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【结 构 式】 
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【分子编号】40837 【品名】(4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione 【CA登记号】 |
【 分 子 式 】C27H41NO5S 【 分 子 量 】491.69228 【元素组成】C 65.96% H 8.4% N 2.85% O 16.27% S 6.52% |
合成路线1
该中间体在本合成路线中的序号：(XXVI)The silylation of the OH group of (XX) with TBDMS-triflate gives the fully silylated ketone (XXI), which is selectively monodesilylated with CSA in methanol/dichloromethane affording the primary alcohol (XXII). Oxidation of (XXII) first with Dess Martin periodinane (DMP) and then with NaClO2 provides the corresponding carboxylic acid (XXIII), which is again selectively desilylated with TBAF in THF to give the 15-hydroxy-5-oxoheptadecadienoic acid (XXIV). The cyclization of (XXIV) by means of DEC and DMAP in chloroform yields fully silylated Epothilon D (XXV), which is desilylated with HF/pyridine in THF to afford Epothilon D (XXVI). Finally, this compound is epoxidized with MCPBA in chloroform to afford the target Epothilon B.
| 【1】 Mulzer, J.; Ohler, E.; Mantoulidis, A. (Schering AG); Method for producing epothilone B and derivs., and intermediate products for this method. WO 0023452 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XX) | 40831 | (7S,10R,11S,12S,16Z,19S)-7-[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one | C45H87NO5SSi3 | 详情 | 详情 | |
| (XXI) | 40832 | (7S,10R,11S,12S,16Z,19S)-7,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,8,8,10,12,16,21,21,22,22-tridecamethyl-19-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,20-dioxa-3,21-disila-16-tricosen-9-one | C51H101NO5SSi4 | 详情 | 详情 | |
| (XXII) | 40833 | (5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one | C45H87NO5SSi3 | 详情 | 详情 | |
| (XXIII) | 40834 | (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C45H85NO6SSi3 | 详情 | 详情 | |
| (XXIV) | 40835 | (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (XXV) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XXVI) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIX)Compound (XXVIII) is deprotected with TFA in CH2Cl2 to provide the dihydroxymacrolactone (XXIX). Finally, this compound is epoxidated with methyl(trifluoromethyl)dioxirane (XXX) or MCPBA to furnish the target epothilone B.
| 【1】 Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXVIII) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XXIX) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 | |
| (XXX) | 43177 | 3-methyl-3-(trifluoromethyl)-1,2-dioxirane | C3H3F3O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXXV)The fully silylation of (XXX) with Tbdms-OTf and lutidine in dichloromethane gives the tetrasilyloxy compound (XXXI). The stepwise desilylation first with K2CO3 in methanol to yield the carboxylic acid (XXXII), and then with TBAF in THF, affords the hydroxyacid (XXXIII). The macrolactonization of (XXXIII) was carried out with the Yamaguchi method using 2,4,6-trichlorobenzoyl chloride, TEA and DMAP in THF to yield the silylated macrolactone (XXXIV), which is deprotected with TFA in dichloromethane to afford the dihydroxymacrolactone (XXXV). Finally, the double bond of (XXXV) is epoxidated with methyl(trifluoromethyl)dioxirane (XXXVI) in acetonitrile to provide the target epothilone B.
| 【1】 Nicolaou, K.C.; et al.; Total syntheses of epothilones A and B via a macrolactonization-based strategy. J Am Chem Soc 1997, 119, 34, 7974. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXX) | 46118 | (3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (XXXI) | 46119 | tert-butyl(dimethyl)silyl (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate | C51H99NO6SSi4 | 详情 | 详情 | |
| (XXXII) | 40834 | (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C45H85NO6SSi3 | 详情 | 详情 | |
| (XXXIII) | 40835 | (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (XXXIV) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XXXV) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 | |
| (XXXVI) | 43177 | 3-methyl-3-(trifluoromethyl)-1,2-dioxirane | C3H3F3O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XXXVII)Assembly of the target compound: The condensation of intermediates (XXI) and (XXXIII) by means of 9-BBN, a PdCl2 catalyst and K3PO4 in hot DMF/water gives the adduct (XXXIV), which is hydrolyzed with NaOH in methanol/water to yield the hydroxyacid (XXXV). The macrolactonization of (XXXV) by the Yamaguchi procedure using 2,4,6-trichlorobenzoyl chloride, TEA and DMAP in THF affords the macrolactone (XXXVI), which is desilylated with HF and pyridine in THF, furnishing the dihydroxylactone (XXXVII). Finally, this compound is epoxidated by means of dimethyldioxirane (XXXVIII) in dichloromethane to give the target epothilone B.
