent hydrogen or the protecting group PG;
R ²⁶ is hydrogen, C ₁ -C ₂₀ alkyl, C ₁ -C ₂₀ alkenyl, C ₄ -C ₇ cycloalkyl (can contain an oxygen atom), aryl, aralkyl, tris (C ₁ -C ₂₀ alkyl) Silyl, bis (C ₁ -C ₂₀ alkyl) -arylsilyl, (C ₁ -C ₂₀ alkyl) -diarylsilyl, or tris (aralkyl) -silyl]
Or as a mixture of different isomers and / or as pharmaceutically acceptable salts thereof.

According to the present invention, the conjugate comprises one or more recognition units; in this case, the recognition units associated with the conjugate may be the same or different. Preferably, the recognition units of the conjugate are the same.
The compounds of general formula I are those α-, β- or γ-cyclodextrin inclusions, or their substituted α-, β- or γ-cyclodextrin inclusions, or liposomes or PEGylated It can be used in the form of a composition.
The conjugates of the invention are preferably used for the treatment of diseases associated with the growth process. For example, treatment of a wide variety of tumors, treatment of inflammation and / or neurodegenerative diseases such as multiple sclerosis or Alzheimer's disease, angiogenesis related diseases such as solid tumor growth, rheumatoid arthritis or fundus disease May be mentioned.

  Particularly preferred is the use of the conjugates of the invention for the treatment of primary tumors and / or metastases that are not surgically accessible as monotherapy or in combination with substances that induce cell death (apoptosis) and necrosis, As a result, when the cell degrades, it results in an increased release of lysosomal enzymes, such as glucuronidase, usually in the cell, which results in a strong response of the conjugate of the invention. For example, in this context, mention may be made of substances used for so-called “vascular targeting”. Those substances lead to destruction of the tumor endothelium, resulting in increased necrosis of the tumor due to incomplete nutrient supply. For example, an L19 structure such as EDB fibronectin or combrestatin A4-prodrug may be mentioned here.

  The production of epothilones, their precursors and derivatives of the general formula II is for example described in DE 19907588, WO 98/25929, WO 99/58534, WO 99/2514, WO 99/67252, WO 99/67253, WO 99/7692, EP 99/4915, WO 00/485, WO 00/1333, WO 00/66589, WO 00/49019, WO 00/49020, WO 00/49021, WO 00/71521, WO 00/37473, WO 00/57874, WO 01/92255, WO 01/81342, WO 01/73103, WO 01/64650, WO 01/70716, US 6204388, US 6387927, US 6380394, US 02/52028, US 02/58286, US 02/62030, WO It is carried out according to methods known to those skilled in the art as described in 02/32844, WO 02/30356, WO 02/32844, WO 02/14323, and WO 02/8440.

Alkyl groups R ^la , R ^lb , R ^2a R ^2b , R ³ , R ^4a , R ^4b , R ⁵ , R ⁸ , R ¹⁰ , R ¹¹ , R ²⁰ , R ²¹ , R ^22a , R ^22b R ²³ , R ²⁵ , R ²⁶ and R ²⁷ are linear or branched alkyl groups having 1 to 20 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, Heptyl, hexyl and decyl can be considered.

Alkyl groups R ^1a , R ^1b , R ^2a , R ^2b , R ³ , R ^4a , R ^4b , R ⁵ , R ⁸ , R ¹⁰ , R ¹¹ , R ²⁰ , R ²¹ , R ^22a R ^22b , R ²⁵ , R ²⁶ and R ²⁷ can also be perfluorinated or have 1 to 5 halogen atoms, hydroxyl groups, C ₁ -C ₄ -alkoxy groups, or C ₆ -C ₁₂ -aryl groups (1 to 3 Can be substituted by a halogen atom).

Aryl group R ^la , R ^lb , R ^2a , R ^2b , R ³ , R ^4a , R ^4b , R ⁵ , R ⁸ , R ¹⁰ , R ¹¹ , R ^22a , R ^22b , R ²⁶ and R ²⁷ as 1 or Substituted and unsubstituted carbocyclic or heterocyclic groups having multiple heteroatoms such as phenyl, naphthyl, furyl, thienyl, pyridyl, pyrazolyl, pyrimidinyl, oxazolyl, pyridazinyl, pyrazinyl, quinolyl, benzothiazolyl, benzoxazolyl (one or more places, halogen, OH, 0- alkyl, CO ₂ H, C0 ₂ - _{alkyl, -NH 2, -N0 2, -N} 3, -CN, C l -C 20 - alkyl, C ₁ - C ₂₀ - acyl, C _l -C ₂₀ - may be replaced by an acyloxy group) are suitable. Heteroatoms can be oxidized as a result of oxidation of pyridyl to pyridyl-N-oxide if aromatic properties are not lost.

Substituted and unsubstituted carbocyclic or heterocyclic groups having one or more heteroatoms as bi- and tricyclic aryl groups W, such as naphthyl, anthryl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolyl , Isoquinolyl, benzoxazinyl, benzofuranyl, indolyl, indazolyl, quinoxalinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, thienopyridinyl, pyridopyridinyl, benzopyrazolyl, benzotriazolyl or dihydroindolyl (halogen, OH at one or more positions) , 0-alkyl, CO ₂ H, C0 ₂ -alkyl, -NH ₂ , -N0 ₂ , -N ₃ , -CN, C _l -C ₂₀ -alkyl, C ₁ -C ₂₀ -acyl, C _l -C ₂₀ -Which may be substituted by an acyloxy group) is suitable. As a result, heteroatoms can be oxidized, such as the oxidation of quinolyl to quinolyl-N-oxide, if aromatic properties are not lost.

R ^1a , R ^lb , R ^2a , R ^2b , R ³ , R ^4a , R ^4b , R ⁵ , R ⁸ , R ¹⁰ , R ^ll , R ^22a , R ^22b , R ²⁶ and R ²⁷ are The ring can contain up to 14 C atoms, preferably 6 to 10 C atoms, and the alkyl chain can contain 1 to 8, preferably 1 to 4 atoms. Examples of aralkyl groups are benzyl, benzyl, phenylethyl, naphthylmethyl, naphthylethyl, furylmethyl, thienylethyl and pyridylpropyl. The ring may be halogen, OH, 0-alkyl, CO ₂ H, C 0 ₂ -alkyl, -N 0 ₂ , -N ₃ , -CN, C ₁ -C ₂₀ -alkyl, C ₁ -C at one or more positions. ₂₀ - acyl, C _l -C ₂₀ - it may be replaced by an acyloxy group.

Representative examples of the protecting group PG include tris (C ₁ -C ₂₀ alkyl) silyl, bis (C ₁ -C ₂₀ alkyl) -allylsilyl, (C ₁ -C ₂₀ alkyl) -diarylsilyl, tris (aralkyl) -silyl, C ₁ -C ₂₀ -alkyl, C ₂ -C ₂₀ -alkenyl, C ₄ -C ₇ -cycloalkyl (which can further contain an oxygen atom in the ring), aryl, C ₇ -C ₂₀ -aralkyl, C _1- C ₂₀ - acyl, aroyl, C ₁ -C ₂₀ - alkoxycarbonyl, C ₁ -C ₂₀ - alkylsulfonyl, and arylsulfonyl may be mentioned.

  As alkyl, silyl and acyl groups for the protecting group PG, in particular those groups known to the person skilled in the art are considered. Alkyl or silyl groups that are readily decomposable from their corresponding alkyl ethers and silyl ethers, such as methoxymethyl, methoxyethyl, ethoxyethyl, tetrahydropyranyl, tetrahydrofuranyl, trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenyl Silyl, tribenzylsilyl, triisopropylsilyl, benzyl, para-nitrobenzyl, or para-methoxybenzyl groups, and alkylsulfonyl and arylsulfonyl groups are preferred. A suitable example of an alkoxycarbonyl group is trichloroethyloxycarbonyl (Troc). Suitable acyl groups are, for example, formyl, acetyl, propionyl, isopropionyl, trichloromethylcarbonyl, pivalyl, and butyryl or benzoyl (which may be substituted by amino and / or hydroxy groups).

As amino protecting group PG, groups known to the person skilled in the art are considered. For example, mention may be made of the Alloc, Boc, Z, benzyl, f-Moc, Troc, Stabase or bene zostabase groups.
As halogen atoms, fluorine, chlorine, bromine or iodine are considered.
Acyl groups can contain 1 to 20 carbon atoms, whereby formyl, acetyl, propionyl, isopropionyl and pivalyl groups are preferred.
The C ₂ -C ₁₀ -alkylene α, ω-dioxy group possible for X is preferably an ethylene ketal or neopentyl ketal group.
Preferred recognition units EG are those that can be cleaved from the latter by overexpression of the appropriate enzyme in the growing tissue. For example, glucuronidase may be mentioned here.

Preferred compounds of general formula I are
AY represents OC (= O) or NR ²¹ -C (= O);
DE represents a H ₂ C—CH ₂ group or a HC═CH group;
G represents a CH ₂ group; Z represents an oxygen atom;
When R ^1a , R ^1b are individual, C ₁ -C ₁₀ alkyl, or together, a — (CH ₂ ) _p group (p is 2, 3 or 4);
R ^2a and R ^2b each independently represent hydrogen, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, or C ₂ -C ₁₀ alkynyl; R ³ represents hydrogen;
R ^4a and R ^4b each independently represent hydrogen or C ₁ -C ₁₀ alkyl;
R ⁵ represents hydrogen, C ₁ -C ₄ alkyl, CH ₂ OH, CH ₂ NH ₂ , CH ₂ N (alkyl, acyl) _1,2 or CH ₂ Hal;

R ⁶ and R ⁷ together represent an additional bond, together NH group, or N-alkyl group together, or CH ₂ group together, or oxygen atom together;
W is a group C (= X) R ⁸ , or 2-methylbenzothiazol-5-yl group, or 2-methylbenzoxazol-5-yl group, or quinolin-7-yl group, or 2-aminomethyl Represents a benzothiazol-5-yl group, or a 2-hydroxymethylbenzothiazol-5-yl group, or a 2-aminomethylbenzoxazol-5-yl group, or a 2-hydroxymethylbenzoxazol-5-yl group; ;

X represents a CR ¹⁰ R ¹¹ group; R ⁸ represents hydrogen, C ₁ -C ₄ alkyl, a fluorine atom, a chlorine atom, or a bromine atom;
R ¹⁰ / R ¹¹ is hydrogen / 2-methylthiazol-4-yl, or hydrogen / 2-pyridyl, or hydrogen / 2-methyloxazol-4-yl, or hydrogen / 2-aminomethylthiazol-4-yl, Or hydrogen / 2-aminomethyloxazol-4-yl, or hydrogen / 2-hydroxymethylthiazol-4-yl, or hydrogen / 2-hydroxymethyloxazol-4-yl.

In preferred embodiments, the groups R ^22a and R ^22b are C ₁ -C ₈ -alkyl, C ₁ -C ₈ -alkoxy, halogen, nitro, CN, N ₃ , NH ₂ , and CO _2- (C _1- Selected from the group consisting of (C ₈ -alkyl). In this regard, group methyl, ethyl, propyl, i- propyl, tert- _{butyl, CF 3, C 2 F 5} , F, Cl, _{nitro, CN, N 3, NH 2} , CO 2 - methyl, CO ₂ - ethyl , CO ₂ - propyl or CO _2-i-Puropuru is particularly preferred.

In another preferred embodiment, the group R ²⁶ is selected from the group consisting of C ₁ -C ₈ -alkyl and C ₂ -C ₈ -alkenyl. In this connection, the groups til, ethyl, propyl, i-propyl, t-butyl, CF ₃ , propenyl and butenyl are particularly preferred.
In another preferred embodiment, the groups R ^2a and R ^2b are such that one of the groups R ^2a or R ^2b represents hydrogen and in each case the other group is C ₁ -C ₇ -alkyl, C _2- Selected to be selected from the group consisting of C ₇ -alkenyl and C ₂ -C ₇ -alkynyl. In this connection, the groups methyl, ethyl, opyl, i-propyl, propenyl, butenyl, propynyl and butynyl are particularly preferred.

The compounds mentioned below are particularly preferred in the present invention as effector elements:
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-methyl-2- (2-methyl-thiazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-methyl-vinyl] -5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-methyl-vinyl]-4,8-dihydroxy-5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-methyl-2- (2 -Methyl-thiazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;

(1 S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-methyl-vinyl ] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(1 S, 3 S (E), 7S, 10R, 11S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-methyl-vinyl] -7, 11- Dihydroxy-8, 8,10, 12, 16-pentamethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-7-ethyl-5, 5,9, 13-tetramethyl-16- [1-methyl-2- (2- Methyl-thiazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-methyl-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-methyl-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;

(1 S, 3S (E), 7S, 1OR, ll S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [l-methyl-2 -(2-Methyl-thiazol-4-yl) -vinyl] -4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-methyl-vinyl] -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3 S (E), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-methyl-vinyl] -7, 11 -Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-fluoro-2- (2-methyl-thiazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-fluoro-vinyl] -5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-fluoro-vinyl] -4,8-dihydroxy-5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-fluoro-2- (2 -Methyl-thiazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-fluoro- Vinyl] -8, 8,10, 12, 16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 1OR, ll S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-fluoro-vinyl] -7, 11- Dihydroxy-8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5, 5,7, 9, 13-pentamethyl-16- [1-chloro-2- (2-methyl-thiazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-chloro-vinyl] -5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-chloro-vinyl] -4,8-dihydroxy-5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (Z), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-chloro-2- ( 2-Methyl-thiazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-chloro- Vinyl] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-chloro-vinyl] -7, 11 -Dihydroxy-8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-fluoro-2- (2- Methyl-thiazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -l-fluoro-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-fluoro-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [l-fluoro-2- ( 2-methyl-thiazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-fluoro-vinyl ] -10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;

(1 S, 3 S (Z), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-fluoro-vinyl] -7, 11 -Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-chloro-2- (2- Methyl-thiazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-chloro-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-chloro-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-chloro-2 -(2-Methyl-thiazol-4-yl) -vinyl] -4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;

(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-chloro-vinyl ] -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 1OR, ll S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-chloro-vinyl] -7, 11- Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-methyl-2- (2-pyridyl)- Vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-methyl-2- (2-pyridyl ) -Vinyl] -4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-methyl-2- (2- Pyridyl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;

(1S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-methyl-2- (2-pyridyl) -vinyl] -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-fluoro-2- (2-pyridyl)- Vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-fluoro-2- (2- Pyridyl) -vinyl] -4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-chloro-2- (2-pyridyl)- Vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-chloro-2- (2-pyridyl ) -Vinyl] -4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5, 9-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-fluoro-2- (2- Pyridyl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-fluoro-2- ( 2-pyridyl) -vinyl] -4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-chloro-2- (2- Pyridyl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-chloro-2- (2-pyridyl) -vinyl] -4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-methyl-2- (2-methyl-oxazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-methyl-vinyl] -5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-methyl-vinyl]-4,8-dihydroxy-5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (E), 7S, 10R, 11 S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-methyl-2- ( 2-Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-methyl-vinyl]- 8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, ll S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-methyl-vinyl] -7, 11- Dihydroxy-8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5, 9-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-methyl-2- (2- Methyl-oxazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-methyl-vinyl] -7- Ethyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-methyl-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-methyl-2 -(2-Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, ll S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-methyl-vinyl ] -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;

(1S, 3S (E), 7S, 10R, 11S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-methyl-vinyl] -7, 11-dihydroxy- 10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-fluoro-2- (2-methyl-oxazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-fluoro-vinyl] -5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-fluoro-vinyl] -4,8-dihydroxy-5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-fluoro-2- (2 -Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;

(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7,11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-fluoro-vinyl ] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-fluoro-vinyl] -7, 11- Dihydroxy-8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-chloro-2- (2-methyl-oxazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-chloro-vinyl] -5, 5, 7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-chloro-vinyl] -4,8-dihydroxy-5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;

(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-chloro-2- (2- Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5, 9-dione;
(1 S, 3 S (Z), 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-chloro- Vinyl] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(lS, 3S (Z), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-chloro-vinyl] -7, 11-dihydroxy -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-fluoro-2- (2- Methyl-oxazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-fluoro-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-fluoro-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [l-fluoro-2- (2-Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-fluoro-vinyl] -10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-fluoro-vinyl] -7, 11-dihydroxy -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-chloro-2- (2- Methyl-oxazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-chloro-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-chloro-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-chloro-2- ( 2-methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecan-5,9-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-chloro-vinyl] -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 1OR, ll S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-chloro-vinyl] -7, 11- Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;

