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【结 构 式】 
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【分子编号】59413 【品名】(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde 【CA登记号】 |
【 分 子 式 】C19H24O3 【 分 子 量 】300.39776 【元素组成】C 75.97% H 8.05% O 15.98% |
合成路线1
该中间体在本合成路线中的序号：(X)Formylation of estradiol (I) with hexamethylenetetraamine in refluxing trifluoroacetic acid gave the desired 2-formyl estradiol (XI) along with minor amounts of the 4-formyl isomer (X). Diol (XI) was then protected as the bis-benzyl ether (XII) by alkylation with benzyl bromide and NaH under phase-transfer conditions. Baeyer-Villiger oxidation of aldehyde (XII) with m-chloroperbenzoic acid provided phenol (XIII), wich was further alkylated with iodomethane to afford the methyl ether (XIV). The benzyl protecting groups were finally removed by catalytic hydrogenolysis.
| 【2】 Cushman, M.; et al.; Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2-methoxyestradiol, an endogenous mammalian metabolite of estradiol that inhibits tubulin polymerization by binding to the colchicine binding site. J Med Chem 1995, 38, 12, 2041. |
| 【1】 Cushman, H.-M.; He, H.-M.; A versatile synthesis of 2-methoxyestradiol, an endogenous metabolite of estradiol which inhibits tubulin polymerization by binding the colchicine binding site. Bioorg Med Chem Lett 2002, 4, 14, 1725. |
| 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) | 20468 | (8R,9S,13S,14S)-3-hydroxy-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | 53-16-7 | C18H22O2 | 详情 | 详情 |
| (X) | 59413 | (8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde | C19H24O3 | 详情 | 详情 | |
| (XI) | 59414 | (8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-2-carbaldehyde | C19H24O3 | 详情 | 详情 | |
| (XII) | 59415 | (8R,9S,13S,14S,17S)-3,17-bis(benzyloxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-2-carbaldehyde | C33H36O3 | 详情 | 详情 | |
| (XIII) | 59416 | (8R,9S,13S,14S,17S)-3,17-bis(benzyloxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-2-ol | C32H36O3 | 详情 | 详情 | |
| (XIV) | 59417 | benzyl (8R,9S,13S,14S,17S)-17-(benzyloxy)-2-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl ether; (8R,9S,13S,14S,17S)-3,17-bis(benzyloxy)-2-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene | C33H38O3 | 详情 | 详情 |