| 【1】 Sawada, D.; et al.; Enantioselective total synthesis of epothilones A and B using multifunctional asymmetric catalysis. J Am Chem Soc 2000, 122, 43, 10521. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXI) | 44519 | phenyl (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-10-undecenoate | C33H58O5Si2 | 详情 | 详情 | |
| (XXXIII) | 46125 | (1S,3Z)-4-iodo-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl acetate | C14H18INO2S | 详情 | 详情 | |
| (XXXIV) | 46126 | phenyl (3S,6R,7S,8S,12Z,15S,16E)-15-(acetoxy)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoate | C47H77NO7SSi2 | 详情 | 详情 | |
| (XXXV) | 40835 | (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (XXXVI) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XXXVII) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 | |
| (XXXVIII) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XXXVI)Hydrolysis of the dimethylacetal group of (XXVIII) with Ts-OH in dioxane/water yields the corresponding aldehyde (XXIX), which is submitted to an intramolecular aldolization by means of KHMDS in THF to afford a mixture of diastereomeric macrolactones (XXX) and (XXXI). The undesired isomer (XXX) was recovered, oxidized with DMP to the ketone (XXXII) and reduced again with NaBH4 to provide high yields of the desired isomer (XXXI). Selective desilylation of (XXXI) with HF/pyridine in THF gives the diol (XXXIII), which is selectively monosilylated with Tbdms-OTf and lutidine in dichloromethane, yielding the bis-silylated triol (XXXIV). The oxidation of the free OH group of (XXXIV) with DMP in dichloromethane affords the corresponding ketonic derivative (XXXV), which is deprotected with HF/pyridine in THF, providing the free dihydroxy compound (XXXVI). Finally, this compound is epoxidized by means of dimethyldioxirane (DMDO) in dichloromethane to afford the target epothilone B.
| 【1】 Meng, D.; et al.; Total syntheses of epothilones A and B. J Am Chem Soc 1997, 119, 42, 10073. |
| 【2】 Bertinato, P.; Danishefsky, S.J.; Su, D.-S.; Kamenecka, T.; Meng, D.F.; Sorensen, E.J.; Savin, K.A.; Chou, T.-C.; Balog, A. (Sloan-Kettering Institute); Synthesis of epothilones, intermediates thereto, analogues and uses thereof. JP 2001507716; US 6242469; WO 9901124 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXVIII) | 46127 | (1S,3Z,8S,9S,10R,11R)-9-[[tert-butyl(dimethyl)silyl]oxy]-13,13-dimethoxy-4,8,10,12,12-pentamethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-11-[(triphenylsilyl)oxy]-3-tridecenyl acetate | C53H77NO6SSi2 | 详情 | 详情 | |
| (XXIX) | 46128 | (1S,3Z,8S,9S,10R,11R)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8,10,12,12-pentamethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-13-oxo-11-[(triphenylsilyl)oxy]-3-tridecenyl acetate | C51H71NO5SSi2 | 详情 | 详情 | |
| (XXX) | 46129 | (4R,6R,7R,8S,9S,16S)-8-[[tert-butyl(dimethyl)silyl]oxy]-4-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-6-[(triphenylsilyl)oxy]oxa-13-cyclohexadecen-2-one | C51H71NO5SSi2 | 详情 | 详情 | |
| (XXXI) | 46130 | (4S,6R,7R,8S,9S,16S)-8-[[tert-butyl(dimethyl)silyl]oxy]-4-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-6-[(triphenylsilyl)oxy]oxa-13-cyclohexadecen-2-one | C51H71NO5SSi2 | 详情 | 详情 | |
| (XXXII) | 46131 | (6R,7R,8S,9S,16S)-8-[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-6-[(triphenylsilyl)oxy]oxa-13-cyclohexadecene-2,4-dione | C51H69NO5SSi2 | 详情 | 详情 | |
| (XXXIII) | 46132 | (4S,6R,7S,8S,9S,16S)-8-[[tert-butyl(dimethyl)silyl]oxy]-4,6-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecen-2-one | C33H57NO5SSi | 详情 | 详情 | |
| (XXXIV) | 46133 | (4S,6R,7S,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-6-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecen-2-one | C39H71NO5SSi2 | 详情 | 详情 | |
| (XXXV) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XXXVI) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XI)The condensation of the phosphonium salt (I) with the ketone (II) by means of NaHMDS in THF gives the diene (III), which is selectively monodeprotected with CSA in methanol/dichloromethane to yield the primary alcohol (IV). The oxidation of (IV) with SO3/pyridine affords the corresponding aldehyde (V), which is condensed with the ketoacid (VI) by means of LDA in THF to provide the heptadienoic acid (VII). The protection of the OH group of (VII) y means of Tbdms-OTf and lutidine in dichloromethane gives the fully silylated compound (VIII), which is selectively monodeprotected with TBAF in THF to yield the hydroxyacid (IX). The macrolactonization of (IX) by means of 2,4,6-trichlorobenzoyl chloride and TEA in THF affords the macrolactone (X), which is deprotected with TFA in dichloromethane to provide the precursor (XI). Finally, this compound is epoxidized by means of methyl(trifluoromethyl)dioxirane in acetonitrile to furnish the target epothilone B.
| 【1】 Nicolaou, K.C.; et al.; Synthesis of epothilones A and B in solid and solution phase. Nature 1997, 387, 6630, 268. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 44459 | [(3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)-4-pentenyl](triphenyl)phosphonium iodide | C34H43INOPSSi | 详情 | 详情 | |
| (II) | 46121 | (6S)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-methyl-2-heptanone | C14H30O2Si | 详情 | 详情 | |
| (III) | 40827 | tert-butyl(dimethyl)silyl (1S,3Z,8S)-9-[[tert-butyl(dimethyl)silyl]oxy]-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-nonenyl ether; 4-((1E,3S,5Z,10S)-3,11-bis[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-1,5-undecadienyl)-2-methyl-1,3-thiazole | C30H57NO2SSi2 | 详情 | 详情 | |
| (IV) | 40828 | (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol | C24H43NO2SSi | 详情 | 详情 | |
| (V) | 40829 | (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal | C24H41NO2SSi | 详情 | 详情 | |
| (VI) | 43166 | (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid | C15H30O4Si | 详情 | 详情 | |
| (VII) | 46118 | (3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (VIII) | 40834 | (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C45H85NO6SSi3 | 详情 | 详情 | |
| (IX) | 40835 | (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (X) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XI) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 | |
| (XII) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(XXXV)The selective monodesilylation of (XXXII) with TBAF in THF gives the hydroxyacid (XXXIII), which is submitted to a macrolactonization by means of EDC and DMAP in chloroform to yield the macrolactone (XXXIV). The desilylation of (XXXIV) with HF in pyridine/THF affords the dihydroxy macrolactone (XXXV), which is finally epoxidized by means of MCPBA in chloroform to furnish the target epothilone B.
