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【结 构 式】 
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【分子编号】62177 【品名】(1S,2Z)-4-[((2R,3R,5S,6S)-6-{(2E,4E)-5-[(2R,3S,6S)-3-(acetyloxy)-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl]-3-methyl-2,4-pentadienyl}-2,5-dimethyltetrahydro-2H-pyran-3-yl)amino]-1-methyl-4-oxo-2-butenyl acetate 【CA登记号】 |
【 分 子 式 】C30H45NO8 【 分 子 量 】547.68924 【元素组成】C 65.79% H 8.28% N 2.56% O 23.37% |
合成路线1
该中间体在本合成路线中的序号：(XLI)Condensation of sulfone (XXI) with aldehyde (XXXVII), followed by treatment with benzoyl chloride affords adduct (XXXVIII). Reductive elimination of sulfone (XXXVIIII) with sodium amalgam leads to the conjugated diene (XXXIX). Both O-silyl groups of (XXXIX) are removed by treatment with tetrabutylammonium fluoride, providing diol (XL). Then, esterification of (XL) with acetic anhydride and DMAP furnishes diacetate (XLI).
| 【1】 Horigome, M.; Motoyoshi, H.; Watanabe, H.; Kitahara, T.; A synthesis of FR901464. Tetrahedron Lett 2001, 42, 46, 8207. |
| 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) | 62158 | (Z,4S)-4-{[tert-butyl(diphenyl)silyl]oxy}-N-((2R,3R,5S,6S)-2,5-dimethyl-6-{(E)-3-methyl-4-[(4-methylphenyl)sulfonyl]-2-butenyl}tetrahydro-2H-pyran-3-yl)-2-pentenamide | C40H53NO5SSi | 详情 | 详情 | |
| (XXVII) | 62173 | (2S,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-carbaldehyde | C15H28O4Si | 详情 | 详情 | |
| (XXXVIII) | 62174 | (1S,3E)-1-((2R,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl)-5-{(2S,3S,5R,6R)-5-[((Z,4S)-4-{[tert-butyl(diphenyl)silyl]oxy}-2-pentenoyl)amino]-3,6-dimethyltetrahydro-2H-pyran-2-yl}-3-methyl-2-[(4-methylphenyl)sulfonyl]-3-pentenyl benzoate | C62H85NO10SSi2 | 详情 | 详情 | |
| (XXXIX) | 62175 | (Z,4S)-N-{(2R,3R,5S,6S)-6-[(2E,4E)-5-((2R,3S,6S)-3-{[tert-butyl(dimethyl)silyl]oxy}-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl)-3-methyl-2,4-pentadienyl]-2,5-dimethyltetrahydro-2H-pyran-3-yl}-4-{[tert-butyl(diphenyl)silyl]oxy}-2-pentenam | C48H73NO6Si2 | 详情 | 详情 | |
| (XL) | 62176 | (Z,4S)-4-hydroxy-N-((2R,3R,5S,6S)-6-{(2E,4E)-5-[(2R,3S,6S)-3-hydroxy-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl]-3-methyl-2,4-pentadienyl}-2,5-dimethyltetrahydro-2H-pyran-3-yl)-2-pentenamide | C26H41NO6 | 详情 | 详情 | |
| (XLI) | 62177 | (1S,2Z)-4-[((2R,3R,5S,6S)-6-{(2E,4E)-5-[(2R,3S,6S)-3-(acetyloxy)-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl]-3-methyl-2,4-pentadienyl}-2,5-dimethyltetrahydro-2H-pyran-3-yl)amino]-1-methyl-4-oxo-2-butenyl acetate | C30H45NO8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XLI)Treatment of diester (XLI) with LiOH produces a mixture of hydrolyzed products, from which the desired mono-acetylated compound (XLII) can be separated from its mono-acetyl regiosiomer and the fully hydrolyzed product. Epoxidation of the exocyclic olefin (XLII) with m-CPBA furnishes diastereoselectively epoxide (XLIII). Finally, deacetylation of the methyl ketal (XLIII) to the target hemiketal compound is achieved by treatment with an acidic cation-exchange resin in wet THF.
| 【1】 Horigome, M.; Motoyoshi, H.; Watanabe, H.; Kitahara, T.; A synthesis of FR901464. Tetrahedron Lett 2001, 42, 46, 8207. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLI) | 62177 | (1S,2Z)-4-[((2R,3R,5S,6S)-6-{(2E,4E)-5-[(2R,3S,6S)-3-(acetyloxy)-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl]-3-methyl-2,4-pentadienyl}-2,5-dimethyltetrahydro-2H-pyran-3-yl)amino]-1-methyl-4-oxo-2-butenyl acetate | C30H45NO8 | 详情 | 详情 | |
| (XLII) | 62178 | (1S,2Z)-4-[((2R,3R,5S,6S)-6-{(2E,4E)-5-[(2R,3S,6S)-3-hydroxy-6-methoxy-6-methyl-4-methylenetetrahydro-2H-pyran-2-yl]-3-methyl-2,4-pentadienyl}-2,5-dimethyltetrahydro-2H-pyran-3-yl)amino]-1-methyl-4-oxo-2-butenyl acetate | C28H43NO7 | 详情 | 详情 | |
| (XLIII) | 62179 | (1S,2Z)-4-[((2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-4-hydroxy-7-methoxy-7-methyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadienyl}-2,5-dimethyltetrahydro-2H-pyran-3-yl)amino]-1-methyl-4-oxo-2-butenyl acetate | C28H43NO8 | 详情 | 详情 |