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【结 构 式】 
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【分子编号】34579 【品名】(10S,13R,14S,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one 【CA登记号】 |
【 分 子 式 】C28H40O 【 分 子 量 】392.625 【元素组成】C 85.66% H 10.27% O 4.07% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of ergosta-4,6,22-trien-3-one (I) with DDQ and 5-sulfosalicylic acid in refluxing dioxane gives ergosta-1,4,6,22-tetraen-3-one (II), which is acylated with isopropenyl acetate and Ts-OH in refluxing butyl acetate yielding 3-acetoxyergosta-1,3,5,7,22-pentaene (III). The reduction of (III) with calcium borohydridde in ethanol affords ergosta-1,5,7,22-tetraen-3beta-ol (IV), which is condensed with 4-phenyl-3H-4,5-dihydro-1,2,4-triazole-3,5-dione (V) in ethyl acetate yielding the Diels-Alder adduct (VI). The silylation of (VI) with TBDMS-Cl and imidazole affords the silyl ether (VII), which is epoxidized with MCPBA in chloroform giving the 1alpha,2alpha-22,23-diepoxide (VIII). The elimination of the silyl group with TBAF in THF gives the 3beta-alcohol (IX).
| 【1】 Tachibana, Y.; A convenient syntesis of a 1alpha-hydroxyvitamin D2. Bull Chem Soc Jpn 1988, 61, 11, 3915. |
| 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) | 34578 | (10R,13R,14S,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-1,2,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C28H42O | 详情 | 详情 | |
| (II) | 34579 | (10S,13R,14S,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one | C28H40O | 详情 | 详情 | |
| (III) | 34580 | (10R,13R,14R,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-10,11,12,13,14,15,16,17-octahydro-9H-cyclopenta[a]phenanthren-3-yl acetate | C30H42O2 | 详情 | 详情 | |
| (IV) | 34581 | (3R,10R,13R,14R,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-4,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-ol | C28H42O | 详情 | 详情 | |
| (V) | 11749 | 4-Phenyl-3H-1,2,4-triazole-3,5(4H)-dione; 4-Phenyl-1,2,4-triazoline-3,5-dione | 4233-33-4 | C8H5N3O2 | 详情 | 详情 |
| (VI) | 34582 | (1S,2R,5R,6R,10R,13R,15S)-13-hydroxy-6,10-dimethyl-18-phenyl-5-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-16,18,20-triazahexacyclo[13.5.2.0(1,9).0(2,6).0(10,15).0(16,20)]docosa-11,21-diene-17,19-dione | C36H47N3O3 | 详情 | 详情 | |
| (VII) | 34583 | (1S,2R,5R,6R,10R,13R,15S)-13-[[tert-butyl(dimethyl)silyl]oxy]-6,10-dimethyl-18-phenyl-5-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-16,18,20-triazahexacyclo[13.5.2.0(1,9).0(2,6).0(10,15).0(16,20)]docosa-11,21-diene-17,19-dione | C42H61N3O3Si | 详情 | 详情 | |
| (VIII) | 34584 | (1S,2R,5R,6R,10R,11R,13R,14R,16S)-14-[[tert-butyl(dimethyl)silyl]oxy]-5-((1S)-1-[3-[(1R)-1,2-dimethylpropyl]-2-oxiranyl]ethyl)-6,10-dimethyl-19-phenyl-12-oxa-17,19,21-triazaheptacyclo[14.5.2.0(1,9).0(2,6).0(10,16).0(11,13).0(17,21)]tricos-22-ene-18, | C42H61N3O5Si | 详情 | 详情 | |
| (IX) | 34585 | (1S,2R,5R,6R,10R,11R,13S,14R,16S)-5-((1S)-1-[3-[(1R)-1,2-dimethylpropyl]-2-oxiranyl]ethyl)-14-hydroxy-6,10-dimethyl-19-phenyl-12-oxa-17,19,21-triazaheptacyclo[14.5.2.0(1,9).0(2,6).0(10,16).0(11,13).0(17,21)]tricos-22-ene-18,20-dione | C36H47N3O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The Oppenauer oxidation of ergosterol (XIX) gives ergosta-4,6,22-trien-3-one (I), which is dehydrogenated with SeO2 to ergosta-1,4,6,22-tetraen-3-one (II). The epoxidation of (II) with H2O2 and NaOH in dioxane affords the 1alpha,2alpha-epoxide (XX), which is reduced with Li in liquid NH3 to give ergost-5-ene-1alpha,3beta-diol (XXI). The acylation of (XXI) with acetic anhydride and pyridine yields the diacetate (XXII), which is dehydrogenated by the bromination dehydrobromination method to provide the previously reported 1alpha-acetoxyergosteryl acetate (XII). The UV irradiation of (XII) with a high pressure Hg lamp gives the 1alpha-hydroxyvitamin D2 diacetate (XIII), which is finally, deacylated with KOH in methanol.
| 【1】 Lam, H.Y.; et al.; Synthesis of 1alpha-hydroxyergocalciferol. Steroids 1977, 30, 5, 671. |
| 【2】 Schnoes, H.K.; DeLuca, H.F.; Lam, H.-Y. (Wisconsin Alumni Research Foundation); 1alpha-Hydroxyergocalciferol and processes for preparing same. US 3907843 . |
| 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) | 34578 | (10R,13R,14S,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-1,2,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C28H42O | 详情 | 详情 | |
| (II) | 34579 | (10S,13R,14S,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-8,9,10,11,12,13,14,15,16,17-decahydro-3H-cyclopenta[a]phenanthren-3-one | C28H40O | 详情 | 详情 | |
| (XII) | 34588 | (1S,3R,10R,13R,14R,17R)-1-(acetoxy)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C32H48O4 | 详情 | 详情 | |
| (XIII) | 34589 | (1R,5S)-3-((Z)-2-[(1R,3aR,7aR)-7a-methyl-1-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]octahydro-4H-inden-4-ylidene]ethylidene)-5-(acetoxy)-4-methylenecyclohexyl acetate | C32H48O4 | 详情 | 详情 | |
| (XIX) | 34595 | (3S,10R,13R,14R,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol | 57-87-4 | C28H44O | 详情 | 详情 |
| (XX) | 34596 | (2aR,3aR,3bR,5aR,6R,8aS)-3b,5a-dimethyl-6-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-2a,3a,3b,3c,4,5,5a,6,7,8,8a,8b-dodecahydro-2H-cyclopenta[7,8]phenanthro[3,4-b]oxiren-2-one | C28H40O2 | 详情 | 详情 | |
| (XXI) | 34597 | (1S,3R,10R,13R,14S,17R)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol | C28H46O2 | 详情 | 详情 | |
| (XXII) | 34598 | (1S,3R,10R,13R,14S,17R)-1-(acetoxy)-10,13-dimethyl-17-[(1R,2E,4R)-1,4,5-trimethyl-2-hexenyl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C32H50O4 | 详情 | 详情 |