| 【1】 Mulzer, J.; et al.; Total synthesis of epothilones B and D. J Org Chem 2000, 65, 22, 7456. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXII) | 40834 | (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C45H85NO6SSi3 | 详情 | 详情 | |
| (XXXIII) | 40835 | (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (XXXIV) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XXXV) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(XXXI)The macrolactonization of (XXVIII) by means of 2,4,6-trichlorobenzoyl chloride and TEA in THF provides the protected macrolactone (XXIX), which is deprotected with TFA in dichloromethane to give the trienic macrolactone (XXX). Selective hydrogenation of the disubstituted double bond of (XXX) by means of potassium azodicarboxylate (DKAD) and AcOH in dichloromethane yields the precursor (XXXI), which is finally epoxidized with dimethyldioxirane (XXXII) in dichloromethane to afford the target epothilone B.
| 【1】 White, J.D.; Carter, R.G.; Sundermann, K.F.; Wartmann, M.; Total synthesis of epothilone B, epothilone D, and cis- and trans-9,10-dehydroepothilone D. J Am Chem Soc 2001, 123, 23, 5407. |
| 【2】 White, J.D.; et al.; A highly stereoselective synthesis of epothilone B. J Org Chem 1999, 64, 3, 684. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXVIII) | 46158 | (3S,6R,7S,8S,9Z,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-9,12,16-heptadecatrienoic acid | C39H69NO6SSi2 | 详情 | 详情 | |
| (XXIX) | 46159 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-10,13-cyclohexadecadiene-2,6-dione | C39H67NO5SSi2 | 详情 | 详情 | |
| (XXX) | 46160 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-10,13-cyclohexadecadiene-2,6-dione | C27H39NO5S | 详情 | 详情 | |
| (XXXI) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 | |
| (XXXII) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(XI)The reaction of chiral aldehyde (I) with dimethyl diazomethylphosphonate (II) by means of tBu-OK in THF gives the acetylenic ester (III), which is condensed with ally bromide derivative (IV) by means of CuI and TEA in DMF/ethyl ether to yield the dienyne (V). The partial hydrogenation of (V) over a Lindlar catalyst in hexane affords the trienoic ester (VI). The hydrolysis of (VI) with NaOH in warm isopropanol provides the corresponding carboxylic acid (VII), which is selectively desilylated with TBAF in THF to give the hydroxyacid (VIII). The macrolactonization of (VIII) by means of 2,4,6-trichlorobenzoyl chloride and TEA in benzene/THF yields the protected macrolactone (IX), which is deprotected with TFA in dichloromethane to afford the trienic macrolactone (X). Selective hydrogenation of the disubstituted double bond of (X) by means of potassium azodicarboxylate (DKAD) and HOAc in dichloromethane provides the precursor (XI), which is finally epoxidated with dimethyldioxirane (XII) in dichloromethane to furnish the target epothilone B.
| 【1】 White, J.D.; et al.; Improved synthesis of epothilone B employing alkylation of an alkyne for assembly of subunits. Org Lett 1999, 1, 9, 1431. |
| 【2】 White, J.D.; et al.; A highly stereoselective synthesis of epothilone B. J Org Chem 1999, 64, 3, 684. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 46155 | methyl (3S,6R,7S,8R)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5,9-dioxononanoate | C26H52O6Si2 | 详情 | 详情 | |
| (II) | 42709 | Diazomethylphoshonic acid dimethyl ester | 27491-70-9 | C3H7N2O3P | 详情 | 详情 |
| (III) | 46161 | methyl (3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-9-decynoate | C27H52O5Si2 | 详情 | 详情 | |
| (IV) | 46147 | 4-((1E,3S,5Z)-7-bromo-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6-dimethyl-1,5-heptadienyl)-2-methyl-1,3-thiazole; (1S,3Z)-5-bromo-4-methyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3-pentenyl tert-butyl(dimethyl)silyl ether | C19H32BrNOSSi | 详情 | 详情 | |
| (V) | 46162 | methyl (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadien-9-ynoate | C46H83NO6SSi3 | 详情 | 详情 | |
| (VI) | 46156 | methyl (3S,6R,7S,8S,9Z,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-9,12,16-heptadecatrienoate | C46H85NO6SSi3 | 详情 | 详情 | |
| (VII) | 46157 | (3S,6R,7S,8S,9Z,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-9,12,16-heptadecatrienoic acid | C45H83NO6SSi3 | 详情 | 详情 | |
| (VIII) | 46158 | (3S,6R,7S,8S,9Z,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-9,12,16-heptadecatrienoic acid | C39H69NO6SSi2 | 详情 | 详情 | |
| (IX) | 46159 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-10,13-cyclohexadecadiene-2,6-dione | C39H67NO5SSi2 | 详情 | 详情 | |
| (X) | 46160 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-10,13-cyclohexadecadiene-2,6-dione | C27H39NO5S | 详情 | 详情 | |
| (XI) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 | |
| (XII) | 31501 | 3,3-dimethyl-1,2-dioxirane | C3H6O2 | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(XXIV)The oxidation of alcohol (XX) with PCC and NaClO2 gives the carboxylic acid (XXI), which is regioselectively monodesilylated with TBAF, yielding the hydroxyacid (XXII). The macrolactonization of (XXII) under Yamaguchi conditions (2,4,6-trichlorobenzoyl chloride) affords the macrolactone (XXIII), which is desilylated with HF and pyridine to provide the precursor (XXIV). Finally, this compound is epoxidated with MCPBA to afford the target epothilone B.
