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【结 构 式】 
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【药物名称】KH-1266 【化学名称】(5Z,7E)-17beta-[2(R)-(4-Ethyl-4-hydroxyhexyloxy)-1(R)-methylbutyl]-9,10-secoandrosta-5,7,10(19)-trien-1alpha,3beta-diol 【CA登记号】 【 分 子 式 】C32H54O4 【 分 子 量 】502.78478 |
【开发单位】Leo (Originator) 【药理作用】ONCOLYTIC DRUGS, Vitamin D Analogs |
合成路线1
Vitamin D derivative (I) was condensed with ethyllithium al low temperature to give, after chromatographic separation of isomers, alcohol (II). Alkylation of (II) with 6-bromo-3-ethyl-3-(trimethylsilyloxy)hexane (III) and potassium tert-butoxide in the presence of a crown ether afforded ether (IV), which was then photochemically isomerized in the presence of anthracene as a sensitizer to give (V). Final deprotection of silyl groups of (V) with 5% hydrogen fluoride in ethyl acetate-acetonitrile yielded the title compound.
| 【1】 Calverley, M.J.; Grue-Sorensen, G.; Binderup, E.T. (Leo Pharmaceutical Products Ltd. A/S); Novel vitamin D analogues. EP 0522013; JP 1993505613; US 5374629; WO 9115475 . |
| 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) | 27521 | (2R)-2-[(1R,3aS,7aR)-4-[(E)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]propanal | C34H60O3Si2 | 详情 | 详情 | |
| (II) | 27526 | (2R,3R)-2-[(1R,3aS,7aR)-4-[(E)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]-3-pentanol | C36H66O3Si2 | 详情 | 详情 | |
| (III) | 14241 | (5-Bromo-2,2-diethylpentyl)(trimethyl)silane | C12H27BrSi | 详情 | 详情 | |
| (IV) | 27527 | [5-[((1R,2R)-2-[(1R,3aS,7aR)-4-[(E)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-ethylpropyl)oxy]-2,2-diethylpentyl](trimethyl)silane | C48H92O3Si3 | 详情 | 详情 | |
| (V) | 27528 | (1R,2R)-2-[(1R,3aS,7aR)-4-[(Z)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-ethylpropyl 4-ethyl-4-[(trimethylsilyl)methyl]hexyl ether | C48H92O3Si3 | 详情 | 详情 |