(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [2- (2-methyl-thiazol-4-yl ) -Vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -vinyl] -5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-thiazol-4-yl) -vinyl] -4, 8-dihydroxy-5,5, 7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [2- (2-methyl-thiazole-4 -Yl) -vinyl] -4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -vinyl] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;

(1 S, 3 S (E), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -vinyl] -7, 11-dihydroxy-8 , 8,10,12,16-pentamethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [2- (2-methyl-thiazole- 4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -vinyl] -7-ethyl-5, 5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-thiazol-4-yl) -vinyl] -4, 8-dihydroxy-7-ethyl-5, 5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [2- (2-methyl -Thiazol-4-yl) -vinyl] -4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;

(1 S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7,11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -vinyl] -10-ethyl -8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -vinyl] -7, 11-dihydroxy-10- Ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-5,5, 7,9, 13-pentamethyl-16- [2- (2-pyridyl) -vinyl] -oxa Cyclohexadec-13-ene-2,6-dione;
(1S, 3S, (E), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [2- (2-pyridyl) -vinyl ] -4, 17-Dioxa-bicyclo [14. 1.0] Heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-Dihydroxy-7-ethyl-5, 5,9, 13-tetramethyl-16- [2- (2-pyridyl) -vinyl ] -Oxacyclohexadec-13-ene-2,6-dione;

(lS, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [2- (2-pyridyl ) -Vinyl] -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- (2-methyl-benzothiazol-5-yl) -oxacyclohexa Dec-13-ene-2, 6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -5,5, 7,9, 13-pentamethyl-oxacyclohex Sadec-13-ene-2, 6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-oxacyclohex Sadec-13-ene-2, 6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12, 16-pentamethyl-3- (2-methyl-benzothiazol-5-yl) -4 , 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;

(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -8,8, 10,12, 16- Pentamethyl-4,17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-8,8, 10,12, 16-pentamethyl -4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-ethyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-ethyl-5,5, 9,13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;

(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazol-5-yl ) -4,17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(lS, 3S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-ethyl-8, 8, 12, 16 -Tetramethyl-4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-10-ethyl-8, 8,12, 16- Tetramethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-propyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-propyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-propyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 125, 16R) -7, 11-Dihydroxy-10-propyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole- 5-yl) -4,17-dioxa-bicyclo [14.1.0] heptadecan-5,9-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7,11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-propyl-8, 8,12, 16- Tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7, 11-dihydroxy-10-propyl-8, 8,12 , 16-tetramethyl-4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-butyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-butyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-butyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7,11-Dihydroxy-10-butyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazol-5-yl ) -4,17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-butyl-8, 8,12, 16 -Tetramethyl-4,17-dioxa-bicyclo [14. 1.0] -heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7, 11-dihydroxy-10-butyl-8, 8,12 , 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-Dihydroxy-7-allyl-5, 5,9,13-tetramethyl-16- (2-methyl-benzothiazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8 S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-allyl-5,5, 9, 13-tetra Methyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-allyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-10-allyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole- 5-yl) -4,17-dioxa-bicyclo [14.1. 0] heptadecane-5, 9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-allyl-8, 8, 12, 16 -Tetramethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;

(1 S, 3 S, 7S, 10R, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-10-allyl-8, 8,12 , 16-Tetramethyl-4,17-dioxa-bicyclo [14.1. 0] Heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-prop-2-ynyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-prop-2-ynyl-5, 5,9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-prop-2-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-prop-2-ynyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole -5-yl) -4,17-dioxa-bicyclo (14.1.0) heptadecane-5,9-dione;

(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-prop-2-ynyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-10-prop-2-ynyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-but-3-enyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-but-3-enyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-but-3-enyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;

(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-but-3-enyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole -5-yl) -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-but-3-enyl-8 , 8, 12, 16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-10-but-3-enyl-8, 8 , 12,16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-but-3-ynyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-but-3-ynyl-5, 5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-but-3-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-but-3-ynyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole -5-yl) -4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, ll S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-but-3-ynyl-8 , 8,12, 16-Tetramethyl-4,17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7, 11-dihydroxy-10-but-3-ynyl-8, 8 , 12,16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- (2-methyl-benzoxazol-5-yl) -oxacyclohexa Dec-13-ene-2, 6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl)-5,5, 7,9, 13-pentamethyl-oxacyclohex Sadec-13-ene-2, 6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-oxacyclohex Sadec-13-ene-2, 6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12, 16-pentamethyl-3- (2-methyl-benzoxazol-5-yl) -4 , 17-Dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, ll S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -8,8, 10,12, 16 -Pentamethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-8,8, 10,12, 16- Pentamethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5, 9-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-ethyl-5,5, 9,13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazol-5-yl ) -4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 10R, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-ethyl-8, 8,12 , 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;

(1S, 3S, 7S, 1OR, ll S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16 -Tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-propyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-propyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-propyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-propyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazole-5 -Yl) -4,17-dioxa-bicyclo [14.1. 0] heptadecan-5,9-dione;

(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-propyl-8, 8,12 , 16-Tetramethyl-4,17-dioxa-bicyclo [14.1. 0] Heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 10R, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7,11-dihydroxy-10-propyl-8, 8,12 , 16-tetramethyl-4,17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-butyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-butyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-butyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;

(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-butyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazol-5-yl ) -4,17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-butyl-8, 8,12 , 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7,11-dihydroxy-10-butyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-allyl-5, 5,9, 13-tetramethyl-16- (2-methyl-benzoxazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-allyl-5,5, 9,13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-allyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-allyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazol-5-yl ) -4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-allyl-8, 8,12 , 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5, 9-dione;
(1 S, 3S, 7S, 10R, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-10-allyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-prop-2-ynyl-5,5, 9,13-tetramethyl-16- (2-methyl-benzoxazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-prop-2-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8 S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-prop-2-ynyl-5, 5,9 , 13-Tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-prop-2-ynyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benz Oxazol-5-yl) -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-prop-2-ynyl-8 , 8,12, 16-Tetramethyl-4,17-dioxa-bicyclo [14. 1.0] Heptadecane-5, 9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-10-prop-2-ynyl-8, 8 , 12,16-Tetramethyl-4,17-dioxa-bicyclo [14. 1. 0] -heptadecane-5, 9-dione;

(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-but-3-enyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-but-3-enyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-but-3-enyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-but-3-enyl-8, 8,12, 16-tetramethyl-3- (2-methyl- Benzoxazol-5-yl) -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-but-3-enyl-8, 8 , 12,16-Tetramethyl-4,17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;

(1 S, 3 S, 7S, 10R, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7,11-dihydroxy-10-but-3-enyl-8 , 8,12,16-Tetramethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-but-3-ynyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-but-3-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-but-3-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-but-3-ynyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazole -5-yl) -4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9 dione;

(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-but-3-ynyl-8, 8 , 12,16-Tetramethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9 dione;
(1 S, 3 S, 7S, 1 OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-10-but-3-ynyl- 8, 8, 12, 16-Tetramethyl-4,17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione.
In the compounds of the general formula (I) according to the invention comprising one of the elements described above, the hydrogen atom in the element is replaced by the group L ¹ -L ^{3 at the} position shown in formula (I), wherein And the groups L ¹ -L ³ have the meanings indicated above.

The present invention also provides the following formula (III ¹ )

[Wherein RG ¹ represents an O═C═N group, or an S═C═N group, or an O═C═N—CH ₂ group, or an S = C═N═CH ₂ group; and
R ^22a , R ^22b and EG have the meanings recited in claim 1]
A linker recognition unit represented by:

The following formula (III ² ):

[Wherein RG ² represents a HO—CH ₂ group or HNR ²³ —CH ₂ ; and
R ^22a , R ^22b and EG have the meanings recited in claim 1]
A linker recognition unit represented by the formula (wherein the following compound:
(4-hydroxymethyl) phenyl-2,3,4,6-tetra-0-acetyl-α-D-galactopyranoside;
(2-hydroxymethyl) phenyl-2,3,4,6-tetra-0-acetyl-α-D-galactopyranoside;
(4-hydroxymethyl) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester;
(2-hydroxymethyl) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester;
(4-hydroxymethyl) phenyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside;

(2-hydroxymethyl-4-nitro) phenyl-2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside;
(4-hydroxymethyl-2-nitro) phenyl-2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside;
(2-hydroxymethyl-4-nitro) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester;
(4-hydroxymethyl-2-nitro) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester;
(2-chloro-4-hydroxymethyl) phenyl-2,3,4,6-tetra-0-acetyl-α-D-galactopyranoside;
(2-chloro-4-hydroxymethyl) does not contain phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester); or

The following formula (III ³ ):

[Wherein, RG ³ represents a Hal-C (= O) -CH ₂ group, a Hal-C (= S) -CH ₂ group, or R ²⁷ -C (= O) -OC (= O) -CH ₂ Group, or R ²⁷ —C (═O) —OC (═S) —CH ₂ group, or the following formula:

Or a group represented by the following formula:

Represents a group represented by:
R ²⁷ is C ₁ -C ₁₀ -alkyl, aryl or aralkyl; and
R ^22a , R ^22b and EG have the meanings recited in claim 1]
A linker recognition unit represented by the formula (wherein the following compound:
2,5-dioxopyrrolidin-1-yl- [4- (2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl) -benzyl] carbonate;
2,5-dioxopyrrolidin-1-yl- [2- (2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl) -benzyl] carbonate;
2,5-dioxopyrrolidin-1-yl- [4-((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) -methyluronate) benzyl] carbonate;
4-nitrophenyl- [2-((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) methyluronate) -benzyl] carbonate;
2,5-dioxopyrrolidin-1-yl- [4- (2,3,4,6-tetra-0-acetyl-β-D-glucopyranosyl) -benzyl] carbonate;

4-nitrophenyl- [2- (2,3,4,6-tetra-0-acetyl-α-D-galactopyranosyl) -5-nitrobenzyl] carbonate;
4-nitrophenyl- [2-((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) methyluronate) -5-nitrobenzyl] carbonate;
4-nitrophenyl- [4-methoxy-5-nitro-2- ((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) methyluronate) benzyl] carbonate;
4-nitrophenyl- [4- ((2, 3, 4-tri-0-acetyl-β-D-glucopyranosyl) methyluronate) -5-nitrobenzyl] carbonate;
It also relates to 4-chlorophenyl- [2- ((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) methyluronate) -5-nitrobenzyl] carbonate free).

The invention also relates to the following method:
Method for reacting a linker recognition unit of the general formula III ¹ with a compound of the general formula I, wherein the conditions in which at least one group L ¹ , L ² or L ⁴ represents a linker recognition unit do not have to be fulfilled And L ¹ and / or L ² and / or L ⁴ have the meaning of a hydrogen atom, and free hydroxyl and / or amino groups that are not required for the reaction are optionally protected;
Method for reacting a linker recognition unit of general formula III ² with a compound of general formula I, wherein the conditions in which at least one group L ¹ , L ² or L ⁴ represents a linker recognition unit do not have to be fulfilled And L ¹ and / or L ² and / or L ⁴ have the meaning of a C (═O) Hal group or C (═S) Hal group and are not required for the reaction free hydroxyl groups and / or The amino group is optionally protected;
A method for reacting a linker recognition unit of general formula III ³ with a compound of general formula I, wherein the conditions in which at least one group L ¹ , L ² or L ⁴ represents a linker recognition unit do not have to be fulfilled And L ¹ and / or L ² and / or L ⁴ have the meaning of a hydrogen atom, and free hydroxyl groups and / or amino groups that are not required for the reaction are optionally protected.

The present invention also provides a compound represented by the general formula (I) (wherein the substituents have the above-mentioned meanings, provided that at least one substituent L ¹ , L ² or L ⁴ represents the linker recognition unit of the general formula (III)). The conditions to represent need not be fulfilled and the use of at least one substituent L ¹ , L ² or L ⁴ represents hydrogen, the group C (═O) Cl or the group C (═S) Cl) in the above process Also related.
The present invention also provides a compound represented by the general formula (I) (wherein the substituents have the above-mentioned meanings, provided that at least one substituent L ¹ , L ² or L ⁴ represents the linker recognition unit of the general formula (III)). The conditions to represent need not be met, and the effector recognition unit conjugate of at least one substituent L ¹ , L ² or L ⁴ represents hydrogen, the group C (═O) Cl or the group C (= S) Cl) It also relates to its use for body generation.

The present invention also relates to the use of linker recognition units of general formula III ¹ , III ² or III ³ for the production of effector recognition unit conjugates as described above.
The present invention also relates to the use of a linker recognition unit of general formula III ¹ , III ² or III ³ in one of the methods of the present invention for the production of effector recognition unit conjugates as described above. .
The invention also relates to a conjugate of the invention comprising an effector, a linker and a recognition unit for use as a medicament or for the production of a medicament or pharmaceutical composition.

The invention also relates to diseases associated with the proliferative process such as tumors, inflammation and / or neurodegenerative diseases, multiple sclerosis, Alzheimer's disease treatment, or angiogenesis related diseases such as solid tumor growth, rheumatoid arthritis or It also relates to the use of the conjugate of the invention for the production of a medicament for the treatment of fundus diseases.
The present invention is also directed to the generation of drugs for the treatment of primary tumors and / or metastases that are not surgically accessible, either as monotherapy or in combination with substances that strongly induce cell death (apoptosis) and necrosis. As a result, when tumor cells degrade, it results in an increased release of normal intracellular lysosomal enzymes, such as glucuronidase, which results in a strong response of the conjugate.

  In this case, the treatment or administration in combination with the above substances, the simultaneous administration of the individual components in the combination (in a mixture and in separate doses), or separate administration, for example alternating administration, and administration schemes are included. Where one component is given as a long-term drug and the other component is further administered at regular or irregular intervals over a short period of time. In this case, the components in the combination are supplied through the same route or different routes. In the combined administration, those in which the components in the combination achieve an additive action are preferred; those administration schemes in which a synergistic action is set are particularly preferred.

  With regard to combination administration with the conjugates of the invention, mention may be made of substances used for so-called “vascular targeting”. These substances lead to destruction of the tumor endothelium, in particular, resulting in increased necrosis of the tumor due to an incomplete supply of nutrients. For example, an L19 structure such as EDB-fibronectin or combbrestatin A4-prodrug may be mentioned here.

Example of synthesis of a linker recognition unit (LE):
Example LE1: (2S, 3S, 4S, 5R, 6S) -3,4,5-Triacetoxy-6- (4-hydroxymethyl-2-nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:

Example LE1 a: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-triacetoxy-6- (4-formyl-2-nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester :
A solution of 5.0 g (12.6 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester in 9 ml of acetonitrile Is mixed with 2.1 g of 4-hydroxy-3-nitrobenzaldehyde, 3.58 g of silver (I) oxide and it is stirred at 23 ° C. for 16 hours. It is passed through celite and the residue obtained after removal of the solvent is purified by chromatography on silica gel. 5.7 g (11.8 mmol, 94%) of the title compound are obtained.

Example LE1: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Triacetoxy-6- (4-hydroxymethyl-2-nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester :
In a mixture of 110 ml tetrahydrofuran and 22 ml methanol, a solution of 5.72 g (11.8 mmol) of the compound obtained according to Example LE1a is mixed with 224 mg sodium borohydride at 0 ° C. and it is stirred for 30 minutes. It is mixed with saturated ammonium chloride solution, diluted with water and extracted several times with ethyl acetate. The combined organic extracts are washed with saturated sodium chloride solution, dried over sodium sulfate, and the residue obtained after filtration and removal of the solvent is purified by chromatography on fine silica gel. 5.62 g (11.6 mmol) 98%) of the title compound is isolated.
¹ H-NMR (d ₆ -DMSO): δ = 1.99 + 2.02 (9H), 3.64 (3H), 4.51 (2H), 4.73 (1H), 5.07 (1H), 5.12 (1H), 5.43 (1H ), 5.48 (1H), 5.71 (1H), 7.38 (1H), 7.62 (1H), 7.80 (1H) ppm.

Example LE2: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Triacetoxy-6- (2-hydroxymethyl-4-nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester :

Example LE2a: (2S, 3S, 4S, 5R, 6S) -3,4,5-triacetoxy-6- (2-formyl-4-nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
Similar to Example LE1a, 5.0 g (12.6 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester Is reacted with 2-hydroxy-3-nitrobenzaldehyde and, after processing and purification, 4.31 g (8.92 mmol, 71%) of the title compound is isolated.

