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【结 构 式】 
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【分子编号】55567 【品名】7,11-dihydroxy-3-{2-[2-(hydroxymethyl)-1,3-thiazol-4-yl]-1-methylethenyl}-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione 【CA登记号】 |
【 分 子 式 】C27H41NO7S 【 分 子 量 】523.69108 【元素组成】C 61.93% H 7.89% N 2.67% O 21.39% S 6.12% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of epothilone B (I) with MCPBA in dichloromethane gives the N-oxide (II), which is treated with trifluoroacetic anhydride and 2,6-lutidine in dichloromethane at 70 C in a sealed tube to yield the hydroxymethyl derivative (epothilone F) (III). The reaction of (III) with diphenylphosphoryl azide (DPA) and DBU in THF affords the azidomethyl compound (IV), which is reduced with PMe3 in THF or with H2 and Lindlar catalyst in ethanol to provide the target amino epothilone. Alternatively, the hydroxymethyl derivative (epothilone F) (III) can be obtained by biochemical hydroxylation of epothilone B (I) with Actinomyces sp. strain PTA-XXX.
| 【1】 Kim, S.-H.; Glaser, N.; Leibold, T.; Hoefle, G.; Vite, G. (Bristol-Myers Squibb Co.; Gesellschaft fur Biotechnologische Forschung mbH); C-21 modified epothilones. DE 19907588; EP 1157023; US 6262094; WO 0050423 . |
| 【2】 Matson, J.A.; Lam, K.S.; Huang, X.; Li, W.; McClure, G.A. (Bristol-Myers Squibb Co.); Microbial transformation method for the preparation of an epothilone. WO 0039276 . |
| 【3】 Lee, F.Y. (Bristol-Myers Squibb Co.); Synergistic methods and compsns. for treating cancer. WO 0172721 . |
| 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) | 55566 | 4-{(E)-2-[(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-5,9-dioxo-4,17-dioxabicyclo[14.1.0]heptadec-3-yl]-1-propenyl}-2-methyl-1,3-thiazol-3-ium-3-olate | C27H41NO7S | 详情 | 详情 | |
| (III) | 55567 | 7,11-dihydroxy-3-{2-[2-(hydroxymethyl)-1,3-thiazol-4-yl]-1-methylethenyl}-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione | C27H41NO7S | 详情 | 详情 | |
| (IV) | 55568 | 3-{2-[2-(azidomethyl)-1,3-thiazol-4-yl]-1-methylethenyl}-7,11-dihydroxy-8,8,10,12,16-pentamethyl-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione | C27H40N4O6S | 详情 | 详情 |