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【结 构 式】 
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【分子编号】11055 【品名】(2S,3S,4R,5R,6R)-3-(acetoxy)-6-hydroxy-5-iodo-2-methyltetrahydro-2H-pyran-4-yl acetate 【CA登记号】 |
【 分 子 式 】C10H15IO6 【 分 子 量 】358.12997 【元素组成】C 33.54% H 4.22% I 35.44% O 26.8% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reaction of racemic 4-demethoxydaunomycinone (I) with Br2 followed by hydrolysis in basic medium gives 4-demethoxyadriamycinone (II), which is treated with tert-butyldimethylsilyl chloride and imidazole in DMF to yield the monoprotected compound (III). The condensation of (III) with 3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-mannopyranose (IV) by means of N-iodosuccinimide (NIS), followed by chromatographic separation of the diastereomers affords (7S,9S)-14-O-(tert-butyldimethylsilyl)-4-demethoxy-7-O-(3,4-di-O-acetyl-2,6-dideoxy-2-iodo-alpha-L-mannopyranosyl)adriamycinone (V). The hydrolysis of (V) with sodium methoxide in methanol gives the silylated compound (VI), which is finally desilylated with tetrabutylammonium fluoride (TBAF) in dichloromethane/THF/pyridine.
| 【1】 Graul, A.; Prous, J.; Castaner, J.; Annamycin. Drugs Fut 1997, 22, 9, 948. |
| 【2】 Horton, D.; Priebe, W. (Ohio State University); 4-Demethoxy-3'-desamino-2'-haloanthracycline and pharmaceutical compsn. US 4537882 . |
| 【3】 Horton, D.; Priebe, W.; Varela, O.; Synthesis of antitumor-active (7S,9S)-4-demethoxy-7-O-(2,6-dideoxy-2-iodo-alpha-L-mannopyranosyl) adriamycinone: Preparative resolution of a racemic anthracyclinone by alkoxyhalogenation of a glycal. Carbohydr Res 1984, 130, C1-3. |
| 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) | 11052 | (9S)-9-Acetyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C20H16O7 | 详情 | 详情 | |
| (II) | 11053 | (9S)-9-Glycoloyl-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C20H16O8 | 详情 | 详情 | |
| (III) | 11054 | (9S)-9-(2-[[tert-Butyl(dimethyl)silyl]oxy]acetyl)-6,7,9,11-tetrahydroxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C26H30O8Si | 详情 | 详情 | |
| (IV) | 11055 | (2S,3S,4R,5R,6R)-3-(acetoxy)-6-hydroxy-5-iodo-2-methyltetrahydro-2H-pyran-4-yl acetate | C10H15IO6 | 详情 | 详情 | |
| (V) | 11056 | (2S,3S,4R,5R,6R)-3-(acetoxy)-6-[[(1S,3S)-3-(2-[[tert-butyl(dimethyl)silyl]oxy]acetyl)-3,5,12-trihydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy]-5-iodo-2-methyltetrahydro-2H-pyran-4-yl acetate | C36H43IO13Si | 详情 | 详情 | |
| (VI) | 11057 | (7S,9S)-9-(2-[[tert-Butyl(dimethyl)silyl]oxy]acetyl)-7-[[(2R,3R,4R,5R,6S)-4,5-dihydroxy-3-iodo-6-methyltetrahydro-2H-pyran-2-yl]oxy]-6,9,11-trihydroxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C32H39IO11Si | 详情 | 详情 |