Example LE2: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Triacetoxy-6- (2-hydroxymethyl-4-nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester :
Analogously to Example LE1, 1.0 g (2.07 mmol) of the compound obtained according to Example LE2a is reacted and, after processing and purification, 921 mg (1.90 mmol, 92%) of the title compound is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 2.06 (3H), 2.08 (3H), 2.10 (3H), 2.53 (1H), 3.71 (3H), 4.25 (1H), 4.61 (1H), 4.72 (1H) , 5.27-5. 44 (4H), 7.09 (1H), 8. 18 (1H), 8.30 (1H) ppm.

Example LE3: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (2-hydroxymethyl-4-nitro-phenoxy) -tetrahydro- Pyran-2-carboxylic acid allyl ester:

Example LE3 a: 2- [1, 3] Dioxolan-2-yl-4-nitro-phenol:
A solution of 25 g (149.6 mmol) of 2-hydroxy-5-nitrobenzaldehyde in 500 ml of toluene is mixed with 100 ml of ethylene glycol, 2.85 g of p-toluenesulfonic acid monohydrate, and Reflux for 5 hours in a water separator. After cooling, it is poured into saturated sodium hydrogen carbonate solution and extracted several times with ethyl acetate, the combined organic extracts are washed with saturated sodium chloride solution and dried over sodium sulfate. The residue obtained after filtration and removal of the solvent is reacted without further purification.

Example LE3b: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Triacetoxy-6- (2- [1, 3] dioxolan-2-yl-4-nitro-phenoxy)-tetrahydro-pyran -2-carboxylic acid methyl ester:
20.0 g (50.4 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester is obtained according to Example LE3a The compound is reacted analogously to Example LE1a and, after processing and purification, 21.9 g (41.5 mmol, 82%) of the title compound is isolated.

Example LE3c: (2S, 3S, 4S, 5R, 6S) -6- (2- [1, 3] dioxolan-2-yl-4-nitro-phenoxy) -3, 4,5-trihydroxy-tetrahydro-pyran -2-carboxylic acid methyl ester:
A solution of 21.85 g (41.5 mmol) of the compound obtained according to Example LE3b in 1.17 L of methanol is mixed at 0 ° C. with a solution of 2.42 g of sodium methanolate in 45 ml of methanol and it is added over 3 hours. , Stir. It is mixed with 9.14 g of citric acid hydrate and concentrated by evaporation. The residue is dissolved in a mixture consisting of ethyl acetate and methanol, filtered over a short silica gel layer and 16.6 g (41.4 mmol, 99%) of the title compound is isolated after removal of the solvent.

Example LE3d: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (2- [1,3] dioxolan-2-yl-4 -Nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
A solution of 8.0 g (19.9 mmol) of the compound obtained according to Example LE3c in 560 ml of dichloromethane is mixed with 22.9 ml of tert-butyl-dimethyl-silyl triflate and 23.8 ml of 2,6-lutidine and Is stirred for 24 hours at 23 ° C. It is poured into water and extracted several times with dichloromethane, the combined organic extracts are washed with saturated sodium chloride and dried over magnesium sulfate. After filtration and removal of the solvent, the resulting residue was purified by chromatography on fine silica gel and 9.90 g (13.3 mmol, 67%) of the title compound and 2.17 g (29.2 mmol, 15%) The stereoisomer of is isolated.

Example LE3e: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (2- [1, 3] dioxolan-2-yl- 4-Nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid:
A solution of 5.64 g (7.53 mmol) of the compound obtained according to Example LE3d in 150 ml of allyl alcohol is mixed with 9.1 ml of a 1M solution of sodium allyl alcoholate in allyl alcohol and it is stirred at 50 ° C. for 2.5 hours. Stir. It is concentrated by evaporation, mixed with water, extracted several times with dichloromethane, the combined organic extracts are washed with saturated sodium chloride solution and dried over magnesium sulfate. After filtration and removal of the solvent, the resulting residue was purified by chromatography on fine silica gel and 1.7 g (2.44 mmol, 32%) of the title compound and 1.87 g (2.43 mmol, 32% ) (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (2- [1, 3] dioxolan-2-yl-4 -Nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid allyl ester is isolated.

Example LE3f: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (2- [1,3] dioxolan-2-yl- 4-Nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
A solution of 1.35 g (1.85 mmol) of the compound obtained according to Example LE3e in 5 ml of dimethylformamide is combined with 0.3 ml of 1,8-diazabicyclo [5.4.0] undec-7-ene and 0.176 ml of allyl bromide. Mix and stir it at 23 ° C. for 16 hours. It is poured into water and extracted several times with ethyl acetate, the combined organic extracts are washed with saturated sodium chloride solution and dried over magnesium sulfate. After filtration and removal of the solvent, the resulting residue is purified by chromatography on fine silica gel and 1.03 g (1.34 mmol, 72%) of the title compound is isolated.

Example LE3g: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (2-formyl-4-nitro-phenoxy) -tetrahydro- Pyran-2-carboxylic acid allyl ester:
A solution of 50 mg (61.6 μmol) of the compound obtained according to Example LE3f in 2 ml of acetone is mixed with 12.9 mg of p-toluenesulfonic acid monohydrate and it is stirred at 23 ° C. for 24 hours. It is poured into saturated sodium bicarbonate solution, extracted several times with ethyl acetate, the combined organic extracts are washed with saturated sodium chloride solution and dried over magnesium sulfate. After filtration and removal of the solvent, the resulting residue is purified by chromatography on fine silica gel and 25.9 mg (35.7 μmol, 58%) of the title compound is isolated.

Example LE3: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (2-hydroxymethyl-4-nitro-phenoxy) -tetrahydro -Pyran-2-carboxylic acid allyl ester:
720 mg (0.99 mmol) of the compound obtained according to Example LE3 g are reacted analogously to Example LE1 and, after processing, further reaction without purification, 710 mg (0.975 mmol, 98%) of the title compound Is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 0.05-0. 15 (18H), 0.85-0. 94 (27H), 2.97 (1H), 3.87 (1H), 3.99 (1H), 4.36 (1H), 4.41 (1H), 4.52 (1H), 4.58 (2H), 5.01 (1H), 5.22 (1H), 5.28 (1H), 5.61 (1H), 5.85 (1H), 7.07 (1H), 8.18 (1H), 8.33 (1H) ppm.

Example LE4: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-hydroxymethyl-2-nitro-phenoxy) -tetrahydro -Pyran-2-carboxylic acid allyl ester:

Example LE4a: 4- [1,3] Dioxolan-2-yl-2-nitro-phenol:
Analogously to Example LE3a, 25 g (149.6 mmol) of 4-hydroxy-3-nitrobenzaldehyde are reacted and, after processing, 27.6 g (131 mmol, 87%) of the title compound is isolated.

Example LE4b: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Triacetoxy-6- (4- [1, 3] dioxolan-2-yl-2-nitro-phenoxy)-tetrahydro-pyran -2-carboxylic acid methyl ester:
23.4 g (59.0 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester was obtained according to Example LE4a The compound is reacted analogously to Example LE1a and after processing and purification, 24.5 g (46.4 mmol, 79%) of the title compound is isolated.

Example LE4c: (2S, 3S, 4S, 5R, 6S) -6- (4- [1, 3J Dioxolan-2-yl-2-nitro-phenoxy) -3, 4, 5-trihydroxy-tetrahydro-pyran- 2-carboxylic acid methyl ester:
358 mg (679 μmol) of the compound obtained according to Example LE4b are reacted analogously to Example LE3c and, after processing, 270 mg (673 μmol, 99%) of the title compound are isolated.

Example LE4d: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4- [1,3] dioxolan-2-yl-2 -Nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
268 mg (668 μmol) of the compound obtained according to Example LE4c are reacted analogously to Example LE3d and, after processing and purification, 183 mg (246 μmol, 37%) of the title compound are isolated.

Example LE4e: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4- [1,3] dioxolan-2-yl-2 -Nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid:
A solution of 5.0 g (6.72 mmol) of the compound obtained according to Example LE4d in 130 ml of methanol is mixed with 3.6 ml of water, heated to 70 ° C. and 3.01 ml of 1,8-diazabicyclo [5.4.0. Mix with undec-7-ene. It is reacted for more than 4 hours, set at pH 3 by adding 1N hydrochloric acid and extracted several times with ethyl acetate. The combined organic extracts are washed with water and saturated sodium chloride solution and dried over sodium sulfate. After filtration and removal of the solvent, the resulting residue is purified by chromatography on fine silica gel and 1.53 g (2.10 mmol, 31%) of the title compound is isolated.

Example LE4f: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tet-butyl-dimethyl-silanyloxy) -6- (4- [1, 3] dioxolan-2-yl-2 -Nitro-phenoxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
2.84 g (3.93 mmol) of the compound obtained according to Example LE4e are reacted analogously to Example LE3f and, after processing and purification, 2.51 g (3.26 mmol, 83%) of the title compound is isolated.

Example LE4g: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-formyl-2-nitro-phenoxy) -tetrahydro- Pyran-2-carboxylic acid allyl ester:
2.51 g (3.26 mmol) of the compound obtained according to Example LE4f is reacted analogously to Example LE3g and reacted after processing without further purification, 2.35 g (3.24 mmol, 99%) of the title The compound is isolated.

Example LE4: (2S, 3S, 4S, 5R, 6S) -3,4,5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-hydroxymethyl-2-nitro-phenoxy) -tetrahydro- Pyran-2-carboxylic acid allyl ester:
2.23 g (3.07 mmol) of the compound obtained according to Example LE4 g are reacted analogously to Example LE1 and, after processing and purification, 2.12 g (2.91 mmol, 95%) of the title compound is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 0.00 (3H), 0.07 (3H), 0.12-0. 17 (12H), 0.83 (9H), 0.87 (9H), 0.92 (9H), 1.83 (1H), 3.85 (1H), 4.05 (1H), 4.40 (1H), 4.51 (1H), 4.60 (2H), 4.70 (2H), 5.22 (1H), 5.30 (1H), 5.58 (1H), 5.87 (1H), 7.17 (1H), 7.52 (1H), 7.83 (1H) ppm.

Example LE5: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-hydroxymethyl-phenoxy) -tetrahydro-pyran-2 -Carboxylic acid allyl ester:

Example LE5a: (2S, 3S, 4S, 5R, 6S) -3,4,5-Triacetoxy-6- (4-formyl-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
44.1 g (111 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester was replaced with 14 g of 4-hydroxy- React with benzaldehyde analogously to Example LE1a and, after processing and purification, 35.1 g (80 mmol, 72%) of the title compound is isolated.

Example LE5b: (2S, 3S, 4S, 5R, 6S) -3,4,5-triacetoxy-6- (4-hydroxymethyl-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
16.5 g (37.7 mmol) of the compound obtained according to Example LE5a are reacted analogously to Example LE1 and, after processing, reacted without further purification, 17.4 g (up to 37.7 mmol) of the title compound Isolate.

Example LE5c: (2S, 3S, 4S, 5R, 6S) -3,4,5-trihydroxy-6- (4-hydroxymethyl-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
17.4 g (maximum 37.7 mmol) of the compound obtained according to Example LE5b are reacted analogously to Example LE3c and reacted after processing without further purification 13.9 g (maximum 37.7 mmol) of the title compound Is isolated.

Example LE5d: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-tert-butyl-dimethyl-silanyloxymethyl-phenoxy ) -Tetrahydro-pyran-2-carboxylic acid methyl ester:
13.9 g (up to 37.7 mmol) of the compound obtained according to Example LE5c are reacted analogously to Example LE3d and after processing and purification 21.5 g (27.9 mmol, 74%) of the title compound are isolated .

Example LE5e: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-tert-butyl-dimethyl-silanyloxymethyl-phenoxy ) -Tetrahydro-pyran-2-carboxylic acid allyl ester:
A solution of 21.5 g (27.9 mmol) of the compound obtained according to Example LE5d in 103 ml of allyl alcohol is mixed with 9.9 ml of titanium (IV) -tetraisopropoxide and it is added under an atmosphere of anhydrous argon. Heat to 110 ° C. for 21 hours. After cooling, it is mixed with water, filtered over celite by dilution with ethyl acetate and the organic phase is separated. The aqueous phase is extracted several times with ethyl acetate, the combined organic extracts are washed with saturated sodium chloride solution and it is dried over sodium sulfate. After filtration and removal of the solvent, 22.6 g (up to 27.9 mmol) of the title compound is isolated without further purification.

Example LE5: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-hydroxymethyl-phenoxy) -tetrahydro-pyran-2 -Carboxylic acid allyl ester:
In a mixture consisting of 445 ml dichloromethane and 218 ml methanol, a solution of 22.6 g (max 27.9 mmol) of the compound obtained according to Example LE5e is mixed with 6.47 g camphor-10-sulfonic acid at 0 ° C. and Stir at 0 ° C. for 1.5 hours. It is mixed with saturated sodium hydrogen carbonate solution, diluted with water, extracted several times with dichloromethane, and the combined organic extracts are dried over sodium sulfate. After filtration, solvent removal and purification, 14.4 g (21.0 mmol, 75%) of the title compound is isolated.
¹ H-NMR (CDC1 ₃ ): δ = -0. 02 (3H), 0.07 (3H), 0.12 (3H), 0.14 (3H), 0.17 (6H), 0.85 (9H), 0.88 (9H), 0.92 (9H), 1.56 (1H), 3.86 (1H), 3.98 (1H), 4.37 (1H), 4.54 (1H), 4.62 (4H), 5.22 (1H), 5.31 (1H), 5.55 (1H), 5.89 (1H), 6.95 (2H), 7.28 (2H) ppm.

Example LE6: (2S, 3S, 4S, 5R, 6S) -4-Hydroxy-3,5-bis-triisopropylsilanyloxy-6- (4-hydroxymethyl-2-chloro-phenoxy) -tetrahydro-pyran -2-carboxylic acid allyl ester:

Example LE6a: 2-Chloro-4- [1,3] dioxolan-2-yl-phenol:
26.1 g (130 mmol, 81%) of the title compound reacted with 25 g (160 mmol) of 3-chloro-4-hydroxybenzaldehyde analogously to Example LE3a and reacted after processing without further purification Is isolated.

Example LE6b: (2S, 3S, 4S, 5R, 6S) -6- (2-Chloro-4- [1,3] dioxolan-2-yl-phenoxy) -3, 4,5-tris-acetoxy-tetrahydro -Pyran-2-carboxylic acid methyl ester:
29.1 g (73.3 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester are obtained according to Example LE6a React with 14.9 g of compound analogously to Example LE1a and, after processing and purification, 11.7 g (22.6 mmol, 31%) of the title compound is isolated.

Example LE6c: (2S, 3S, 4S, 5R, 6S) -6- (2-Chloro-4- [1,3] dioxolan-2-yl-phenoxy) -3,4,5-tris-hydroxy-tetrahydro- Pyran-2-carboxylic acid methyl ester:
25.3 g (48.9 mmol) of the compound obtained according to Example LE6b are reacted analogously to Example LE3c and, after processing, further reacted without purification, 17.2 g (44.0 mmol, 90%) The title compound is isolated.

Example LE6d: (2S, 3S, 4S, 5R, 6S) -6- (2-Chloro-4- [1,3] dioxolan-2-yl-phenoxy) -4-hydroxy-3,5-bis-triisopropyl Silanyloxy-tetrahydro-pyran-2-carboxylic acid methyl ester:
17.2 g (44.0 mmol) of the compound obtained according to Example LE6c is reacted analogously to Example LE3d by use of trifluoromethanesulfonic acid-triisopropylsilyl ester, and after processing and purification, 18.1 g (25.7 mmol) Mol, 58%) of the title compound is isolated.

Example LE6e: (2S, 3S, 4S, 5R, 6S) -6- (2-Chloro-4- [1,3] dioxolan-2-yl-phenoxy) -4-hydroxy-3,5-bistriisopropylsilanyl Oxy-tetrahydro-pyran-2-carboxylic acid:
A solution of 18.1 g (25.8 mmol) of the compound obtained according to Example LE6d in 400 ml of methanol is mixed with 13.9 ml of water, 7.7 ml of 1,8-diazabicyclo [4.5.0] undec-7-ene. And it is stirred at 70 ° C. for 4 hours. It is concentrated by evaporation, diluted with ethyl acetate and water, set to pH 2 with 4N hydrochloric acid, the separated organic phase is dried over sodium sulfate and, after filtration and removal of the solvent, the residue obtained Is purified by chromatography. 12.2 g (17.7 mmol, 69%) of the title compound is isolated.