| 【1】 Chen, Y.; Taylor, R.E.; Total synthesis of epothilones B and D. Org Lett 2001, 3, 14, 2221. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XX) | 40833 | (5S,8R,9S,10S,14Z,17S)-9-[[tert-butyl(dimethyl)silyl]oxy]-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,10,14,19,19,20,20-tridecamethyl-17-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,18-dioxa-3,19-disila-14-henicosen-7-one | C45H87NO5SSi3 | 详情 | 详情 | |
| (XXI) | 40834 | (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C45H85NO6SSi3 | 详情 | 详情 | |
| (XXII) | 40835 | (3S,6R,7S,8S,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (XXIII) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XXIV) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(XXIV)The treatment of (XVIII) with Troc-Cl and pyridine gives fully protected (XIX) as the same diastereomeric mixture, which is selectively deprotected at the Sem group with TFA in dichloromethane to yield the corresponding mixture of hydroxyacids (XX). The macrolactonization of (XX) by the Yamaguchi method (2,4,6-trichlrobenzoyl chloride, TEA and DMAP in toluene) gives the diastereomeric mixture of lactones (XXI), which are readily separated by flash column chromatography. The desired diastereomer (XXII) is desilylated with HF and pyridine, yielding the hydroxylactone (XXIII), which is treated with Zn and NH4Cl in refluxing aqueous methanol to eliminate the Troc protecting group and provide the unprotected precursor (XXIV). Finally, this compound is epoxidated with methyl(trifluoromethyl)dioxirane (MTFDO) to afford the target epothilone B.
| 【1】 Valluri, M.; et al.; Total synthesis of epothilone B. Org Lett 2001, 3, 23, 3607. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIIIa) | 52584 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-15-[({[2-(trimethyl-lambda~4~-sulfanyl)ethyl]oxy}methyl)oxy]-12,16-heptadecadienoic acid | C39H71NO7S2Si | 详情 | 详情 | |
| (XVIIIb) | 52585 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-15-[({[2-(trimethyl-lambda~4~-sulfanyl)ethyl]oxy}methyl)oxy]-12,16-heptadecadienoic acid | C39H71NO7S2Si | 详情 | 详情 | |
| (XIXa) | 52586 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-({[(2,2,2-trichloroethyl)oxy]carbonyl}oxy)-15-[({[2-(trimethyl-lambda~4~-sulfanyl)ethyl]oxy}methyl)oxy]-12,16-heptadecadienoic acid | C42H72Cl3NO9S2Si | 详情 | 详情 | |
| (XIXb) | 52587 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-({[(2,2,2-trichloroethyl)oxy]carbonyl}oxy)-15-[({[2-(trimethyl-lambda~4~-sulfanyl)ethyl]oxy}methyl)oxy]-12,16-heptadecadienoic acid | C42H72Cl3NO9S2Si | 详情 | 详情 | |
| (XXa) | 52588 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-({[(2,2,2-trichloroethyl)oxy]carbonyl}oxy)-12,16-heptadecadienoic acid | C36H58Cl3NO8SSi | 详情 | 详情 | |
| (XXb) | 52589 | 3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-({[(2,2,2-trichloroethyl)oxy]carbonyl}oxy)-12,16-heptadecadienoic acid | C36H58Cl3NO8SSi | 详情 | 详情 | |
| (XXIa),(XXII) | 52590 | 4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-2,6-dioxooxa-13-cyclohexadecen-8-yl 2,2,2-trichloroethyl carbonate | C36H56Cl3NO7SSi | 详情 | 详情 | |
| (XXIb) | 52591 | 4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-2,6-dioxooxa-13-cyclohexadecen-8-yl 2,2,2-trichloroethyl carbonate | C36H56Cl3NO7SSi | 详情 | 详情 | |
| (XXIII) | 52592 | 4-hydroxy-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-2,6-dioxooxa-13-cyclohexadecen-8-yl 2,2,2-trichloroethyl carbonate | C30H42Cl3NO7S | 详情 | 详情 | |
| (XXIV) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(XVI)The reaction of 4-methyl-4-penten-1-ol (I) with PBr3 gives the corresponding alkyl bromide (II), which is condensed with epoxide (III) and propyne (IV) by means of Mg, CuI and pentynyl lithium to yield, after silylation with Tbdms-Cl, the protected diol (V). The selective deprotection of (V) with DDQ gives the secondary alcohol (VI), which is oxidized by the Swern reagent to afford the ketone (VII). Alternatively, ketone (VII) can also be obtained by direct oxidation of the protected diol (V) with the Jones reagent. The Horner Emmons condensation of ketone (VII) with phosphonate (VIII) provides the unsaturated alkyl thiazole (IX), which is treated with (Ipc)2BH and sodium formate in THF to give the secondary alcohol (X). The oxidation of (X) with the complex SO3/Pyr yields the carbaldehyde (XI). Alternatively, (XI) can also be obtained by direct oxidation of the terminal double bond of (IX) with (Ipc)2BH and pyridinium chlorochromate (PCC). The condensation of aldehyde (XI) with ketoacid (XII) by means of LDA in THF affords the heptadecadienoic acid (XIII), which is silylated with Tbdms-OTf to provide the protected linear precursor (XIV). The cyclization of (XIV) by means of 2,4,6-trichlorobenzoyl chloride and DMAP in pyridine gives the protected cyclic precursor (XV), which is desilylated by means of TBAF in THF to yield the unprotected precursor (XVI). Finally, this compound is epoxidated by means of dimethyldioxirane (DMDO) in acetone to afford the target epothilone B.
