【结 构 式】 |
【分子编号】12549 【品名】(1S,3R,8S,9S,10R,13R,14S,17R)-17-[(1R)-4-Hydroxy-1-methylbutyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol 【CA登记号】 |
【 分 子 式 】C24H40O3 【 分 子 量 】376.5798 【元素组成】C 76.55% H 10.71% O 12.75% |
合成路线1
该中间体在本合成路线中的序号:(XV)3) An alterantive synthesis of the intermediate 26,26,26,27,27,27-hexafluorocholest-5-en-1alpha,3beta,25-triol (VIII) is as follows: The oxidative dehydrogenation of 3beta-hydroxy-5-cholene-24-oic acid methyl ester (XII) with dichlorodicyanobenzoquinone (DDQ) in refluxing dioxane gives 3-oxochola-1,4,6-triene-24-oic acid methyl ester (XIII), which is selectively epoxidized with 30% H2O2 and NaOH in methanol yielding the 1alpha,2alpha-epoxide (XIV). The reductive cleavage of (XIV) with lithium in liquid NH3, followed by hydrolysis with water affords the unsaturated triol (XV), which by selective protection with trityl chloride in pyridine, followed by acetylation with acetic anhydride and dimethylaminopyridine (DMAP) and elimination of the trityl group with p-toluenesulfonic acid, gives 1alpha,3beta-diacetoxy-5-cholen-24-ol (XVI). The reaction of (XVI) with tosyl chloride-pyridine and then with LiBr in DMF yields the 24-bromo derivative (XVII), which is treated with sodium phenylsulfinate in hot DMF affording the sulfone (XVIII). Hydrolysis of the acetoxy groups of (XVIII) with KOH in methanol, followed by silylation of the resulting diol with trimethylsilyl chloride and triethylamine in pyridine gives the silylated sulfone (XIX), which is then condensed with hexafluoroacetone by means of lithium diisopropylamide in THF yielding the sulfonated adduct (XX). Finally, this compound is desilylated to the previously reported triol (VIII) with HCl in methanol.
【1】 Kobayashi, Y.; Taguchi, T.; Mitsuhashi, S.; Eguchi, T.; Ohshima, E.; Ikekawa, N.; Studies on organic fluorine compounds. XXXIX. Studies on steroids. LXXIX. Synthesis of 1alpha,25-dihydroxy-26,26,26,27,27,27-hexafluorovitamin D3. Chem Pharm Bull 1982, 30, 12, 4297-4303. |
【2】 Graul, A.; Castaner, J.; Falecalcitriol. Drugs Fut 1997, 22, 5, 473. |
【3】 Hata, G.; Mutoh, M.; Hashimoto, H. (Toray Industries, Inc.); Novel platinum(II) complex and drug for treating malignant tumor. EP 0457921; JP 1991500696; US 5302587; WO 9109041 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VIII) | 12542 | (1S,3R,8S,9S,10R,13R,14S,17R)-10,13-Dimethyl-17-[(1R)-6,6,6-trifluoro-5-hydroxy-1-methyl-5-(trifluoromethyl)hexyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol | C27H40F6O3 | 详情 | 详情 | |
(XII) | 12546 | methyl (4R)-4-[(3S,8S,9S,10R,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate; 3beta-Hydroxichol-5-en-24-oic acid methyl ester | 20231-57-6 | C25H40O3 | 详情 | 详情 |
(XIII) | 12547 | methyl (4R)-4-[(8S,9S,10S,13R,14S,17R)-10,13-dimethyl-3-oxo-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-17-yl]pentanoate | C25H34O3 | 详情 | 详情 | |
(XIV) | 12548 | methyl (4R)-4-[(2aR,3aR,3bR,3cS,5aR,6R,8aS,8bS)-3b,5a-dimethyl-2-oxo-2a,3a,3b,3c,4,5,5a,6,7,8,8a,8b-dodecahydro-2H-cyclopenta[7,8]phenanthro[3,4-b]oxiren-6-yl]pentanoate | C25H34O4 | 详情 | 详情 | |
(XV) | 12549 | (1S,3R,8S,9S,10R,13R,14S,17R)-17-[(1R)-4-Hydroxy-1-methylbutyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol | C24H40O3 | 详情 | 详情 | |
(XVI) | 12550 | (1S,3R,8S,9S,10R,13R,14S,17R)-1-(acetoxy)-17-[(1R)-4-hydroxy-1-methylbutyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C28H44O5 | 详情 | 详情 | |
(XVII) | 12551 | (1S,3R,8S,9S,10R,13R,14S,17R)-1-(acetoxy)-17-[(1R)-4-bromo-1-methylbutyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C28H43BrO4 | 详情 | 详情 | |
(XVIII) | 12552 | (1S,3R,8S,9S,10R,13R,14S,17R)-1-(acetoxy)-10,13-dimethyl-17-[(1R)-1-methyl-4-(phenylsulfonyl)butyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C34H48O6S | 详情 | 详情 | |
(XIX) | 12553 | (4R)-4-[(1S,3S,8S,9S,10S,13R,14S,17R)-10,13-Dimethyl-1,3-bis[(trimethylsilyl)methyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentyl phenyl sulfone; ([(1S,3S,8S,9S,10S,13R,14S,17R)-10,13-Dimethyl-17-[(1R)-1-methyl-4-(phenylsulfonyl)butyl]-3-[(trimethylsilyl)methyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-1-yl]methyl)(trimethyl)silane | C38H64O2SSi2 | 详情 | 详情 | |
(XX) | 12554 | (6R)-6-[(1S,3S,8S,9S,10S,13R,14S,17R)-10,13-Dimethyl-1,3-bis[(trimethylsilyl)methyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1,1,1-trifluoro-3-(phenylsulfonyl)-2-(trifluoromethyl)-2-heptanol | C41H64F6O3SSi2 | 详情 | 详情 |