Example LE6f: (2S, 3S, 4S, 5R, 6S) -6- (2-Chloro-4- [1,3] dioxolan-2-yl-phenoxy) -4-hydroxy-3,5-bistriisopropylsila Nyloxy-tetrahydro-pyran-2-carboxylic acid allyl ester:
12.2 g (17.7 mmol) of the compound obtained according to Example LE6e are reacted analogously to Example LE3f and after processing and purification 12.9 g (17.7 mmol, 100%) of the title compound are isolated.

Example LE6g: (2S, 3S, 4S, 5R, 6S) -6- (2-Chloro-4-formyl-phenoxy) -4-hydroxy-3, 5-bis-triisopropylsilanyloxy-tetrahydro-pyran-2 -Carboxylic acid allyl ester:
12.9 g (17.7 mmol) of the compound obtained according to Example LE6f is reacted analogously to Example LE3g and after processing 12.0 g (17.5 mmol, 99%) of the title compound is isolated and purified. Don't, let it react further.

Example LE6: (2S, 3S, 4S, 5R, 6S) -4-Hydroxy-3,5-bis-triisopropylsilanyloxy-6- (4-hydroxymethyl-2-chloro-phenoxy) -tetrahydro-pyran -2-carboxylic acid allyl ester:
12.0 g (17.5 mmol) of the compound obtained according to Example LE6f are reacted analogously to Example LE1 and after processing and purification 11.4 g (16.6 mmol, 95%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 0.98-1.31 (42H), 1.64 (1H), 2.43 (1H), 3.67 (1H), 4.03 (1H), 4.10 (1H), 4.26 (1H), 4.54-4. 64 (4H), 5.16-5. 31 (3H), 5.84 (1H), 7.02 (1H), 7.19 (1H), 7.39 (1H) ppm.

Example LE7: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-hydroxymethyl-2-methoxy-phenoxy) -tetrahydro- Pyran-2-carboxylic acid allyl ester:

Example LE7a: (2S, 3S, 4S, 5R, 6S) -3,4,5-triacetoxy-6- (4-formyl-2-methoxy-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
Variant 1 :
8.0 g (20.1 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester was added to 3.1 g of 4- React with hydroxy-3-methoxybenzaldehyde analogously to Example LE1a and after processing and purification, 3.2 g (6.8 mmol, 34%) of the title compound is isolated.

Variant 2 :
A solution of 5.0 g (12.6 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester in 150 ml of toluene Is mixed with 20 g of 4-hydroxy-3-methoxybenzaldehyde, 30 ml of 5N potassium hydroxide solution, 5.0 g of tetrabutylammonium hydrogen sulfate and the mixture is stirred at 23 ° C. for 2 days. It is mixed with ethyl acetate and water, the organic phase is separated and the aqueous phase is extracted several times with ethyl acetate. The combined organic extracts are washed with saturated sodium chloride solution, dried over sodium sulfate, and after filtration and removal of the solvent, the resulting residue is purified by chromatography. 1.94 g (4.14 mmol, 33%) of the title compound is isolated.

Example LE7b: (2S, 3S, 4S, 5R, 6S) -3,4,5-triacetoxy-6- (4-hydroxymethyl-2-methoxy-phenoxy) -tetrahydropyran-2-carboxylic acid methyl ester:
5.55 g (11.9 mmol) of the compound obtained according to Example LE7a is reacted analogously to Example LE1 and, after processing and purification, 3.67 g (7.80 mmol, 66%) of the title compound is isolated.

Example LE7c: (2S, 3S, 4S, 5R, 6S) -3,4,5-trihydroxy-6- (4-hydroxymethyl-2-methoxy-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester :
5.25 g (11.2 mmol) of the compound obtained according to Example LE7b are reacted analogously to Example LE3c, and after processing 4.64 g (up to 11.2 mmol) of the title compound are isolated without purification. Let it react further.

Example LE7d: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-tert-butyl-dimethyl-silanyloxymethyl-2 -Methoxy-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
4.64 g (up to 11.2 mmol) of the compound obtained according to Example LE7c are reacted analogously to Example LE3d and, after processing and purification, 8.43 g (10.5 mmol, 94%) of the title compound are isolated. .

Example LE7e: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-tert-butyl-dimethyl-silanyloxymethyl-2 -Methoxy-phenoxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
8.43 g (10.5 mmol) of the compound obtained according to Example LE7d is reacted analogously to Example LE5e and, after processing, 8.38 g (10.1 mmol, 96%) of the title compound is isolated and purified. Don't, let it react further.

Example LE7: (2S, 3S, 4S, 5R, 6S) -3,4,5-tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-hydroxymethyl-2-methoxy-phenoxy) -tetrahydro -Pyran-2-carboxylic acid allyl ester:
8.38 g (10.1 mmol) of the compound obtained according to Example LE7e are reacted analogously to Example LE5 and, after processing and purification, 5.92 g (8.3 mmol, 82%) of the title compound is isolated.
¹ H-NMR (CDC1 ₃ ): δ = -0.04 (3H), 0.06 (3H), 0.12 (3H), 0.13 (3H), 0.16 (3H), 0.21 (3H), 0.84 (9H), 0.87 (9H ), 0.92 (9H), 1.59 (1H), 3.82 (3H), 3.86 (1H), 4.01 (1H), 4.37 (1H), 4.52 (1H), 4.61 (4H), 5.21 (1H), 5.30 (1H ), 5.52 (1H), 5.89 (1H), 6.83 (1H), 6.90 (1H), 6.92 (1H) ppm.

Example LE8: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-hydroxymethyl-2-fluoro-phenoxy) -tetrahydro -Pyran-2-carboxylic acid allyl ester:

Example LE8a: (2S, 3S, 4S, 5R, 6S) -3,4,5-Triacetoxy-6- (4-formyl-2-fluoro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
14.2 g (35.8 mmol) of (2S, 3S, 4S, 5S, 6S) -3,4,5-triacetoxy-6-bromo-tetrahydro-pyran-2-carboxylic acid methyl ester was added to 5.05 g of 3- React with fluoro-4-hydroxybenzaldehyde analogously to Example LE1a and, after processing and purification, 13.3 g (29.1 mmol, 81%) of the title compound is isolated.

Example LE8b: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Triacetoxy-6- (4-hydroxymethyl-2-fluoro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester :
13.3 g (29.1 mmol) of the compound obtained according to Example LE8a are reacted analogously to Example LE1 and after processing 13.3 g (29.0 mmol, 100%) of the title compound is isolated and purified. Don't, let it react further.

Example LE8c: (2S, 3S, 4S, 5R, 6S) -3,4,5-trihydroxy-6- (4-hydroxymethyl-2-fluoro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
11.2 g (29.0 mmol) of the compound obtained according to Example LE8b is reacted analogously to Example LE3c and, after processing, 11.2 g (maximum 29.0 mmol) of the title compound is isolated without purification. Let it react further.

Example LE8d: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-tert-butyl-dimethyl-silanyloxymethyl- 2-Fluoro-phenoxy) -tetrahydro-pyran-2-carboxylic acid methyl ester:
11.2 g (up to 29.0 mmol) of the compound obtained according to Example LE8c are reacted analogously to Example LE3d and after processing and purification 18.5 g (23.4 mmol, 81%) of the title compound are isolated .

Example LE8e: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-tert-butyl-dimethyl-silanyloxymethyl-2 -Fluoro-phenoxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
18.5 g (23.4 mmol) of the compound obtained according to Example LE8d are reacted analogously to Example LE5e and, after processing, 18.6 g (22.8 mmol, 97%) of the title compound is isolated and purified. Don't, let it react further.

Example LE8: (2S, 3S, 4S, 5R, 6S) -3,4, 5-Tris- (tert-butyl-dimethyl-silanyloxy) -6- (4-hydroxymethyl-2-fluoro-phenoxy) -tetrahydro- Pyran-2-carboxylic acid allyl ester:
18.6 g (22.8 mmol) of the compound obtained according to Example LE8e are reacted analogously to Example LE5 and, after processing and purification, 13.3 g (19.0 mmol, 83%) of the title compound is isolated.
¹ H-NMR (CDCl ₃ ): δ = -0.02 (3H), 0.07 (3H), 0.12 (3H), 0.13 (3H), 0.17 (3H), 0.19 (3H), 0.84 (9H), 0.88 (9H ), 0.92 (9H), 1.62 (1H), 3.86 (1H), 4.01 (1H), 4.38 (1H), 4.53 (1H), 4.61 (4H), 5.22 (1H), 5.31 (1H), 5.55 (1H ), 5.90 (1H), 7.00 (1H), 7.02 (1H), 7.10 (1H) ppm.

Example of synthesis of effector-linker recognition unit (ELE):
Example ELE1: (2S, 3S, 4S, 5R, 6S) -3,4, 5-triacetoxy-6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- Hydroxy-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl ] -2-Nitro-phenoxy} -tetrahydro-pyran-2-carboxylic acid methyl ester:

Example ELE I a: (4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- (tert-butyl-dimethyl-silanyloxy) -4-hydroxy-5, 5,9, 13-tetramethyl- 16- (2-Methyl-benzothiazol-5-yl) -oxacyclohexadec-13-en-2,6-dione:
6.0 g (7.93 mmol) of (4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4 produced analogously to the method described in WO00 / 66589 in 186 ml of anhydrous dichloromethane , 8-Bis (tert-butyl-dimethyl-silanyloxy) -5,5,9,13-tetramethyl-16- (2-methyl-benzothiazol-5-yl) -oxacyclohexadec-13-ene-2 The solution of 6-dione is mixed at 0 ° C. with 26.4 ml of a 20% solution of trifluoroacetic acid in dichloromethane and it is stirred at 0 ° C. for 6 hours. It is poured into saturated sodium bicarbonate solution and extracted with dichloromethane, the combined organic extracts are washed with water and dried over magnesium sulfate. After filtration and removal of the solvent, the resulting residue is purified by chromatography on silica gel. 3.32 g (5.17 mmol, 65%) of the title compound is isolated as an unemployed solid.

Example ELE1b: (4S, 7R, 8S, 9S, 13Z, 16S) -chloroformate-7-allyl-8- (tert-butyl-dimethyl-silanyloxy) -5,5, 9, 13-tetramethyl-16- ( 2-Methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yl ester:
A solution of 1.0 g (1.56 mmol) of the compound obtained according to Example ELE1a in 20 ml of dichloromethane is mixed at 0 ° C. with a solution of 285 mg of triphosgene in 6 ml of dichloromethane, 160 μl of pyridine, and then at 23 ° C. Stir for 2.5 hours. It is concentrated by evaporation, the residue is taken up in ethyl acetate, washed with water and saturated sodium chloride solution and dried over magnesium sulphate. After filtration and removal of the solvent, the resulting residue is purified by chromatography on fine silica gel. 1.08 g (1.53 mmol, 98% of the title compound is isolated.

Example ELE1c: (2S, 3 S, 4S, 5R, 6S) -3,4, 5-triacetoxy-6- {4-[(4S, 7R, 8S, 9S, 13Z, 16S) 7-allyl-8- (tert-Butyldimethyl-silanyloxy) -5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxooxacyclohexadec-13-ene- 4-yloxycarbonyloxymethyl] -2-nitro-phenoxy} -tetrahydropyran-2-carboxylic acid methyl ester:
A solution of 1.08 g (1.53 mmol) of the compound obtained according to Example ELE1b in 30 ml of dichloromethane is mixed with 4.0 g of the compound obtained according to Example LE1 in 277 ml of triethyl and the suspension at 23 ° C. Stir for 16 hours. It is filtered, concentrated by evaporation and the residue is purified by chromatography on fine silica gel. 408 mg (354 μmol, 23%) of the title compound is isolated.

Example ELE2: (2S, 3S, 4S, 5R, 6S) -3,4, 5-triacetoxy-6- {4- [1S, 3S, 7S, 10R, 11S, 12S, 16R) -10-allyl-11 -Hydroxy-8,8, 12, 16-tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4,17-dioxa-bicyclo [14.1. 0] heptadec-7 -Iloxycarbonyloxymethyl] -2-nitro-phenoxy} -tetrahydro-pyran-2-carboxylic acid methyl ester:
A solution of 61 mg (58.7 μmol) of the compound obtained according to Example ELE1 in 2 ml of dichloromethane is mixed at −50 ° C. with 1.2 ml of a 0.1M solution of dimethyldioxiram in acetone and stirred for 1 hour. To do. It is poured into semi-concentrated sodium thiosulfate solution, extracted several times with dichloromethane, and the combined organic extracts are washed over sodium sulfate. After filtration and removal of the solvent, the resulting residue is purified by chromatography on a thin analytical plate.

29 mg (27.5 μmol, 47%) of the title compound and 10 mg (9.5 μmol 16%) of (2S, 3S, 4S, 5R, 6S) -3,4,5-triacetoxy 6- {4- [1R , 3S, 7S, 10R, 11S, 12S, 16S) -10-allyl-11-hydroxy-8,8,12,16-tetramethyl 3- (2-methyl-benzothiazol-5-yl) -5, 9 -Dioxo-4,17-dioxa-bicyclo [14.1.0] Heptadec-7-yloxycarbonyloxymethyl] -2-nitro-phenoxy} -tetrahydro-pyran-2-carboxylic acid methyl ester is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.03 (3H), 1.13 (3H), 1.16 (3H), 1.31 (3H), 1.34-1. 88 (7H), 2.06 (6H), 2.12 (3H), 2.16-2. 57 (6H), 2.71 (1H), 2.79 (3H), 2.84 (1H), 3.44 (1H), 3.69 (1H), 3.73 (3H), 4.22 (1H), 4.50 (1H), 4.71 (1H), 4.99-5. 05 (2H), 5.19 (1H), 5.25- 5.39 (3H), 5.45 (1H), 5.75 (1H), 6.07 (1H), 7.27 (2H), 7.32 (1H), 7.53 (1H), 7.78 (1H), 7.89 9 (1H) ppm.

Example ELE3: (2S, 3S, 4S, 5R, 6S) -3,4, 5-triacetoxy-6- {2- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- Hydroxy-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl ] -4-Nitro-phenoxy} -tetrahydro-pyran-2-carboxylic acid methyl ester:

Example ELE3a: (2S, 3S, 4S, 5R, 6S) -3,4, 5-triacetoxy-6- {2- [(4S, 7R, 8S, 9S, 13Z, 16S) 7-allyl-8- ( tert-butyl-dimethyl-silanyloxy) -5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-ene- 4-yloxycarbonyloxymethyl] -4-nitro-phenoxy} -tetrahydro-pyran-2-carboxylic acid methyl ester:
Analogously to Example ELE1c, 265 mg (376 μmol) of the compound obtained according to Example ELE1b are reacted with the compound obtained according to Example LE1 and, after processing and purification, 180 mg (156 μmol, 42%) of the title compound Is isolated.

Example ELE3: (2S, 3S, 4S, 5R, 6S) -3,4, 5-triacetoxy-6- {2- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- Hydroxy-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl ] -4-Nitro-phenoxy} -tetrahydro-pyran-2-carboxylic acid methyl ester:
Analogously to Example ELE1, 173 mg (150 μmol) of the compound obtained according to Example ELE3a are reacted and, after processing and purification, 58 mg (55.8 μmol, 37%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.00 (3H), 1.12 (3H), 1.13 (3H), 1.02-2.55 (13H), 1.70 (3H), 2.04 (3H), 2.07 (6H), 2.68 (1H), 2.76 (3H), 2.97 (1H), 3.39 (1H), 3.71 (1H), 3.73 (3H), 4.25 (1H), 4.65 (1H), 4.84 (1H), 5.00 (1H), 5.04 (1H), 5.16-5. 38 (5H), 5.51 (1H), 5.72 (1H), 5.97 (1H), 7.08 (1H), 7.35 (1H), 7.79 (1H), 7.92 (1H), 7.98 (1H) ppm.

