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【结 构 式】 
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【分子编号】11733 【品名】(1S,3R,9S,10R,13S,14S,17S)-17-[(1S)-1-(3-Hydroxy-3-methylbutoxy)ethyl]-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol 【CA登记号】 |
【 分 子 式 】C26H42O4 【 分 子 量 】418.61708 【元素组成】C 74.6% H 10.11% O 15.29% |
合成路线1
该中间体在本合成路线中的序号：(XXI)5) The acetylation of 20(S)-(3-hydroxy-3-methylbutoxy)pregna-5,7-diene-1alpha,3beta-diol (XXI) with acetic anhydride and dimethylaminopyridine (DMAP) in pyridine gives the 1alpha,3beta-diacetoxy derivative (XXII), which was submitted to UV irradiation with a 400 W high-pressure mercury lamp in THF yielding the corresponding 22-oxavitamin D3 derivative (XXIII). Finally, this compound is deacetylated by a treatment with KOH in methanol.
| 【1】 Leeson, P.A.; Martel, A.M.; Castaner, J.; 22-Oxacalcitriol. Drugs Fut 1996, 21, 12, 1229. |
| 【2】 Mikami, T. (Chugai Pharmaceutical Co. Ltd.); Vitamin D deriv. and process for producing the same. WO 9408958 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXI) | 11733 | (1S,3R,9S,10R,13S,14S,17S)-17-[(1S)-1-(3-Hydroxy-3-methylbutoxy)ethyl]-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol | C26H42O4 | 详情 | 详情 | |
| (XXII) | 11734 | (1S,3R,9S,10R,13S,14S,17S)-1-(acetoxy)-17-[(1S)-1-(3-hydroxy-3-methylbutoxy)ethyl]-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C30H46O6 | 详情 | 详情 | |
| (XXIII) | 11735 | (1R,5S)-3-((Z)-2-[(1S,3aS,7aS)-1-[(1S)-1-(3-hydroxy-3-methylbutoxy)ethyl]-7a-methyloctahydro-4H-inden-4-ylidene]ethylidene)-5-(acetoxy)-4-methylenecyclohexyl acetate | C30H46O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXV)The synthesis of 22-oxacalcitriol labeled with tritium at the 26-methyl group has been performed as follows: The starting compound is the previously obtained 3-oxobutoxy derivative (X), which is submitted to a Grignard alkylation with 3CH3MgI giving the labeled 3-hydroxy-3-methylbutoxy derivative (XXIV). The deprotection of (XXIV) with tetrabutylammonium fluoride affords the triol derivative (XXV), which is finally irradiated with a 400 W high-pressure mercury lamp with a Vycor filter.
| 【1】 Leeson, P.A.; Martel, A.M.; Castaner, J.; 22-Oxacalcitriol. Drugs Fut 1996, 21, 12, 1229. |
| 【2】 Watanabe, H.; Akiyama, M.; Kawanishi, T.; Kubodera, N.; Synthesis of tritiated 1alpha,25-dihydroxy-22-oxavitamin D3. J Label Compd Radiopharm 1995, 36, 7, 645-54. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 11722 | 4-[[(1S)-1-((1S,3R,9S,10R,13S,14S,17S)-1,3-Bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethyl]oxy]-2-butanone | C37H66O4Si2 | 详情 | 详情 | |
| (XXIV) | 11723 | 4-[[(1S)-1-((1S,3R,9S,10R,13S,14S,17S)-1,3-Bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethyl]oxy]-2-methyl-2-butanol | C38H70O4Si2 | 详情 | 详情 | |
| (XXIV) | 45069 | 4-[[(1S)-1-((1S,3R,9S,10R,13S,14S,17S)-1,3-bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethyl]oxy]-2-methyl-2-butanol | C38H70O4Si2 | 详情 | 详情 | |
| (XXV) | 11733 | (1S,3R,9S,10R,13S,14S,17S)-17-[(1S)-1-(3-Hydroxy-3-methylbutoxy)ethyl]-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-1,3-diol | C26H42O4 | 详情 | 详情 | |
| (XXV) | 45070 | 4-[((1S)-1-[(1S,3aS,7aS)-4-[(E)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]ethyl)oxy]-2-methyl-2-butanol | C38H70O4Si2 | 详情 | 详情 |