| 【1】 Avery, M.A. (University of Mississippi); Synthesis of epothilones and related analogs. WO 0230356 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 54285 | 4-methyl-4-penten-1-ol | 22508-64-1 | C6H12O | 详情 | 详情 |
| (II) | 52575 | 5-bromo-2-methyl-1-pentene | C6H11Br | 详情 | 详情 | |
| (III) | 52578 | methyl 4-({[1-(2-oxiranyl)ethyl]oxy}methyl)phenyl ether; 2-[1-({[4-(methyloxy)phenyl]methyl}oxy)ethyl]oxirane | C2H5NS | 详情 | 详情 | |
| (IV) | 51602 | 1-Propyne | C3H4 | 详情 | 详情 | |
| (V) | 54286 | tert-butyl(dimethyl)silyl (1S,3Z)-1-{(1R)-1-[(4-methoxybenzyl)oxy]ethyl}-4,8-dimethyl-3,8-nonadienyl ether; tert-butyl[((1S,3Z)-1-{(1R)-1-[(4-methoxybenzyl)oxy]ethyl}-4,8-dimethyl-3,8-nonadienyl)oxy]dimethylsilane | n/a | C27H46O3Si | 详情 | 详情 |
| (VI) | 54287 | (2R,3S,5Z)-3-{[tert-butyl(dimethyl)silyl]oxy}-6,10-dimethyl-5,10-undecadien-2-ol | n/a | C19H38O2Si | 详情 | 详情 |
| (VII) | 54288 | (3S,5Z)-3-{[tert-butyl(dimethyl)silyl]oxy}-6,10-dimethyl-5,10-undecadien-2-one | n/a | C19H36O2Si | 详情 | 详情 |
| (VIII) | 44442 | diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C9H16NO3PS | 详情 | 详情 | |
| (IX) | 54289 | tert-butyl(dimethyl)silyl (1S,3Z)-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3,8-nonadienyl ether; 4-((1E,3S,5Z)-3-{[tert-butyl(dimethyl)silyl]oxy}-2,6,10-trimethyl-1,5,10-undecatrienyl)-2-methyl-1,3-thiazole | n/a | C24H41NOSSi | 详情 | 详情 |
| (X) | 40828 | (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadien-1-ol | C24H43NO2SSi | 详情 | 详情 | |
| (XI) | 40829 | (2S,6Z,9S,10E)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-6,10-undecadienal | C24H41NO2SSi | 详情 | 详情 | |
| (XII) | 43166 | (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid | C15H30O4Si | 详情 | 详情 | |
| (XIII) | 46118 | (3S,6R,7S,8S,12Z,15S,16E)-3,15-bis[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C39H71NO6SSi2 | 详情 | 详情 | |
| (XIV) | 40834 | (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-tris[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | C45H85NO6SSi3 | 详情 | 详情 | |
| (XV) | 40836 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (XVI) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线13
该中间体在本合成路线中的序号：(XV)The condensation of 3-buten-2-one (I) with the phosphonate (II) by means of LDA gives the alkylated thiazole (III), which is enantioselectively epoxidated to the chiral oxirane (V) by means of oxone and the chiral ketone (IV). Alternatively, the oxidation of the chiral epoxybutanol (VI) with CrO3 or SO3 /pyridine yields the epoxybutanone (VII), which is condensed with phosphorane (II) by means of LDA to afford the already reported chiral oxirane (V). The condensation of (V) with alkyl bromide (VIII) and propyne (IX) by means of Mg, CuBr and pentynyl lithium provides the undecatrienyl thiazole (X), which is treated with Tms-OTf in order to protect its OH group, yielding the silyl ether (XI). The oxidation of the terminal double bond of (XI) by means of (Ipc)2BH and CrO3 affords the carbaldehyde (XII), which is condensed with ketoacid (XIII) by means of LDA in THF to provide the undecadienoic acid (XIV). The cyclization of (XIV) by means of benzenesulfonyl chloride and pyridine gives the macrocyclic intermediate (XV), which is finally epoxidated by means of DMDO in acetone to furnish the target epothilone B.