Example ELE4: (2S, 3S, 4S, 5R, 6S) -3,4, 5-triacetoxy-6- {2-[(1S, 3S, 7S, 10R, 11S, 12S, 16R) -10-allyl -11-Hydroxy-8,8, 12, 16-tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14.1. 0] heptadec -7-yloxycarbonyloxymethyl] -4-nitro-phenoxy} -tetrahydro-pyran-2-carboxylic acid methyl ester:
Analogously to Example ELE2, 151 mg (145 μmol) of the compound obtained according to Example ELE3 are reacted and, after processing and purification, 75 mg (71.1 μmol, 49%) of the title compound and 28 mg (26.5 μmol). 18%) (2S, 3 S, 4S, 5R, 6S) -3,4, 5-triacetoxy 6- {2-[(1R, 3S, 7S, 10R, 11S, 12S, 16S) -10- Allyl-11-hydroxy-8,8,12,16-tetramethyl 3- (2-methyl-benzothiazol-5-yl) -5,9-dioxo-4,17-dioxa-bicyclo [14.1.0] heptadec -7-yloxycarbonyloxymethyl] -4-nitro-phenoxy} -tetrahydro-pyran-2-carboxylic acid methyl ester is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.03 (3H), 1.08-1.84 (6H), 1.12 (3H), 1.17 (3H), 1.32 (3H), 2.07 (3H), 2.08 (6H), 2.08-2. 17 (3H), 2.28-2. 57 (4H), 2.71 (1H), 2.79 (3H), 2.84 (1H), 3.43 (1H), 3.71 (1H), 3.73 (3H), 4.27 ( 1H), 4.74 (1H), 4.81 (1H), 5.01 (1H), 5.05 (1H), 5.24-5.43 (5H), 5.73 (1H), 6.04 (1H), 7.11 (1H), 7.28 (1H ), 7.80 (1H), 7.86 (1H), 8.03 (1H), 8.15 (1H) ppm.

Example ELE5: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-nitro-phenoxy}- 3, 4, 5-trihydroxytetrahydro-pyran-2-carboxylic acid:

Example ELE5a: (2S, 3 S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- (tert-butyl-dimethyl-silanyloxy ) -5,5, 9, 13-Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl ] -2-Nitro-phenoxy} -3,4,5-tris- (tert-butyl-dimethyl-silanyloxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
Analogous to Example ELE1c, 230 mg (312 μmol) of the compound obtained according to Example ELE1b are reacted with the compound obtained according to Example LE4 and, after processing and purification, 132 mg (95 μmol, 30%) of the title compound Is isolated.

Example ELE5: (2S, 3S, 4S, 5R, 6S) -6- {4-[(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-nitro-phenoxy}- 3, 4, 5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
In a mixture consisting of 6.4 ml of tetrahydrofuran and acetonitrile, respectively, a solution of 315 mg (226 μmol) of the compound obtained according to Example ELE5a is mixed with 3.2 ml of hexafluorosilicic acid, 3.2 ml of HF-pyridine complex and Stir at 23 ° C. for 16 hours. It is poured into saturated ammonium bicarbonate solution and extracted several times with ethyl acetate. The combined organic extracts are washed with saturated sodium chloride solution, dried over sodium sulfate, and after filtration and removal of the solvent, the resulting residue is purified by chromatography on fine silica gel. 116 mg (124 μmol, 55%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.02 (3H), 1.13 (3H), 1.16 (3H), 1.31-2.75 (19H), 2.78 (3H), 2.91 (1H), 3.40 (1H ), 3.71 (1H), 3.79 (2H), 3.94 (1H), 4.08 (1H), 4.60 (1H), 4.72 (2H), 4.75 (1H), 4.95-5.09 (3H), 5.16 (1H) , 5.28 (1H), 5.36 (1H), 5.55 (1H), 5.71 (1H), 5.86-6.00 (2H), 7.21 (2H), 7.34 4 (1H), 7.54 (1H), 7.74 ( 1H), 7.91 (1H) ppm.

Example ELE6: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, lOR, 11S, 12S, 16R) -10-allyl-l l-hydroxy-8, 8,12, 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14. 1.0] Heptadec-7-yloxycarbonyloxy Methyl] -2-nitro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE2, 50 mg (53 μmol) of the compound obtained according to Example ELE5 are reacted and, after processing and purification, 26 mg (27 μmol, 51%) of the title compound and 7 mg (7 μmol, 14 %) (2S, 3S, 4S, 5R, 6S) -6- {4-[(1R, 3S, 7S, 10R, 11 S, 12S, 16S) -10-allyl-l-hydroxy-8, 8 , 12,16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14. 1.0] Heptadec-7-yloxycarbonyloxymethyl ] -2-Nitro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester is isolated.

Example ELE7: (2S, 3S, 4S, 5R, 6S) -6- {4- [(lS, 3S, 7S, 10R, 1 lS, 12S, 16R) -10-allyl-l l-hydroxy-8, 8 , 12,16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14. 1.0] -heptadec-7-yloxycarbonyloxy Methyl] -2-nitro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid:
A solution of 26 mg (27 μmol) of the compound obtained according to Example ELE6 in 0.7 ml of dichloromethane is mixed with 1 mg of tetrakis-triphenylphosphine-palladium (0), 4 μl of pyrrolidine and it is stirred at 23 ° C. for 1 Stir for hours. It is mixed with 300 μl of 5% aqueous acetic acid, extracted with dichloromethane, washed with water and saturated sodium chloride solution and dried over sodium sulfate. After filtration and removal of the solvent, the residue obtained is purified by chromatography and 13.4 mg (15 μmol, 54%) of the title compound is isolated.
¹ H-NMR (CD ₃ 0D): δ = 1.04 (3H), 1.11 (3H), 1.25 (3H), 1.33 (3H), 1.40-1.83 (7H), 2.12 (2H), 2.37 (1H) , 2.58-2. 85 (3H), 2.83 (3H), 2.99 (1H), 3.44-3. 60 (5H), 3.77 (2H), 4.64 (1H), # 4. 95-5.07 (4H), 5.46 (1H), 5.77 (1H), 6.06 (1H), 7.33-7. 45 (3H), 7.63 (1H), 7.86 (1H), 7.94 (1H) ppm.

Example ELE8: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -2-nitro-phenoxy}- 3, 4, 5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:

Example ELE8a: (4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4- (tert-butyl-dimethyl-silanyloxy) -8-hydroxy-5, 5,9, 13-tetramethyl-16- (2-Methyl-benzothiazol-5-yl) -oxacyclohexadec-13-en-2,6-dione:
5.3 g (7.01 mmol) of (4S, 7R, 8S, 9S, 13Z, 16S) produced analogously to the method described in WO00 / 66589 in a mixture consisting of 85 ml of tetrahydrofuran and 85 ml of acetonitrile -7-allyl-4,8-bis (tert-butyl-dimethyl-silanyloxy) -5,5,9,13-tetramethyl-16- (2-methyl-benzothiazol-5-yl) -oxacyclohexadec The solution of -13-ene-2,6-dione is mixed with 31.7 ml of hexafluorosilicic acid, cooled to 0 ° C., 8.1 ml of trifluoroacetic acid are added dropwise, and the mixture is stirred at 0 ° C. for 20 hours. Stir.

It is poured into water, neutralized by adding saturated sodium hydrogen carbonate and extracted several times with ethyl acetate. The combined organic extracts are washed with saturated sodium chloride and dried over magnesium sulfate, and after filtration and removal of the solvent, the resulting residue is purified by chromatography on fine silica gel, 2.82 g (4.39 mmol, 63%) of the title compound is isolated as an unemployed solid.
¹ H-NMR (CDC1 ₃ ): δ = -0. 09 (3H), 0.08 (3H), 0.84 (9H), 1.08 (3H), 1.10 (3H), 1.12 (3H), 1.21-1. 86 ( 5H), 1.70 (3H), 2.15 (1H), 2.29-2.97 (8H), 2.84 (3H), 3.14 (1H), 3.96 (1H), 4.03 (1H), 4.97-5.06 (2H) , 5.23 (1H), 5.61 (1H), 5.77 (1H), 7.35 (1H), 7.79 (1H), 7.93 (1H) ppm.

Example ELE8b: (4S, 7R, 8S, 9S, 13Z, 16S) -chloroformate-7-allyl-4- (tert-butyl-dimethyl-silanyloxy) -5,5, 9, 13-tetramethyl-16- ( 2-Methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yl ester:
Analogously to Example ELE1b, 1.0 g (11.56 mmol) of the compound obtained according to Example ELE8a is reacted and 1.05 g (1.49 mmol, 96%) of the title compound is isolated.

Example ELE8c: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4- (tert-butyl-dimethyl-silanyloxy) -5,5, 9, 13-Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -2-Nitro-phenoxy} -3, 4, 5-tris- (tert-butyl-dimethyl-silanyloxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE1c, 250 mg (350 μmol) of the compound obtained according to Example ELE8b are reacted with 1.63 g of the compound obtained according to Example LE4 and, after processing and purification, 260 mg (186 μmol, 53%) The title compound is isolated.

Example ELE8: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -2-nitro-phenoxy}- 3, 4, 5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE5, 321 mg (230 μmol) of the compound obtained according to Example ELE8c are reacted and, after processing and purification, 77 mg (82 μmol, 36%) of the title compound is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.02 (3H), 1.06 (3H), 1.24 (3H), 1.38-2.00 (7H), 1.70 (3H), 2.27-2.45 (4H), 2.50 (2H), 2.85 (4H), 2.96-3. 49 (3H), 3.54 (1H), 3.77 (2H), 3.94 (1H), 4.05 (2H), 4.73 (2H), 4.89-5. 01 (3H ), 5.09-5. 25 (4H), 5.29 (1H), 5.38 (1H), 5.70 (1H), 5.84 (1H), 5.93 (1H), 7.34 (1H), 7.40 (1H), 7.60 (1H) , 7.79 (1H), 7.92 (1H), 7.98 (1H) ppm.

Example ELE9: (2S, 3 S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, 1 OR, ll S, 12S, 16R) -10-allyl-7-hydroxy-8, 8,12, 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4,17-dioxabicyclo [14. 1.0] Heptadec-11-yloxycarbonyloxy Methyl] -2-nitro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE2, 82 mg (87 μmol) of the compound obtained according to Example ELE8 are reacted and, after processing and purification, 57 mg (60 μmol, 69%) of the title compound and 8 mg (8.4 μmol, 10%) (2S, 3 S, 4S, 5R, 6S) -6- {4-[(RS, 3S, 7S, 10R, 11 S, 12S, 16S) -10-allyl-7-hydroxy-8, 8,12, 16-Tetramethyl 3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxio-4,17-dioxabicyclo [14. 1.0] Heptadec-11-yloxycarbonyloxymethyl ] -2-Nitro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester is isolated.

Example ELE 10: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1 S, 3S, 7S, 1 OR, 1 lS, 12S, 16R) -10-allyl-7-hydroxy-8 , 8,12,16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5,9-dioxo-4, 17-dioxa-bicyclo [14.1.0] heptadec-11-yloxycarbonyl Oxymethyl] -2-nitro-phenoxy} -3,4,5-trihydroxytetrahydropyran-2-carboxylic acid:
A solution of 57 mg (60 μmol) of the compound obtained according to Example ElE9 in 1.8 ml of dichloromethane is mixed little by little with 14.8 μl of phenylsilane, a total of 2.9 mg of tetrakis-triphenylphosphine palladium (0) and Stir at 23 ° C. for 19 hours. It is concentrated by evaporation, the resulting residue is purified by chromatography and 27 mg (30 μmol, 49%) of the title compound is isolated.
¹ H-NMR (DMSO-d ₆ ): δ = 0.91 (3H), 0.93 (3H), 1.07-2.75 (15H), 1.17 (3H), 1.23 (3H), 2.80 (3H), 2.93 (1H ), 3.08-3. 48 (4H), 3.61 (1H), 4.06 (1H), 4.87 (1H), 4.92 (1H), 4.99 (2H), 5.06 (1H), 5.14-5. 25 (4H), 5.67 (1H), 5.96 (1H), 7.44 (1H), 7.48 (1H), 7.65 (1H), 7.90 (1H), 7.99 (2H) ppm.

Example ELE11: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -phenoxy} -3, 4, 5-Trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:

Example ELE1la: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- (tert-butyl-dimethyl-silanyloxy) -5,5, 9, 13-Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -Phenoxy} -3, 4, 5-tris- (tert-butyl-dimethyl-silanyloxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
A solution of 1.7 g (2.41 mmol) of the compound obtained according to Example ELE1b in 51 ml of triene is mixed with 10.7 g of compound obtained according to Example LE5, 210 mg of sodium hydrogen carbonate and it is stirred at 23 ° C. for 16 hours. , Stir. It is filtered, concentrated by evaporation and the residue is purified by chromatography on fine silica gel. 1.95 g (0.44 mmol, 60%) of the title compound is isolated.

Example ELE11: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -phenoxy} -3, 4, 5-Trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
A solution of 1.95 g (1.44 mmol) of the compound obtained according to Example ELE11a in 87 ml of tetrahydrofuran is mixed in portions with a total of 7 ml of HF-pyridine complex over a period of several hours and is added at 23 ° C. for a total of 24 Stir for hours. It is poured into saturated ammonium bicarbonate solution and extracted several times with ethyl acetate.

The combined organic extracts are washed with saturated sodium chloride solution, dried over sodium sulfate, and after filtration and removal of the solvent, the resulting residue is purified by chromatography on fine silica gel. 766 mg (857 μmol, 59%) of the title compound is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.01 (3H), 1.13 (6H), 1.18-1.89 (6H), 1.69 (3H), 2.18-2.54 (5H), 2.57 (1H), 2.66 (1H), 2.79 (3H), 2.88 (1H), 3.23 (1H), 3.36 (1H), 3.41 (1H), 3.66-3. 95 (5H), 4.01 (1H), 4.56 (1H), 4.64- 4. 78 (3H), 4.93 (1H), 5.01 (1H), 5.05 (1H), 5.14 (1H), 5.26 (1H), 5.34 (1H), 5.57 (1H), 5.72 (1H), 5.84-5 97 (2H), 6.81 (2H), 6.94 (2H), 7.34 (1H), 7.74 (1H), 7.86 (1H) ppm.

Example ELE12: (2S, 3S, 4S, 5R, 6S) -6- {4- [(lS, 3S, 7S, 10R, 11S, 12S, 16R) -10-allyl-11-hydroxy-8, 8,12 , 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14. 1.0] -heptadec-7-yloxycarbonyloxymethyl] -Phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE2, 766 mg (857 μmol) of the compound obtained according to Example ELE11 are reacted and, after processing and purification, 616 mg (677 μmol, 79%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.03 (3H), 1.11 (3H), 1.19 (3H), 1.31 (3H), 1.23-1. 83 (6H), 1.96 (2H), 2.30-2. 58 (4H), 2.68 (1H), 2.79 (1H), 2.81 (3H), 3.39-3.93 (1OH), 4.61- 4.79 (5H), 5.02 (1H), 5.06 (1H), 5.26 (1H), 5.34 (1H), 5.43 (1H), 5.72 (1H), 5.88 (1H), 5.97 (1H), 6.84 (2H), 7.05 (2H), 7.26 (1H), 7.76 (1H), 7.84 (1H) ppm .

Example ELE13: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, 10R, 11S, 12S, 16R) -10-allyl-11-hydroxy-8, 8,12 , 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14. 1.0] Heptadec-7-yloxycarbonyloxymethyl]- Phenoxy} -3,4,5-trihydroxy tetrahydro-pyran-2-carboxylic acid:
Analogous to Example ELE10, 320 mg (352 μmol) of the compound obtained according to Example ELE12 are reacted and, after processing and purification, 165 mg (190 μmol, 54%) of the title compound is isolated.
¹ H-NMR (d ₆ -DMSO): δ = 0.90 (3H), 0.98 (3H), 1.13 (3H), 1.23 (3H), 1.06- 1.58 (5H), 1.67 (1H), 2.02 (1H), 2.09-2. 31 (2H), 2.41-2. 78 (4H), 2.80 (3H), 2.90 (1H), 3.06-3. 40 (6H), 3.60 (1H), 4.66-4. 80 (3H) , 4.88-5. 03 (4H), 5.18 (1H), 5.27 (1H), 5.69 (1H), 5.99 (1H), 6.95 (2H), 7.15 (2H), 7.34 (1H), 7.37 (1H), 7.88 (1H), 8.02 (1H) ppm

Example ELE 14: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4-hydroxy-5, 5,9, 13-Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -phenoxy} -3, 4 , 5-Trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:

Example ELE14a: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4- (tert-butyl-dimethyl-silanyloxy) -5,5, 9, 13-Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -Phenoxy} -3,4,5-tris- (tert-butyl-dimethyl-silanyloxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE11a, 1.95 g (2.77 mmol) of the compound obtained according to Example ELE8b are reacted with the compound obtained according to Example EL5 and, after processing and purification, 2.79 g (2.06 mmol, 75 %) Of the title compound.

