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【结 构 式】 
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【分子编号】42211 【品名】(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 【CA登记号】 |
【 分 子 式 】C40H69Br2NO5SSi2 【 分 子 量 】892.0366 【元素组成】C 53.86% H 7.8% Br 17.91% N 1.57% O 8.97% S 3.59% Si 6.3% |
合成路线1
该中间体在本合成路线中的序号：(V)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 |