| 【1】 Avery, M.A. (University of Mississippi); Synthesis of epothilones and related analogs. WO 0230356 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 54294 | 1-pentynyllithium | n/a | C5H7Li | 详情 | 详情 | |
| (I) | 30324 | 3-buten-2-one; methyl vinyl ketone | 78-94-4 | C4H6O | 详情 | 详情 |
| (II) | 44442 | diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C9H16NO3PS | 详情 | 详情 | |
| (III) | 54290 | 2-methyl-4-[(1E)-2-methyl-1,3-butadienyl]-1,3-thiazole | n/a | C9H11NS | 详情 | 详情 |
| (IV) | 54291 | n/a | C13H20O5 | 详情 | 详情 | |
| (V) | 54293 | 2-methyl-4-{(E)-2-[(2R)oxiranyl]-1-propenyl}-1,3-thiazole | n/a | C9H11NOS | 详情 | 详情 |
| (VI) | 52597 | 1-(2-oxiranyl)-1-ethanol | C4H8O2 | 详情 | 详情 | |
| (VII) | 54292 | 1-[(2R)oxiranyl]-1-ethanone | n/a | C4H6O2 | 详情 | 详情 |
| (VIII) | 52575 | 5-bromo-2-methyl-1-pentene | C6H11Br | 详情 | 详情 | |
| (IX) | 51602 | 1-Propyne | C3H4 | 详情 | 详情 | |
| (X) | 54295 | (1E,3S,5Z)-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,5,10-undecatrien-3-ol | n/a | C18H27NOS | 详情 | 详情 |
| (XI) | 54296 | 2-methyl-4-{(1E,3S,5Z)-2,6,10-trimethyl-3-[(trimethylsilyl)oxy]-1,5,10-undecatrienyl}-1,3-thiazole; (1S,3Z)-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3,8-nonadienyl trimethylsilyl ether | n/a | C21H35NOSSi | 详情 | 详情 |
| (XII) | 54297 | (2S,6Z,9S,10E)-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-9-[(trimethylsilyl)oxy]-6,10-undecadienal | n/a | C21H35NO2SSi | 详情 | 详情 |
| (XIII) | 52596 | 3-hydroxy-4,4-dimethyl-5-oxoheptanoic acid | C9H16O4 | 详情 | 详情 | |
| (XIV) | 54298 | (3S,6R,7S,8S,12Z,15S,16E)-3,7,15-trihydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-12,16-heptadecadienoic acid | n/a | C27H43NO6S | 详情 | 详情 |
| (XV) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线14
该中间体在本合成路线中的序号：(XVII)The condensation of alkyl bromide (I) with epoxide (II) and propyne (III) by means of Mg, CuI and pentynyl lithium gives the secondary alcohol (IV), which is silylated with Sem-Cl to yield the protected diol (V). The selective deprotection of (V) with DDQ gives the secondary alcohol (VI), which is oxidized by means of SO3 /pyridine to afford the ketone (VII). The condensation of ketone (VII) with phosphonate (VIII) by means of BuLi in THF provides the unsaturated alkyl thiazole (IX), which is treated with (Ipc)2BH and sodium formate in THF to give the secondary alcohol (X). The oxidation of (X) with oxalyl chloride yields the carbaldehyde (XI), which is condensed with ketoacid (XII) by means of LDA in THF to afford the heptadecadienoic acid (XIII). The protection of the free OH group of (XIII) with Troc-Cl and DMAP in dichloromethane provides the protected linear precursor (XIV), which is selectively monodeprotected with TFA in dichloromethane to furnish the linear hydroxyacid (XV). The macrocyclization of (XV) by means of 2,4,6-trichlorobenzoyl chloride and DMAP in pyridine gives the protected cyclic precursor (XVI), which is deprotected first with HF and pyridine (desilylation), and then with Zn and HOAc (elimination of the Troc protecting group), to yield the unprotected precursor (XVII). Finally, this compound is epoxidated by means of dimethyldioxirane (DMDO) in acetone to afford the target epothilone B.
| 【1】 Avery, M.A. (University of Mississippi); Synthesis of epothilones and related analogs. WO 0230356 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 52575 | 5-bromo-2-methyl-1-pentene | C6H11Br | 详情 | 详情 | |
| (II) | 52578 | methyl 4-({[1-(2-oxiranyl)ethyl]oxy}methyl)phenyl ether; 2-[1-({[4-(methyloxy)phenyl]methyl}oxy)ethyl]oxirane | C2H5NS | 详情 | 详情 | |
| (III) | 51602 | 1-Propyne | C3H4 | 详情 | 详情 | |
| (IV) | 54286 | tert-butyl(dimethyl)silyl (1S,3Z)-1-{(1R)-1-[(4-methoxybenzyl)oxy]ethyl}-4,8-dimethyl-3,8-nonadienyl ether; tert-butyl[((1S,3Z)-1-{(1R)-1-[(4-methoxybenzyl)oxy]ethyl}-4,8-dimethyl-3,8-nonadienyl)oxy]dimethylsilane | n/a | C27H46O3Si | 详情 | 详情 |
| (V) | 54299 | (3R,4S)-4-[(2Z)-3,7-dimethyl-2,7-octadienyl]-1-(4-methoxyphenyl)-3,10,10-trimethyl-2,5,7-trioxa-10-silaundecane; 4-{(3R,4S)-4-[(2Z)-3,7-dimethyl-2,7-octadienyl]-3,10,10-trimethyl-2,5,7-trioxa-10-silaundec-1-yl}phenyl methyl ether | n/a | C27H46O4Si | 详情 | 详情 |
| (VI) | 54300 | (2R,3S,5Z)-6,10-dimethyl-3-{[2-(trimethylsilyl)ethoxy]methoxy}-5,10-undecadien-2-ol | n/a | C19H38O3Si | 详情 | 详情 |
| (VII) | 54301 | (3S,5Z)-6,10-dimethyl-3-{[2-(trimethylsilyl)ethoxy]methoxy}-5,10-undecadien-2-one | n/a | C19H36O3Si | 详情 | 详情 |