Example ELE14: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -phenoxy} -3, 4, 5-Trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE11, 2.78 g (2.06 mmol) of the compound obtained according to Example ELE14a are reacted and, after processing and purification, 1.00 g (1.12 mmol, 54%) of the title compound is isolated. To do.
¹ H-NMR (CDC1 ₃ ): δ = 1.00 (3H), 1.06 (3H), 1.13 (1H), 1.21 (3H), 1.48-1. 96 (5H), 1.70 (3H), 2.25-2. 54 (6H), 2.83 (3H), 2.87 (1H), 3.01 (1H), 3.10 (1H), 3.35 (1H), 3.46 (1H), 3.53 (1H), 3.74 (2H), 3.90 (1H), 3.98 (2H), 4.71 (2H), 4.86-5.00 (3H), 5.06- 5.23 (4H), 5.27 (1H), 5.35 (1H), 5.69 (1H), 5.82 (1H), 5.91 (1H), 7.05 (2H), 7.33 (3H), 7.79 (1H), 7.95 (1H) ppm.

Example ELE15: (2S, 3S, 4S, 5R, 6S) -6- {4- [(lS, 3S, 7S, 1 OR, ll S, 12S, 16R) -10-allyl-7-hydroxy-8, 8 , 12,16-Tetramethyl 3- (2-methyl-benzothiazol-5-yl) -5,9-dioxo-4,17-dioxa-bicyclo [14. 1. 0] heptadec-11-yloxycarbonyloxy Methyl] -phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2carboxylic acid allyl ester:
Analogously to Example ELE2, 1.30 g (1.45 mmol) of the compound obtained according to Example ELE14 are reacted and, after processing and purification, 1.15 g (1.26 mmol, 87%) of the title compound is isolated. To do.
¹ H-NMR (d ₆ -DMSO): δ = 0.92 (3H), 0.93 (3H), 1.17 (3H), 1.19 (3H), 1.23-1. 68 (7H), 2.04 (1H), 2.17 (1H ), 2.28 (2H), 2.38 (1H), 2.62 (1H), 2.80 (3H), 2.93 (1H), 3.25- 3.47 (3H), 3.60 (1H), 4.06 (1H), 4.10 (1H), 4.61 (2H), 4.87 (1H), 4.91 (1H), 4.99 (1H), 5.08 (2H), 5.11-5.22 (3H), 5.28 (1H), 5.32 (1H), 5.45 (1H), 5.51 ( 1H), 5.67 (1H), 5.88 (1H), 5.97 (1H), 7.03 (2H), 7.33 (2H), 7.47 (1H), 7.99 (2H) ppm.

Example ELE16: (2S, 3 S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, 1 OR, ll S, 12S, 16R) -10-allyl-7-hydroxy-8, 8,12,16-Tetramethyl 3- (2-methyl-benzothiazol-5-yl) -5,9-dioxo-4, 17-dioxa-bicyclo [14. 1.0] -heptadec-11-yloxycarbonyloxy Methyl] -phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2 carboxylic acid:
Analogously to Example ELE10, 354 mg (389 μmol) of the compound obtained according to Example ELE15 are reacted and, after processing and purification, 187 mg (215 μmol, 55%) of the title compound are isolated.
¹ H-NMR (d ₆ -DMSO): δ = 0.92 (3H), 0.93 (3H), 1.18 (3H), 1.20 (3H), 1.00-1.68 (5H), 2.04 (1H), 2.16 (1H ), 2.28 (2H), 2.38 (2H), 2.61 (1h), 2.80 (3H), 2.94 (1H), 3.07-3.40 (6H), 3.61 (1H), 4.07 (1H), 4.81 (1H) , 4.88 (1H), 4.91-5. 03 (3H), 5.09 (2H), 5.19 (1H), 5.21 (1H), 5.67 (1H), 5.96 (1H), 7.03 (2H), 7.32 (3H), 7.48 (1H), 7.99 (2H) ppm.

Example ELE17: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-chloro-phenoxy}- 3, 4, 5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:

Example ELE17a: (2S, 3 S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- (tert-butyl-dimethyl-silanyloxy ) -5,5, 9, 13-Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl ] -2-Chloro-phenoxy} -3,5-bistriisopropylsilanyloxy) -4-hydroxy-tetrahydro-pyran-2-carboxylic acid allyl ester:
In a mixture of 40 ml dimethylformamide and 16 ml trichloromethane, a solution of 1.41 g (2.00 mmol) of the compound obtained according to Example ELE1b was combined with 7.74 g of the compound obtained according to Example LE6, 1.0 g of chloride (I) And the suspension is stirred at 23 ° C. for 16 hours. It is then filtered, concentrated by evaporation and the residue is purified by chromatography on fine silica gel. 770 mg (568 μmol, 28%) of the title compound is isolated.

Example ELE17: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-chloro-phenoxy}- 3, 4,5-Trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE11, 1.54 g (1.14 mmol) of the compound obtained according to Example ELE17a are reacted and, after processing and purification, 612 mg (659 μmol, 58%) of the title compound is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.02 (3H), 1.14 (3H), 1.16 (3H), 1.70 (3H), 1.20-1.90 (5H), 2.18-2.59 (6H), 2.69 (1H), 2.77 (3H), 2.92 (1H), 3.14 (1H), 3.32 (1H), 3.37-3. 53 (3H), 3.64-4. 02 (5H), 4.54 (1H), 4.66-4 75 (3H), 4.86 (1H), 5.01 (1H), 5.06 (1H), 5.16 (1H), 5.28 (1H), 5.37 (1H), 5.56 (1H), 5.72 (1H), 5.90 (1H) , 5.96 (1H), 6.88 (1H), 7.03 (1H), 7.08 (1H), 7.33 (1H), 7.74 (1H), 7.91 (1H) ppm.

Example ELE 18: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, lOR, 1 lS, 12S, 16R) -10-allyl-l l-hydroxy-8, 8,12, 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4,17-dioxa-bicyclo [14.1. 0] -heptadec-7-yloxycarbonyl Oxymethyl] -2-chloro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE2, 610 mg (657 μmol) of the compound obtained according to Example ELE17 are reacted and, after processing and purification, 517 g (547 μmol, 83%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.03 (3H), 1.12 (3H), 1.18 (3H), 1.32 (3H), 1.07-1. 83 (8H), 2.01-2. 17 (2H), 2.29 -2. 59 (4H), 2.72 (1H), 2.80 (3H), 2.83 (1H), 3.45 (1H), 3.71 (2H), 3.81 (1H), 3.93 (1H), 3.95 (1H), 4.56 ( 1H), 4.63-4.75 (3H), 4.80 (1H), 5.02 (1H), 5.06 (1H), 5.27 (1H), 5.36 (1H), 5.46 (1H), 5.71 (1H), 5.92 (1H ), 6.03 (1H), 6.94 (1H), 7.05 (1H), 7.10 (1H), 7.28 (1H), 7.76 (1H), 7.88 (1H) ppm.

Example ELE 19: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, 10R, 11S, 12S, 16R) -10-allyl-11-hydroxy-8, 8, 12, 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4,17-dioxa-bicyclo [14.1. 0] -heptadec-7-yloxycarbonyloxymethyl ] -2-Chloro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid:
Analogous to Example ELE10, 310 mg (328 μmol) of the compound obtained according to Example ELE18 are reacted and, after processing and purification, 160 mg (177 μmol, 54%) of the title compound are isolated.
¹ H-NMR (d ₆ -DMSO): δ = 0.92 (3H), 0.98 (3H), 1.14 (3H), 1.22 (3H), 1.07- 1.72 (7H), 2.02 (1H), 2.12-2. 50 (4H), 2.55 (1H), 2.66 (1H), 2.73 (1H), 2.78 (3H), 2.92 (1H), 3.12 (1H), 3.24 (1H), 3.31 (3H), 3.38 (1H), 3.59 (1H), 4.70 (1H), 4.76 (1H), 4.88- 5.02 (4H), 5.18 (1H), 5.28 (1H), 5.70 (1H), 6.00 (1H), 7.15 (2H), 7.25 (1H) , 7.37 (1H), 7.88 (1H), 8.02 (1H).

Example ELE20: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -2-chloro-phenoxy}- 3, 4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:

Example ELE20a: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4- (tert-butyl-dimethyl-silanyloxy) -5,5, 9, 13-Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -2-chloro-phenoxy} -4-hydroxy-3,5 bis-triisopropylsilanyloxy-tetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE17a, 2.13 g (3.02 mmol) of the compound obtained according to Example ELE8b are reacted with the compound obtained according to Example ELE6 and, after processing and purification, 1.71 g (1.26 mmol, 42 mol). %) Of the title compound is isolated.

Example ELE20: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-4-hydroxy-5, 5, 9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-8-yloxycarbonyloxymethyl] -2-chloro-phenoxy}- 3, 4,5-Trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE11, 930 mg (686 μmol) of the compound obtained according to Example ELE20a are reacted and, after processing and purification, 460 mg (495 μmol, 72%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.02 (3H), 1.06 (3H), 1.14 (1H), 1.22 (3H), 1.51-1. 95 (6H), 1.70 (3H), 2.28-2. 43 (3H), 2.50 (2H), 2.84 (3H), 2.88 (1H), 2.98 (1H), 3.10 (1H), 3.23 (1H), 3.39 (1H), 3.53 (1H), 3.73 (1H), 3.82 (1H), 3.88-4. 04 (3H), 4.72 (2H), 4.85 (1H), 4.92 (1H), 4.98 (1H), 5.10 (2H), 5.15 (1H), 5.21 (1H), 5.28 ( 1H), 5.36 (1H), 5.70 (1H), 5.82 (1H), 5.93 (1H), 7.20-7. 28 (2H), 7.33 (1H), 7.44 (1H), 7.79 (1H), 7.95 (1H ) ppm.

Example ELE21: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, 10R, 11S, 12S, 16R) -10-allyl-7-hydroxy-8, 8,12 , 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14. 1. 0] -heptadec-11-yloxycarbonyloxy Methyl] -2-chloro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE2, 610 mg (657 μmol) of the compound obtained according to Example ELE20 are reacted and, after processing and purification, 601 mg (636 μmol, 97%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 0.96 (3H), 1.03 (3H), 1.07-1.82 (8H), 1.23 (3H), 1.31 (3H), 2.15 (2H), 2.34 (2H), 2.52 (1H), 2.61 (1H), 2.71 (1H), 2.84 (3H), 3.04 (1H), 3.21 (1H), 3.45 (1H), 3.66-4. 15 (6H), 4.30 0 (1H ), 4.71 (2H), 4.85 (1H), 4.91 (1H), 4.96 (1H), 5.08 (1H), 5.21 (1H), 5.28 (1H), 5.35 (1H), 5.72 (1H), 5.92 (1H ), 6.24 (1H), 7.23 (2H), 7.36 (1H), 7.42 (1H), 7.83 (1H), 8.00 (1H) ppm

Example ELE22: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, 1 OR, ll S, 12S, 16R) -10-allyl-7-hydroxy-8, 8 , 12,16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5,9-dioxo-4, 17-dioxa-bicyclo [14.1. 0] -heptadec-11-yloxycarbonyloxy Methyl] -2-chloro-phenoxy} -3,4,5-trihydroxy-tetrahydro-pyran-2-carboxylic acid:
Analogously to Example ELE10, 302 mg (320 μmol) of the compound obtained according to Example ELE21 are reacted and, after processing and purification, 178 mg (197 μmol, 62%) of the title compound are isolated.
¹ H-NMR (d ₆ -DMSO): δ = 0.93 (6H), 1.06-1.70 (6H), 1.18 (3H), 1.20 (3H), 2.05 (1H), 2.17 (1H), 2.21-2 47 (4H), 2.61 (1H), 2.80 (3H), 2.93 (1H), 3.11 (1H), 3.26 (2H), 3.32 (1H), 3.42 (1H), 3.62 (1H), 4.08 (1H) , 4.85-5. 04 (5H), 5.09 (2H), 5.20 (2H), 5.67 (1H), 5.96 (1H), 7.19-7.36 (3H), 7.45 (1H), 7.48 (1H), 7.99 (2H) ppm.

Example ELE23: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-methoxy-phenoxy}- 3, 4,5-Trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:

Example ELE23a: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- (tert-butyl-dimethyl-silanyloxy) -5,5, 9, 13-Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-methoxy-phenoxy} -3,4,5-tris- (tert-butyl-dimethyl-silanyloxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE1c, 1.15 g (1.63 mmol) of the compound obtained according to Example ELE1b are reacted with the compound obtained according to Example EL7 and, after processing and purification, 1.44 g (1.04 mmol, 64 %) Of the title compound.

Example ELE23: (2S, 3 S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-methoxy-phenoxy} -3, 4, 5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE11, 1.44 g (1.04 mmol) of the compound obtained according to Example ELE23a are reacted and, after processing and purification, 386 mg (418 μmol, 40%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.01 (3H), 1.13 (3H), 1.15 (3H), 1.31-1. 90 (5H), 1.70 (3H), 2.25 (1H), 2.30-2.55 (4H), 2.58 (1H), 2.68 (1H), 2.74 (3H), 2.94 (1H), 3.40 (1H), 3.46-3. 97 (8H), 3.79 (3H), 4.04 (1H), 4.56 ( 1H), 4.68-4. 78 (4H), 5.00 (1H), 5.04 (1H), 5.16 (1H), 5.27 (1H), 5.35 (1H), 5.55 (1H), 5.71 (1H), 5.92 (2H ), 6.57 (1H), 6.60 (1H), 7.06 (1H), 7.34 (1H), 7.73 (1H), 7.92 (1H) ppm.

Example ELE24: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, 10R, 11S, 12S, 16R) -10-allyl-11-hydroxy-8, 8,12 , 16-Tetramethyl 3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14.1. 0] -heptadec-7-yloxycarbonyloxymethyl]- 2-methoxy-phenoxy} -3,4,5-trihydroxy-tetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE2, 384 mg (416 μmol) of the compound obtained according to Example ELE23 are reacted and, after processing and purification, 287 mg (296 μmol, 71%) of the title compound are isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.04 (3H), 1.11 (3H), 1.18 (3H), 1.32 (3H), 1.20-2.59 (13H), 2.70 (1H), 2.79 (4H), 3.17 (1H), 3.32 (1H), 3.44 (1H), 3.58-3. 92 (6H), 3.82 (3H), 4.55-4. 80 (5H), 5.01 (1H), 5.05 (1H), 5.28 ( 1H), 5.37 (1H), 5.44 (1H), 5.72 (1H), 5.91 (1H), 5.99 (1H), 6.69 (2H), 7.02 (1H), 7.26 (1H), 7.76 (1H), 7.87 ( 1H) ppm.

Example ELE25: (2S, 3S, 4S, 5R, 6S) -6- {4- [(lS, 3S, 7S, lOR, 1 lS, 12S, 16R) -10-allyl-l l-hydroxy-8, 8 , 12,16-Tetramethyl 3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14.1. 0] -heptadec-7-yloxycarbonyloxymethyl ] -2-Methoxy-phenoxy} -3,4,5-trihydroxy tetrahydro-pyran-2-carboxylic acid:
Analogously to Example ELE10, 100 mg (106 μmol) of the compound obtained according to Example ELE24 are reacted and, after processing and purification, 64 mg (71 μmol, 67%) of the title compound are isolated.
¹ H-NMR (d ₆ -DMSO): δ = 0.91 (3H), 0.98 (3H), 1.15 (3H), 1.23 (3H), 1.07- 2.76 (11H), 2.79 (3H), 2.90 (1H), 3.05-3. 42 (8H), 3.59 (1H), 3.72 (3H), 4.66-5. 01 (7H), 5.09 (1H), 5.27 (1H), 5.71 (1H), 5.98 (1H), 6.75 ( 1H), 6.85 (1H), 7.00 (1H), 7.36 (2H), 7.88 (1H), 8.02 (1H) ppm.

Example ELE26: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-fluoro-phenoxy}- 3, 4, 5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:

Example ELE26a: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8- (tert-butyl-dimethyl-silanyloxy -5,5, 9, 13-Tetramethyl 16- (2-methyl-benzothiazol-5-yl) -2,6-dioxooxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-methoxy-phenoxy} -3,4,5-tris- (tert-butyl-dimethyl-silanyloxy) -tetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE1c, 2.0 g (2.84 mmol) of the compound obtained according to Example ELE1b are reacted with the compound obtained according to Example EL8 and, after processing and purification, 2.06 g (1.50 mmol, 53 %) Of the title compound.

