【结 构 式】 |
【分子编号】42569 【品名】(3R)-3-[(3aS,7S,7aR)-3a-methyl-7-[(triethylsilyl)oxy]-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl]-1-butanol 【CA登记号】 |
【 分 子 式 】C20H38O2Si 【 分 子 量 】338.60602 【元素组成】C 70.94% H 11.31% O 9.45% Si 8.29% |
合成路线1
该中间体在本合成路线中的序号:(V)1-Ethylideneperhydroindan-4-ol (I) reacts with Me2AlCl and paraformaldehyde via an ene process to give the homoallylic diol (II), the primary hydroxyl group of which is tosylated by means of TsCl and DMAP and the secondary hydroxyl group silylated by means of TESOTf and lutidine to yield (III). Conversion of (III) into the corresponding nitrile by means of KCN in DMSO, followed by reduction with DIBALH in toluene, affords the aldehyde (IV) (1), which is further reduced in THF by treatment with DIBALH in hexanes to yield (V). The hydroxy silyl ether (V) is then converted into the iodo derivative (VI) by treatment with PPh3, imidazole and I2 in dichloromethane. The iodo silyl ether (VI) reacts with t-BuSH in the presence of DBU in benzene to afford sulfide (VII), which is then oxidized and deprotected with oxone to provide the hydroxy sulfone (VIII). Oxidation of (VIII) with pyridinium dichromate (PDC) in CH2Cl2 gives the keto sulfone (IX), which reacts with the phosphine oxide derivative (X) in THF in the presence of PhLi. Finally, the protecting silyl ether moiety is removed by means of Bu4NF in THF.
【1】 Posner, G.H.; Wang, Q.; Han, G.; et al.; Conceptually new sulfone analogues of the hormone 1alpha,25-dihydroxyvitamin D3: Synthesis and preliminary biological evaluation. J Med Chem 1999, 42, 18, 3425. |
【2】 Posner, G.H.; et al.; Noncalcemic, antiproliferative, transcriptionally active, 24-fluorinated hybrid analogues of the hormone 1alpha,25-dihydroxyvitamin D3. Synthesis and preliminary biological evaluation. J Med Chem 1998, 41, 16, 3008. |
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) | 42566 | (3aR,4S,7aS)-1-[(Z)ethylidene]-7a-methyloctahydro-1H-inden-4-ol | C12H20O | 详情 | 详情 | |
(II) | 38682 | (3aS,7S,7aR)-3-[(1S)-2-hydroxy-1-methylethyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-ol | C13H22O2 | 详情 | 详情 | |
(III) | 42567 | (2S)-2-[(3aS,7S,7aR)-3a-methyl-7-[(triethylsilyl)oxy]-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl]propyl 4-methylbenzenesulfonate | C26H42O4SSi | 详情 | 详情 | |
(IV) | 42568 | (3R)-3-[(3aS,7S,7aR)-3a-methyl-7-[(triethylsilyl)oxy]-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl]butanal | C20H36O2Si | 详情 | 详情 | |
(V) | 42569 | (3R)-3-[(3aS,7S,7aR)-3a-methyl-7-[(triethylsilyl)oxy]-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl]-1-butanol | C20H38O2Si | 详情 | 详情 | |
(VI) | 42570 | ([(3aS,7S,7aR)-3-[(1R)-3-iodo-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-yl]oxy)(triethyl)silane; (3aS,7S,7aR)-3-[(1R)-3-iodo-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-yl triethylsilyl ether | C20H37IOSi | 详情 | 详情 | |
(VII) | 42571 | (3aS,7S,7aR)-3-[(1R)-3-(tert-butylsulfanyl)-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-yl triethylsilyl ether; ([(3aS,7S,7aR)-3-[(1R)-3-(tert-butylsulfanyl)-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-yl]oxy)(triethyl)silane | C24H46OSSi | 详情 | 详情 | |
(VIII) | 42572 | (3aS,7S,7aR)-3-[(1R)-3-(tert-butylsulfonyl)-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-ol | C18H32O3S | 详情 | 详情 | |
(IX) | 42573 | (3aR,7aS)-1-[(1R)-3-(tert-butylsulfonyl)-1-methylpropyl]-7a-methyl-3,3a,5,6,7,7a-hexahydro-4H-inden-4-one | C18H30O3S | 详情 | 详情 | |
(X) | 42574 | [2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl](oxo)diphenylphosphorane; 2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl(diphenyl)phosphine oxide | C33H51O3PSi2 | 详情 | 详情 |