| (VIII) | 44442 | diethyl (2-methyl-1,3-thiazol-4-yl)methylphosphonate | C9H16NO3PS | 详情 | 详情 | |
| (IX) | 54302 | 2-methyl-4-((1E,3S,5Z)-2,6,10-trimethyl-3-{[2-(trimethylsilyl)ethoxy]methoxy}-1,5,10-undecatrienyl)-1,3-thiazole; (1S,3Z)-4,8-dimethyl-1-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-3,8-nonadienyl [2-(trimethylsilyl)ethoxy]methyl ether | n/a | C24H41NO2SSi | 详情 | 详情 |
| (X) | 54303 | (2S,6Z,9S,10E)-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-9-{[2-(trimethylsilyl)ethoxy]methoxy}-6,10-undecadien-1-ol | n/a | C24H43NO3SSi | 详情 | 详情 |
| (XI) | 54304 | (2S,6Z,9S,10E)-2,6,10-trimethyl-11-(2-methyl-1,3-thiazol-4-yl)-9-{[2-(trimethylsilyl)ethoxy]methoxy}-6,10-undecadienal | n/a | C24H41NO3SSi | 详情 | 详情 |
| (XII) | 43166 | (3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-5-oxoheptanoic acid | C15H30O4Si | 详情 | 详情 | |
| (XIII) | 54305 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-7-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-15-{[2-(trimethylsilyl)ethoxy]methoxy}-12,16-heptadecadienoic acid | n/a | C39H71NO7SSi2 | 详情 | 详情 |
| (XIV) | 54306 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-15-{[2-(trimethylsilyl)ethoxy]methoxy}-12,16-heptadecadienoic acid | n/a | C42H72Cl3NO9SSi2 | 详情 | 详情 |
| (XV) | 54307 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-12,16-heptadecadienoic acid | n/a | C36H58Cl3NO8SSi | 详情 | 详情 |
| (XVI) | 52590 | 4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-2,6-dioxooxa-13-cyclohexadecen-8-yl 2,2,2-trichloroethyl carbonate | C36H56Cl3NO7SSi | 详情 | 详情 | |
| (XVII) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线15
该中间体在本合成路线中的序号：(XLIV)The oxidation of (XXXVIII) with TPAP and NMO in acetonitrile gives the carbaldehyde (XXXIX), which is condensed with the intermediate phosphonium bromide (XVII) by means of LiHMDS in THF to yield the heptadecadienoic ester (XL). The regioselective deprotection of (XL) by means of Tms-OTf in dichloromethane affords the hydroxyacid (XLI), which is submitted to a macrocyclization by means of 2,4,6-trichlorobenzoyl chloride and TEA in THF to provide the protected didehydro precursor (XLII). The desilylation of (XLII) by means of TFA in dichloromethane yields the free didehydro precursor (XLIII), which is hydrogenated by means of 2,4,6-tri-isopropylbenzenesulfonyl hydrazide and TEA in refluxing ethyl ether to afford epothilone D (XLIII). Finally, this compound is epoxidated by means of dimethyldioxirane (DMDO) in dichloromethane.
| 【1】 Potier, P.; Ermolenko, M.S.; Synthesis of epothilones B and D from D-glucose. Tetrahedron Lett 2002, 43, 16, 2895. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 46148 | [(3Z,6S,7E)-6-[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-8-(2-methyl-1,3-thiazol-4-yl)-3,7-octadienyl](triphenyl)phosphonium bromide | C38H49BrNOPSSi | 详情 | 详情 | |
| (XXXVIII) | 54362 | tert-butyl (3S,6R,7S,8S)-3,7-bis{[tert-butyl(dimethyl)silyl]oxy}-9-hydroxy-4,4,6,8-tetramethyl-5-oxononanoate | C29H60O6Si2 | 详情 | 详情 | |
| (XXXIX) | 54363 | tert-butyl (3S,6R,7S,8R)-3,7-bis{[tert-butyl(dimethyl)silyl]oxy}-4,4,6,8-tetramethyl-5,9-dioxononanoate | C29H58O6Si2 | 详情 | 详情 | |
| (XL) | 54364 | tert-butyl (3S,6R,7S,8S,9Z,12Z,15S,16E)-3,7,15-tris{[tert-butyl(dimethyl)silyl]oxy}-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-9,12,16-heptadecatrienoate | C49H91NO6SSi3 | 详情 | 详情 | |
| (XLI) | 46158 | (3S,6R,7S,8S,9Z,12Z,15S,16E)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-9,12,16-heptadecatrienoic acid | C39H69NO6SSi2 | 详情 | 详情 | |
| (XLII) | 46159 | (4S,7R,8S,9S,16S)-4,8-bis[[tert-butyl(dimethyl)silyl]oxy]-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-10,13-cyclohexadecadiene-2,6-dione | C39H67NO5SSi2 | 详情 | 详情 | |
| (XLIII) | 46160 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-10,13-cyclohexadecadiene-2,6-dione | C27H39NO5S | 详情 | 详情 | |
| (XLIV) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线16
该中间体在本合成路线中的序号：(XXIX)The selective cleavage of the Sem protecting group of (XXV) by means of MgBr2, MeNO2 and BuSH gives the hydroxyacid (XXVI), which is submitted to macrolactonization by means of 2,4,6-trichlorobenzoyl chloride and TEA in THF to yield the protected macrolactone (XXVII). The treatment of (XXVII) with Zn and NH4Cl cleaves the Troc protecting group of to yield lactone (XXVIII), which is treated with HF and pyridine to afford epothilone D (XXIX). Finally, this compound is epoxidated by means of MCPBA or DMDO to provide the target epothilone B.