Example ELE26: (2S, 3S, 4S, 5R, 6S) -6- {4- [(4S, 7R, 8S, 9S, 13Z, 16S) -7-allyl-8-hydroxy-5, 5,9, 13 -Tetramethyl-16- (2-methyl-benzothiazol-5-yl) -2,6-dioxo-oxacyclohexadec-13-en-4-yloxycarbonyloxymethyl] -2-fluoro-phenoxy}- 3, 4,5-trihydroxytetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE11, 2.06 g (1.50 mmol) of the compound obtained according to Example ELE26a are reacted and, after processing and purification, 1.01 g (1.11 mmol, 74%) of the title compound is isolated. To do.
¹ H-NMR (CDC1 ₃ ): δ = 1.02 (3H), 1.14 (6H), 1.20-2. 61 (11H), 1.70 (3H), 2.68 (1H), 2.78 (3H), 2.91 (1H), 3.18-4. 01 (10H), 4.56 (1H), 4.65-4.76 (3H), 4.90 (1H), 5.01 (1H), 5.06 (1H), 5.16 (1H), 5.27 (1H), 5.34 ( 1H), 5.55 (1H), 5.72 (1H), 5.89 (1H), 5.93 (1H), 6.73 (2H), 7.05 (1H), 7.33 (1H), 7.73 (1H), 7.88 (1H) ppm.

Example ELE27: (2S, 3S, 4S, 5R, 6S) -6- {4-[(1S, 3S, 7S, 10R, 11S, 12S, 16R) -10-allyl-11-hydroxy-8, 8,12 , 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4,17-dioxa-bicyclo [14. 1.0] -heptadec-7-yloxycarbonyloxymethyl] -2-Fluoro-phenoxy} -3,4,5-trihydroxy-tetrahydro-pyran-2-carboxylic acid allyl ester:
Analogously to Example ELE2, 1.01 g (1.11 mmol) of the compound obtained according to Example ELE26 is reacted and, after processing and purification, 657 mg (708 μmol, 64%) of the title compound is isolated.
¹ H-NMR (CDC1 ₃ ): δ = 1.04 (3H), 1.13 (3H), 1.32 (3H), 1.31 (3H), 1.24-1.84 (7H), 1.98-2.17 (2H), 2.29 -2. 59 (4H), 2.71 (1H), 2.80 (3H), 2.82 (1H), 3.29 (1H), 3.38 (1H), 3.45 (1H), 3.64-3. 96 (6H), 4.59 (1H), 4.65-4. 73 (3H), 4.83 (1H), 5.01 (1H), 5.06 (1H), 5.26 (1H), 5.34 (1H), 5.46 (1H), 5.71 (1H), 5.91 ( 1H), 6.01 (1H), 6.81 (2H), 7.04 (1H), 7.28 (1H), 7.75 (1H), 7.86 (1H) ppm.

Example ELE28: (2S, 3S, 4S, 5R, 6S) -6- {4-[(lS, 3S, 7S, lOR, llS, 12S, 16R) -10-allyl-l l-hydroxy-8, 8, 12, 16-Tetramethyl-3- (2-methyl-benzothiazol-5-yl) -5, 9-dioxo-4, 17-dioxa-bicyclo [14. 1.0] -heptadec-7-yloxycarbonyloxymethyl ] -2-Fluoro-phenoxy} -3,4,5-trihydroxytetrahydro-pyran-2-carboxylic acid:
Analogously to Example ELE10, 350 mg (377 μmol) of the compound obtained according to Example ELE27 are reacted and, after processing and purification, 234 mg (264 μmol, 70%) of the title compound are isolated.
¹ H-NMR (d ₆ -DMSO): δ = 0.92 (3H), 0.98 (3H), 1.14 (3H), 1.23 (3H), 1.08- 1.60 (7H), 1.66 (1H), 2.02 (1H), 2.11-2. 75 (5H), 2.78 (3H), 2.91 (1H), 3.01-3. 41 (5H), 3.60 (1H), 4.69 (1H), 4.77 (1H), 4.86 (1H), 4.89- 5. 02 (4H), 5.25 (1H), 5.28 (1H), 5.71 (1H), 5.99 (1H), 6.99 (1H), 7.06 (1H), 7.19 (1H), 7.26 (1H), 7.37 (1H ), 7.87 (1H), 8.02 (1H) ppm.

Claims (22)

The following general formula:

[Wherein R ^1a , R ^1b are independently of each other hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, or together, a — (CH ₂ ) _m group (where m is 2-5 Is);
R ^2a and R ^2b, independently of one another, are hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, or taken together — (CH ₂ ) _n group (where n is 2 to 5), or C ₂ -C ₁₀ alkenyl or C ₂ -C ₁₀ alkynyl;
R ³ is hydrogen, C ₁ -C ₁₀ alkyl, aryl or aralkyl;
R ^4a and R ^4b are each independently hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, or together — (CH ₂ ) _p group, where p is 2-5. ;
R ⁵ is hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, C 0 ₂ H, C 0 ₂ alkyl, CH ₂ OH, CH ₂ 0 alkyl, CH ₂ 0 acyl, CN, CH ₂ NH ₂ , CH ₂ N ( Alkyl, acyl) _1,2 , or CH ₂ Hal;
Hal is a halogen atom;
R ⁶ and R ⁷ are in each case hydrogen, or an additional bond together, or an oxygen atom together, an NH group together, or an N-alkyl group together, or together. And CH ₂ group;
G is an oxygen atom or CH ₂ ;
DE is a group H ₂ C—CH ₂ , HC═CH, C≡C, CH (OH) —CH (OH), CH (OH) —CH ₂ , CH ₂ —CH (OH), the following groups:

O—CH ₂ or, when G represents a CH ₂ group, CH ₂ —O;
W is a group C (= X) R ⁸ , or a bi- or tricyclic aromatic or heteroaromatic group;
L ³ is hydrogen or, when the group in W contains a hydroxyl group, forms the group OL ⁴ with the latter, or when the group in W contains an amino group, the group NR ²⁵ -L ⁴ together with the latter Forming;
R ²⁵ is hydrogen or C ₁ -C ₁₀ alkyl;
X is an oxygen atom, or two OR ²⁰ groups, or a C ₂ -C ₁₀ alkylenedioxy group (should be linear or branched), or H / OR ⁹ , or a CR ¹⁰ R ¹¹ group ;
R ⁸ is hydrogen, C ₁ -C ₁₀ alkyl, aryl, aralkyl, halogen or CN;
R ⁹ is hydrogen or a protecting group PG ^X ;
R ¹⁰ and R ^11, in each case, independently of one another, are hydrogen, C ₁ -C ₂₀ alkyl, aryl or aralkyl, or together with a methylene carbon atom, form a 5- to 7-membered carbocyclic ring. Forming;
Z may represent oxygen or H / OR ¹² ;
R ¹² can represent hydrogen or the protecting group PG ^Z
Alpha-Y is a group OC (= O), O- CH 2, CH 2 -C (= O), NR 21 -C (= O) or NR ²¹ may represent -SO _2;
R ²⁰ can represent C ₁ -C ₂₀ alkyl;
R ²¹ may represent a hydrogen atom or C ₁ -C ₁₀ alkyl;
PG ^X , PG ^Y and PG ^Z may represent the protecting group PG;
L ¹ , L ² , and L ⁴ each independently represent hydrogen, a group C (= O) Cl, a group C (= S) Cl, a group PG ^Y , or a linker recognition unit of the general formula (III) Wherein at least one substituent L ¹ , L ² or L ⁴ represents a linker recognition unit of general formula (III); said linker recognition unit of general formula (III) has the following structure:

Where
R ^22a and R ^22b each independently represent hydrogen, C ₁ -C ₂₀ alkyl, C ₁ -C ₂₀ acyl, C ₁ -C ₂₀ acyloxy, aryl, aralkyl, hydroxy, alkoxy, CO ₂ H, CO ₂ alkyl, Can represent halogen, CN, NO ₂ , NH ₂ or N ₃ ;
U ^{is, -C (= O) NR 23} -, -C (= S) NR 23 -, -C (= O) NR 23 -CH 2 -, -C (= S) NR 23 -CH 2 -, - C (= O) O-, -C (= S) O-, -C (= O) O-CH _2- , -C (= S) O-CH ₂ -can be represented;
R ²³ may represent hydrogen or C ₁ -C ₁₀ alkyl; and
EG represents the following general formula (IV):

