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【结 构 式】 
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【分子编号】57129 【品名】(6R)-6-((1R,7aR)-4-{(E,2R)-2-methoxy-2-[(5R)-2-methylenebicyclo[3.1.0]hex-1-yl]ethylidene}-7a-methyloctahydro-1H-inden-1-yl)-2-methyl-2-heptanol 【CA登记号】 |
【 分 子 式 】C28H46O2 【 分 子 量 】414.67204 【元素组成】C 81.1% H 11.18% O 7.72% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of vitamin D3 (I) with Ts-Cl in pyridine gives the tosylate (II), which is treated with NaHCO3 in hot methanol to yield 3,5-cyclovitamin D3 (III). The oxidation of (III) with SeO2 and tBu-OOH in dichloromethane, followed by acetylation affords 1-alpha-acetoxy-25-hydroxy-3,5-cyclovitamin D3 (IV). The dihydroxylation of the exo-double bond of (IV) with OsO4 in pyridine affords the alpha diol (V), which is oxidized with NaIO4 in methanol to provide the oxo cyclovitamin (VI). The reduction of (VI) with NaBH4 in ethanol gives the secondary alcohol (VII), which is mesylated with Ms-Cl and TEA in dichloromethane to yield the mesylate (VIII). The crude (VIII) is treated with LiAlH4 in THF to afford 1-alpha,25-dihydroxy-3,5-cyclovitamin D3 (IX). The cycloreversion of (IX) by means of hot acetic acid provides a mixture of the two monoacetylated vitamins (X) and (XI), which, without separation is hydrolyzed with KOH in methanol/ethyl ether to give the target 1-alpha,25-dihydroxy-19-nor-vitamin D3.
| 【1】 Paaren, H.E.; et al.; Direct C(1) hydroxylation of vitamin D3 and related compounds. J Org Chem 1980, 45, 16, 3253. |
| 【2】 DeLuca, H.F.; Schnoes, H.K.; Perlman, K.L.; Sicinski, R.R.; Prahl, J.M. (Wisconsin Alumni Research Foundation); 19-Nor vitamin D cpds. EP 0387077; JP 1991505330; US 5246925; WO 9010620 . |
| 【3】 Perlman, K.L.; et al.; 1alpha,25-Dihydroxy-19-nor-vitamin D3, a novel vitamin D-related compound with potential therapeutic activity. Tetrahedron Lett 1990, 31, 13, 1823. |
| 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) | 57127 | (1S)-3-((Z)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}ethylidene)-4-methylenecyclohexanol | C27H44O2 | 详情 | 详情 | |
| (II) | 57128 | (1S)-3-((Z)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}ethylidene)-4-methylenecyclohexyl 4-methylbenzenesulfonate | C34H50O4S | 详情 | 详情 | |
| (III) | 57129 | (6R)-6-((1R,7aR)-4-{(E,2R)-2-methoxy-2-[(5R)-2-methylenebicyclo[3.1.0]hex-1-yl]ethylidene}-7a-methyloctahydro-1H-inden-1-yl)-2-methyl-2-heptanol | C28H46O2 | 详情 | 详情 | |
| (IV) | 57130 | (1R,3S,5S)-1-((1R)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}-1-methoxyethyl)-2-methylenebicyclo[3.1.0]hex-3-yl acetate | C30H48O4 | 详情 | 详情 | |
| (V) | 57131 | (1S,3S,5S)-1-((1R)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}-1-methoxyethyl)-2-hydroxy-2-(hydroxymethyl)bicyclo[3.1.0]hex-3-yl acetate | C30H50O6 | 详情 | 详情 | |
| (VI) | 57132 | (1S,3S,5S)-1-((1R)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}-1-methoxyethyl)-2-oxobicyclo[3.1.0]hex-3-yl acetate | C29H46O5 | 详情 | 详情 | |
| (VII) | 57133 | (1R,3S,5S)-1-((1R)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}-1-methoxyethyl)-2-hydroxybicyclo[3.1.0]hex-3-yl acetate | C29H48O5 | 详情 | 详情 | |
| (VIII) | 57134 | (1S,3S,5S)-1-((1R)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}-1-methoxyethyl)-2-[(methylsulfonyl)oxy]bicyclo[3.1.0]hex-3-yl acetate | C30H50O7S | 详情 | 详情 | |
| (IX) | 57135 | (1S,3S,5S)-1-((1R)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}-1-methoxyethyl)bicyclo[3.1.0]hexan-3-ol | C27H46O3 | 详情 | 详情 | |
| (X) | 57136 | (1R,5R)-3-((E)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}ethylidene)-5-hydroxycyclohexyl acetate | C28H46O4 | 详情 | 详情 | |
| (XI) | 57137 | (1R,5R)-3-((Z)-2-{(1R,7aR)-1-[(1R)-5-hydroxy-1,5-dimethylhexyl]-7a-methyloctahydro-4H-inden-4-ylidene}ethylidene)-5-hydroxycyclohexyl acetate | C28H46O4 | 详情 | 详情 |