| 【1】 Jung, J.-K.; Kache, R.; Vines, K.K.; Zheng, Y.-S.; Avery, M.A.; Total synthesis of epothilones B and D amenable to large-scale preparation. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXV) | 54306 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-15-{[2-(trimethylsilyl)ethoxy]methoxy}-12,16-heptadecadienoic acid | n/a | C42H72Cl3NO9SSi2 | 详情 | 详情 |
| (XXVI) | 54307 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-12,16-heptadecadienoic acid | n/a | C36H58Cl3NO8SSi | 详情 | 详情 |
| (XXVII) | 52590 | 4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-2,6-dioxooxa-13-cyclohexadecen-8-yl 2,2,2-trichloroethyl carbonate | C36H56Cl3NO7SSi | 详情 | 详情 | |
| (XXVIII) | 63911 | (4S,7R,8S,9S,16S)-4-{[tert-butyl(dimethyl)silyl]oxy}-8-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C33H55NO5SSi | 详情 | 详情 | |
| (XXIX) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线17
该中间体在本合成路线中的序号：(XXIX)The selective cleavage of the Sem protecting group of (XXV) by means of MgBr2, MeNO2 and BuSH gives the hydroxyacid (XXVI), which is submitted to macrolactonization by means of 2,4,6-trichlorobenzoyl chloride and TEA in THF to yield the protected macrolactone (XXVII). The treatment of (XXVII) with Zn and NH4Cl cleaves the Troc protecting group of(XXVII) to yield lactone (XVIII), which is finally treated with HF and pyridine to afford the target epothilone D
| 【1】 Jung, J.-K.; Kache, R.; Vines, K.K.; Zheng, Y.-S.; Avery, M.A.; Total synthesis of epothilones B and D amenable to large-scale preparation. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 121. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXV) | 54306 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-15-{[2-(trimethylsilyl)ethoxy]methoxy}-12,16-heptadecadienoic acid | n/a | C42H72Cl3NO9SSi2 | 详情 | 详情 |
| (XXVI) | 54307 | (3S,6R,7S,8S,12Z,15S,16E)-3-{[tert-butyl(dimethyl)silyl]oxy}-15-hydroxy-4,4,6,8,12,16-hexamethyl-17-(2-methyl-1,3-thiazol-4-yl)-5-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-12,16-heptadecadienoic acid | n/a | C36H58Cl3NO8SSi | 详情 | 详情 |
| (XXVII) | 52590 | 4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5,5,7,9,13-pentamethyl-16-[1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-2,6-dioxooxa-13-cyclohexadecen-8-yl 2,2,2-trichloroethyl carbonate | C36H56Cl3NO7SSi | 详情 | 详情 | |
| (XXVIII) | 63911 | (4S,7R,8S,9S,16S)-4-{[tert-butyl(dimethyl)silyl]oxy}-8-hydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C33H55NO5SSi | 详情 | 详情 | |
| (XXIX) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 |
合成路线18
该中间体在本合成路线中的序号：(II)Deoxygenation of epothilone B (I) by means of tungsten hexachloride and butyllithium produced the olefin epothilone D (II). After protection of (II) as the bis-O-silylated derivative (III), cyclopropanation with chloroiodomethane and diethylzinc afforded the cyclopropane adduct (IV). A higher yield procedure to prepare (IV) involved addition of dibromocarbene, generated from bromoform and NaOH under phase-transfer conditions, to olefin (II), followed by reduction of the resulting dibromocyclopropane (V) with azobisisobutyronitrile. Finally, desilylation employing trifluoroacetic acid furnished the title compound.
| 【1】 Fairchild, C.; Kim, S.-H.; Gougoutas, J.; Lee, F.; Long, B.; DiMarco, J.; Vite, G.; Bifano, M.; Tokarski, J.; Johnson, J.; 288555. Drug Data Rep 2000, 22, 8, 686. |
| 【2】 Kim, S.-H.K.; Vite, G.D.; Hofle, G. (Bristol-Myers Squibb Co.); 12,13-Modified epothilone derivs.. WO 9954318; WO 9954319 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 42208 | (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione | C27H41NO6S | 详情 | 详情 | |
| (II) | 40837 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]oxa-13-cyclohexadecene-2,6-dione | C27H41NO5S | 详情 | 详情 | |
| (III) | 42209 | (4S,7R,8S,9S,16S)-5,5,7,9,13-pentamethyl-16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,8-bis[(triethylsilyl)oxy]oxa-13-cyclohexadecene-2,6-dione | C39H69NO5SSi2 | 详情 | 详情 | |
| (IV) | 42210 | (1S,3S,7S,10R,11S,12S,16S)-8,8,10,12,16-pentamethyl-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-7,11-bis[(triethylsilyl)oxy]-4-oxabicyclo[14.1.0]heptadecane-5,9-dione | C40H71NO5SSi2 | 详情 | 详情 | |
| (V) | 42211 | (1S,3S,7S,10R,11S,12S,16R)-17,17-dibromo-8,8,10,12,16-pentamethyl-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-7,11-bis[(triethylsilyl)oxy]-4-oxabicyclo[14.1.0]heptadecane-5,9-dione | C40H69Br2NO5SSi2 | 详情 | 详情 |