Is a recognition unit represented by
R ²⁴ may represent the group CH ₂ 0PG ⁴ or the group CO ₂ R ²⁶ ;
PG ¹ , PG ² , PG ³ and PG ⁴ can independently represent hydrogen or the protecting group PG;
R ²⁶ is hydrogen, C ₁ -C ₂₀ alkyl, C ₁ -C ₂₀ alkenyl, C ₄ -C ₇ cycloalkyl (can contain an oxygen atom), aryl, aralkyl, tris (C ₁ -C ₂₀ alkyl) Silyl, bis (C ₁ -C ₂₀ alkyl) -arylsilyl, (C ₁ -C ₂₀ alkyl) -diarylsilyl, or tris (aralkyl) -silyl]
Conjugates as homogeneous isomers or mixtures of different isomers and / or as pharmaceutically acceptable salts thereof. AY represents OC (= O) or NR ²¹ -C (= O);
DE represents a H ₂ C—CH ₂ group or a HC═CH group;
G represents a CH ₂ group;
Z represents an oxygen atom;
When R ^1a , R ^1b are individual, C ₁ -C ₁₀ alkyl, or together, represents a — (CH ₂ ) _p group (p is 2, 3 or 4);
R ^2a and R ^2b each independently represent hydrogen, C ₁ -C ₁₀ alkyl, C ₂ -C ₁₀ alkenyl, or C ₂ -C ₁₀ alkynyl;
R ³ represents hydrogen;
R ^4a and R ^4b each independently represent hydrogen or C ₁ -C ₁₀ alkyl;
R ⁵ represents hydrogen, C ₁ -C ₄ alkyl, CH ₂ OH, CH ₂ NH ₂ , CH ₂ N (alkyl, acyl) _1,2 or CH ₂ Hal;
R ⁶ and R ⁷ together represent an additional bond, together NH group, or N-alkyl group together, or CH ₂ group together, or oxygen atom together. ;
W is a group C (= X) R ⁸ , or 2-methylbenzothiazol-5-yl group, or 2-methylbenzoxazol-5-yl group, or quinolin-7-yl group, or 2-aminomethyl Represents a benzothiazol-5-yl group, or a 2-hydroxymethylbenzothiazol-5-yl group, or a 2-aminomethylbenzoxazol-5-yl group, or a 2-hydroxymethylbenzoxazol-5-yl group; ;
X represents a CR ¹⁰ R ¹¹ group;
R ⁸ represents hydrogen, C ₁ -C ₄ alkyl, a fluorine atom, a chlorine atom, or a bromine atom;
R ¹⁰ / R ¹¹ is hydrogen / 2-methylthiazol-4-yl, or hydrogen / 2-pyridyl, or hydrogen / 2-methyloxazol-4-yl, or hydrogen / 2-aminomethylthiazol-4-yl, Or a conjugate according to claim 1, which represents hydrogen / 2-aminomethyloxazol-4-yl, hydrogen / 2-hydroxymethylthiazol-4-yl, or hydrogen / 2-hydroxymethyloxazol-4-yl. R ^22a and R ^22b represent C ₁ -C ₈ -alkyl, C ₁ -C ₈ -alkoxy, halogen, nitro, CN, N ₃ , NH ₂ , or CO _2- (C ₁ -C ₈ -alkyl) The joined body according to claim 1 or 2. The joined body according to claim 1, wherein R ²⁶ represents C ₁ -C ₈ -alkyl or C ₂ -C ₈ -alkenyl. R ^2a represents hydrogen and R ^2b represents C ₁ -C ₇ -alkyl, C ₂ -C ₇ -alkenyl or C ₂ -C ₇ -alkynyl; or R ^2b represents hydrogen and R ^2a represents C The joined body according to any one of claims 1 to 4, which represents ₁ -C ₇ -alkyl, C ₂ -C ₇ -alkenyl, or C ₂ -C ₇ -alkynyl. R ^22a , R ^22b is methyl, ethyl, propyl, i-propyl, tert-butyl, CF ₃ , C ₂ F ₅ , F, Cl, nitro, CN, N ₃ , NH ₂ , CO ₂ -methyl, CO ₂ - ethyl, CO ₂ - propyl or CO _{2-i-conjugate} according to any one of claims 1 to 5 representing the propyl. The joined body according to any one of claims 1 to 6, wherein R ²⁶ represents methyl, ethyl, propyl, i-propyl, t-butyl, CF ₃ , propenyl, or butenyl. R ^2a represents hydrogen and R ^2b represents methyl, ethyl, propyl, i-propyl, propenyl, butenyl, propynyl or butynyl; or R ^2b represents hydrogen and R ^2a represents methyl, ethyl, propyl, i The conjugate according to any one of claims 1 to 7, which represents -propyl, propenyl, butenyl, propynyl or butynyl. The effector element is:
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-methyl-2- (2-methyl-thiazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-methyl-vinyl] -5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-methyl-vinyl]-4,8-dihydroxy-5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-methyl-2- (2 -Methyl-thiazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-methyl-vinyl ] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(1 S, 3 S (E), 7S, 10R, 11S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-methyl-vinyl] -7, 11- Dihydroxy-8, 8,10, 12, 16-pentamethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-7-ethyl-5, 5,9, 13-tetramethyl-16- [1-methyl-2- (2- Methyl-thiazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-methyl-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-methyl-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (E), 7S, 1OR, ll S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [l-methyl-2 -(2-Methyl-thiazol-4-yl) -vinyl] -4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-methyl-vinyl] -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3 S (E), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-methyl-vinyl] -7, 11 -Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-fluoro-2- (2-methyl-thiazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-fluoro-vinyl] -5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-fluoro-vinyl] -4,8-dihydroxy-5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-fluoro-2- (2 -Methyl-thiazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-fluoro- Vinyl] -8, 8,10, 12, 16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 1OR, ll S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-fluoro-vinyl] -7, 11- Dihydroxy-8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5, 5,7, 9, 13-pentamethyl-16- [1-chloro-2- (2-methyl-thiazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-chloro-vinyl] -5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-chloro-vinyl] -4,8-dihydroxy-5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (Z), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-chloro-2- ( 2-Methyl-thiazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-chloro- Vinyl] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-chloro-vinyl] -7, 11 -Dihydroxy-8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-fluoro-2- (2- Methyl-thiazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -l-fluoro-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-fluoro-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [l-fluoro-2- ( 2-methyl-thiazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-fluoro-vinyl ] -10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-fluoro-vinyl] -7, 11 -Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-chloro-2- (2- Methyl-thiazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -1-chloro-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-thiazol-4-yl) -1-chloro-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-chloro-2 -(2-Methyl-thiazol-4-yl) -vinyl] -4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -1-chloro-vinyl ] -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 1OR, ll S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -1-chloro-vinyl] -7, 11- Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-methyl-2- (2-pyridyl)- Vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-methyl-2- (2-pyridyl ) -Vinyl] -4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-methyl-2- (2- Pyridyl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-methyl-2- (2-pyridyl) -vinyl] -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-fluoro-2- (2-pyridyl)- Vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-fluoro-2- (2- Pyridyl) -vinyl] -4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-chloro-2- (2-pyridyl)- Vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-chloro-2- (2-pyridyl ) -Vinyl] -4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-fluoro-2- (2- Pyridyl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-fluoro-2- ( 2-pyridyl) -vinyl] -4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-chloro-2- (2- Pyridyl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-chloro-2- (2-pyridyl) -vinyl] -4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-methyl-2- (2-methyl-oxazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-methyl-vinyl] -5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-methyl-vinyl]-4,8-dihydroxy-5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (E), 7S, 10R, 11 S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-methyl-2- ( 2-Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-methyl-vinyl]- 8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, ll S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-methyl-vinyl] -7, 11- Dihydroxy-8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-methyl-2- (2- Methyl-oxazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-methyl-vinyl] -7- Ethyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-methyl-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-methyl-2 -(2-Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, ll S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-methyl-vinyl ] -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1S, 3S (E), 7S, 10R, 11S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-methyl-vinyl] -7, 11-dihydroxy- 10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-fluoro-2- (2-methyl-oxazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-fluoro-vinyl] -5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-fluoro-vinyl] -4,8-dihydroxy-5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-fluoro-2- (2 -Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -7,11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-fluoro-vinyl ] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3 S (Z), 7S, 10R, 11S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-fluoro-vinyl] -7, 11- Dihydroxy-8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [1-chloro-2- (2-methyl-oxazole -4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-4, 8-dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-chloro-vinyl] -5, 5, 7,9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-chloro-vinyl] -4,8-dihydroxy-5, 5,7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [1-chloro-2- (2- Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecane-5, 9-dione;
(1 S, 3 S (Z), 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-chloro- Vinyl] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(lS, 3S (Z), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-chloro-vinyl] -7, 11-dihydroxy -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-fluoro-2- (2- Methyl-oxazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-fluoro-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-fluoro-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [l-fluoro-2- (2-Methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-fluoro-vinyl] -10-ethyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-fluoro-vinyl] -7, 11-dihydroxy -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [1-chloro-2- (2- Methyl-oxazol-4-yl) -vinyl] -oxacyclohexadec-13-en-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-oxazol-4-yl) -1-chloro-vinyl] -7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (Z))-16- [2- (2-Aminomethyl-oxazol-4-yl) -1-chloro-vinyl]-4,8-dihydroxy-7- Ethyl-5,5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [1-chloro-2- ( 2-methyl-oxazol-4-yl) -vinyl] -4, 17-dioxa-bicyclo [14.1.0] heptadecan-5,9-dione;
(1 S, 3S (Z), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- [2- (2-hydroxymethyl-oxazol-4-yl) -1-chloro-vinyl] -10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3S (Z), 7S, 1OR, ll S, 12S, 16R) -3- [2- (2-Aminomethyl-oxazol-4-yl) -1-chloro-vinyl] -7, 11- Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- [2- (2-methyl-thiazol-4-yl ) -Vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -vinyl] -5, 5,7, 9,13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-thiazol-4-yl) -vinyl] -4, 8-dihydroxy-5,5, 7, 9, 13-pentamethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [2- (2-methyl-thiazole-4 -Yl) -vinyl] -4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -vinyl] -8, 8,10, 12,16-pentamethyl-4, 17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3 S (E), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -vinyl] -7, 11-dihydroxy-8 , 8,10,12,16-pentamethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- [2- (2-methyl-thiazole- 4-yl) -vinyl] -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-dihydroxy-16- [2- (2-hydroxymethyl-thiazol-4-yl) -vinyl] -7-ethyl-5, 5,9,13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-16- [2- (2-Aminomethyl-thiazol-4-yl) -vinyl] -4, 8-dihydroxy-7-ethyl-5, 5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [2- (2-methyl -Thiazol-4-yl) -vinyl] -4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 10R, 11S, 12S, 16R) -7,11-Dihydroxy-3- [2- (2-hydroxymethyl-thiazol-4-yl) -vinyl] -10-ethyl -8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -3- [2- (2-Aminomethyl-thiazol-4-yl) -vinyl] -7, 11-dihydroxy-10- Ethyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E)) -4, 8-Dihydroxy-5,5, 7,9, 13-pentamethyl-16- [2- (2-pyridyl) -vinyl] -oxa Cyclohexadec-13-ene-2,6-dione;
(1S, 3S, (E), 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12,16-pentamethyl-3- [2- (2-pyridyl) -vinyl ] -4, 17-Dioxa-bicyclo [14. 1.0] Heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S (E))-4, 8-Dihydroxy-7-ethyl-5, 5,9, 13-tetramethyl-16- [2- (2-pyridyl) -vinyl ] -Oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S (E), 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- [2- (2-pyridyl ) -Vinyl] -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- (2-methyl-benzothiazol-5-yl) -oxacyclohexa Dec-13-ene-2, 6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -5,5, 7,9, 13-pentamethyl-oxacyclohex Sadec-13-ene-2, 6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-oxacyclohex Sadec-13-ene-2, 6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12, 16-pentamethyl-3- (2-methyl-benzothiazol-5-yl) -4 , 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -8,8, 10,12, 16- Pentamethyl-4,17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-8,8, 10,12, 16-pentamethyl -4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-ethyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-ethyl-5,5, 9,13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazol-5-yl ) -4,17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(lS, 3S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-ethyl-8, 8, 12, 16 -Tetramethyl-4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-10-ethyl-8, 8,12, 16- Tetramethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-propyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-propyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-propyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 125, 16R) -7, 11-Dihydroxy-10-propyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole- 5-yl) -4,17-dioxa-bicyclo [14.1.0] heptadecan-5,9-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7,11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-propyl-8, 8,12, 16- Tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7, 11-dihydroxy-10-propyl-8, 8,12 , 16-tetramethyl-4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-butyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-butyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-butyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7,11-Dihydroxy-10-butyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazol-5-yl ) -4,17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-butyl-8, 8,12, 16 -Tetramethyl-4,17-dioxa-bicyclo [14. 1.0] -heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7, 11-dihydroxy-10-butyl-8, 8,12 , 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-Dihydroxy-7-allyl-5, 5,9,13-tetramethyl-16- (2-methyl-benzothiazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8 S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-allyl-5,5, 9, 13-tetra Methyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-allyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-10-allyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole- 5-yl) -4,17-dioxa-bicyclo [14.1. 0] heptadecane-5, 9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-allyl-8, 8, 12, 16 -Tetramethyl-4, 17-dioxa-bicyclo [14.1. 0] -heptadecane-5,9-dione;
(1 S, 3 S, 7S, 10R, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-10-allyl-8, 8,12 , 16-Tetramethyl-4,17-dioxa-bicyclo [14.1. 0] Heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-prop-2-ynyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-prop-2-ynyl-5, 5,9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-prop-2-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-prop-2-ynyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole -5-yl) -4,17-dioxa-bicyclo (14.1.0) heptadecane-5,9-dione;
(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-prop-2-ynyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-10-prop-2-ynyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1. 0] -heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-but-3-enyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4,8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-but-3-enyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-but-3-enyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-but-3-enyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole -5-yl) -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-but-3-enyl-8 , 8, 12, 16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] -heptadecane-5,9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7,11-dihydroxy-10-but-3-enyl-8, 8 , 12,16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-but-3-ynyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzothiazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzothiazol-5-yl) -7-but-3-ynyl-5, 5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzothiazol-5-yl) -4, 8-dihydroxy-7-but-3-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-but-3-ynyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzothiazole -5-yl) -4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, ll S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzothiazol-5-yl) -10-but-3-ynyl-8 , 8,12, 16-Tetramethyl-4,17-dioxa-bicyclo [14. 1.0] -heptadecane-5,9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzothiazol-5-yl) -7, 11-dihydroxy-10-but-3-ynyl-8, 8 , 12,16-tetramethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-16- (2-methyl-benzoxazol-5-yl) -oxacyclohexa Dec-13-ene-2, 6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl)-5,5, 7,9, 13-pentamethyl-oxacyclohex Sadec-13-ene-2, 6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-5,5, 7,9, 13-pentamethyl-oxacyclohex Sadec-13-ene-2, 6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-dihydroxy-8, 8,10, 12, 16-pentamethyl-3- (2-methyl-benzoxazol-5-yl) -4 , 17-Dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, ll S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -8,8, 10,12, 16 -Pentamethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-8,8, 10,12, 16- Pentamethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-ethyl-5,5, 9,13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-ethyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-ethyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazol-5-yl ) -4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 10R, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-ethyl-8, 8,12 , 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5,9-dione;
(1S, 3S, 7S, 1OR, ll S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-10-ethyl-8, 8,12, 16 -Tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-propyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-propyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-propyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-propyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazole-5 -Yl) -4,17-dioxa-bicyclo [14.1. 0] heptadecan-5,9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-propyl-8, 8,12 , 16-Tetramethyl-4,17-dioxa-bicyclo [14.1. 0] Heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 10R, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7,11-dihydroxy-10-propyl-8, 8,12 , 16-tetramethyl-4,17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-butyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-butyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-butyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(1S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-butyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazol-5-yl ) -4,17-dioxa-bicyclo [14.1. 0] heptadecane-5,9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-butyl-8, 8,12 , 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(1 S, 3S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7,11-dihydroxy-10-butyl-8, 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-allyl-5, 5,9, 13-tetramethyl-16- (2-methyl-benzoxazol-5-yl)- Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-allyl-5,5, 9,13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-allyl-5,5, 9, 13-tetramethyl -Oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-allyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazol-5-yl ) -4, 17-dioxa-bicyclo [14.1. 0] heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-allyl-8, 8,12 , 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5, 9-dione;
(1 S, 3S, 7S, 10R, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-10-allyl-8, 8,12, 16-tetramethyl-4, 17-dioxa-bicyclo [14. 1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-prop-2-ynyl-5,5, 9,13-tetramethyl-16- (2-methyl-benzoxazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-prop-2-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8 S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-prop-2-ynyl-5, 5,9 , 13-Tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-prop-2-ynyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benz Oxazol-5-yl) -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-prop-2-ynyl-8 , 8,12, 16-Tetramethyl-4,17-dioxa-bicyclo [14. 1.0] Heptadecane-5, 9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-10-prop-2-ynyl-8, 8 , 12,16-Tetramethyl-4,17-dioxa-bicyclo [14. 1. 0] -heptadecane-5, 9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-but-3-enyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-but-3-enyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-but-3-enyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(1 S, 3 S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-but-3-enyl-8, 8,12, 16-tetramethyl-3- (2-methyl- Benzoxazol-5-yl) -4, 17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-but-3-enyl-8, 8 , 12,16-Tetramethyl-4,17-dioxa-bicyclo [14. 1. 0] heptadecane-5, 9-dione;
(1 S, 3 S, 7S, 10R, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7,11-dihydroxy-10-but-3-enyl-8 , 8,12,16-Tetramethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-7-but-3-ynyl-5,5, 9, 13-tetramethyl-16- (2-methyl-benzoxazole-5 -Yl) -oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -4, 8-Dihydroxy-16- (2-hydroxymethyl-benzoxazol-5-yl) -7-but-3-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(4S, 7R, 8S, 9S, 13Z, 16S) -16- (2-Aminomethyl-benzoxazol-5-yl) -4, 8-dihydroxy-7-but-3-ynyl-5,5, 9, 13-tetramethyl-oxacyclohexadec-13-ene-2,6-dione;
(lS, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-10-but-3-ynyl-8, 8,12, 16-tetramethyl-3- (2-methyl-benzoxazole -5-yl) -4,17-dioxa-bicyclo [14. 1.0] heptadecane-5,9 dione;
(1 S, 3S, 7S, 10R, 11S, 12S, 16R) -7, 11-Dihydroxy-3- (2-hydroxymethyl-benzoxazol-5-yl) -10-but-3-ynyl-8, 8 , 12,16-Tetramethyl-4,17-dioxa-bicyclo [14.1.0] heptadecane-5,9 dione;
(1 S, 3 S, 7S, 1OR, 11 S, 12S, 16R) -3- (2-Aminomethyl-benzoxazol-5-yl) -7, 11-dihydroxy-10-but-3-ynyl-8 , 8,12, 16-tetramethyl-4,17-dioxa-bicyclo [14. 1. 0] selected from the group consisting of heptadecane-5,9-dione;
The joined body according to any one of claims 1 to 8, wherein a hydrogen atom in the effector element is substituted with L ¹ -L ^{3 at the} position represented by the formula (I).   10. The joined body according to any one of claims 1 to 9, wherein the joined body includes more than one recognition unit, and the recognition units are the same. The following formula (III ¹ )

[Wherein RG ¹ represents an O═C═N group, or an S═C═N group, or an O═C═N—CH ₂ group, or an S = C═N═CH ₂ group; and
R ^22a , R ^22b and EG have the meanings recited in claim 1]
A linker recognition unit represented by: or the following formula (III ² ):

[Wherein RG ² represents a HO—CH ₂ group or HNR ²³ —CH ₂ ; and
R ^22a , R ^22b and EG have the meanings recited in claim 1]
A linker recognition unit represented by the formula (wherein the following compound:
(4-hydroxymethyl) phenyl-2,3,4,6-tetra-0-acetyl-α-D-galactopyranoside;
(2-hydroxymethyl) phenyl-2,3,4,6-tetra-0-acetyl-α-D-galactopyranoside;
(4-hydroxymethyl) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester;
(2-hydroxymethyl) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester;
(4-hydroxymethyl) phenyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside;
(2-hydroxymethyl-4-nitro) phenyl-2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside;
(4-hydroxymethyl-2-nitro) phenyl-2,3,4,6-tetra-O-acetyl-α-D-galactopyranoside;
(2-hydroxymethyl-4-nitro) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester;
(4-hydroxymethyl-2-nitro) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester;
(2-chloro-4-hydroxymethyl) phenyl-2,3,4,6-tetra-0-acetyl-α-D-galactopyranoside;
(2-Chloro-4-hydroxymethyl) phenyl-2,3,4-tri-O-acetyl-β-D-glucuronide-6-methyl ester); or the following formula (III ³ ):

[Wherein, RG ³ represents a Hal-C (= O) -CH ₂ group, a Hal-C (= S) -CH ₂ group, or R ²⁷ -C (= O) -OC (= O) -CH ₂ Group, or R ²⁷ —C (═O) —OC (═S) —CH ₂ group, or the following formula:

Or a group represented by the following formula:

Represents a group represented by:
R ²⁷ is C ₁ -C ₁₀ -alkyl, aryl or aralkyl; and
R ^22a , R ^22b and EG have the meanings recited in claim 1]
A linker recognition unit represented by the formula (wherein the following compound:
2,5-dioxopyrrolidin-1-yl- [4- (2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl) -benzyl] carbonate;
2,5-dioxopyrrolidin-1-yl- [2- (2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl) -benzyl] carbonate;
2,5-dioxopyrrolidin-1-yl- [4-((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) -methyluronate) benzyl] carbonate;
4-nitrophenyl- [2-((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) methyluronate) -benzyl] carbonate;
2,5-dioxopyrrolidin-1-yl- [4- (2,3,4,6-tetra-0-acetyl-β-D-glucopyranosyl) -benzyl] carbonate;
4-nitrophenyl- [2- (2,3,4,6-tetra-0-acetyl-α-D-galactopyranosyl) -5-nitrobenzyl] carbonate;
4-nitrophenyl- [2-((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) methyluronate) -5-nitrobenzyl] carbonate;
4-nitrophenyl- [4-methoxy-5-nitro-2- ((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) methyluronate) benzyl] carbonate;
4-nitrophenyl- [4- ((2, 3, 4-tri-0-acetyl-β-D-glucopyranosyl) methyluronate) -5-nitrobenzyl] carbonate;
4-Chlorophenyl- [2-((2, 3, 4-tri-O-acetyl-β-D-glucopyranosyl) methyluronate) -5-nitrobenzyl] carbonate free). A method for producing a conjugate according to any one of claims 1 to 10, wherein the substituent is a compound of the general formula I having the meaning described in claim 1 (provided that at least one substituent L ^{The conditions in which 1} , L ² or L ⁴ represents a linker recognition unit of the general formula (III) need not be fulfilled and at least one substituent L ¹ , L ² or L ⁴ is hydrogen, a group C (═O) Cl or the group C (= S) Cl) is selected from the group consisting of linker recognition units of general formula (III ¹ ), or (III ² ), or (III ³ ) as described in claim 11 Reacting with a linker recognition unit to be reacted. General formula (I) (wherein the substituent has the meaning described in claim 1 provided that at least one substituent L ¹ , L ² or L ⁴ is a linker recognition unit of the general formula (III)) 13. The conditions representing the need not be satisfied and at least one substituent L ¹ , L ² or L ⁴ represents hydrogen, the group C (═O) Cl or the group C (+ S) Cl) Use for the method.   Use of a compound of general formula (I) for the production of a conjugate according to any one of claims 1-10. Use of a linker recognition unit of the general formula (III ¹ ), (III ² ) or (III ³ ) in the method according to claim 12. Use of a linker recognition unit of the general formula (III ¹ ), (III ² ) or (III ³ ) for the production of a conjugate according to any one of claims 1-10.   11. A joined body according to any one of claims 1 to 10 for use as a medicament.   11. A conjugate according to any one of claims 1 to 10 for use as a medicament for the treatment of diseases associated with the growth process.   19. The conjugate according to claim 18, wherein the disease is selected from the group consisting of tumor disease, inflammatory disease, neurodegenerative disease, angiogenesis-related disease, multiple sclerosis, Alzheimer's disease and rheumatoid arthritis.   11. A conjugate according to any one of claims 1 to 10 for the treatment of primary tumors and / or metastases that are not surgically accessible.   21. The conjugate of claim 20, wherein the conjugate is administered in combination of one or more substances to induce enhanced death (apoptosis) and necrosis.   21. The conjugate according to claim 20, wherein the conjugate is administered in combination with one or more substances selected from the group consisting of L19 structure, EDB-fibronectin and combrestatin A4 prodrug.