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【结 构 式】 
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【分子编号】42519 【品名】(2S,4aR,4bS,6aS,7S,7aS,8aS,8bR,8cR)-7-(3,3-dimethoxypropyl)-4a,6a-dimethyl-1,2,3,4,4a,4b,5,6,6a,7,7a,8,8a,8b,8c,9-hexadecahydrocyclopropa[4,5]cyclopenta[1,2-a]phenanthrene-2,7-diol 【CA登记号】 |
【 分 子 式 】C25H40O4 【 分 子 量 】404.5902 【元素组成】C 74.22% H 9.97% O 15.82% |
合成路线1
该中间体在本合成路线中的序号：(XIV)3) Reaction of 3beta-hydroxy-15beta,16beta-methylene-5-androsten-17-one (I) with 1-bromo-3,3-dimethoxypropane (XIII) and lithium in THF gives the 17alpha-(3,3-dimethoxypropyl) derivative (XIV), which by treatment with 70% acetic acid provides the spiro compound (XV). Oxidation of compound (XV) with cyclohexanone in the presence of (i-PrO)3Al and then treatment with 2N H2SO4 affords 15beta,16beta-methylene-3-oxo-17alpha-pregn-4-ene-21,17-carbolactone (XVI). Treatment of (XVI) with chloranil in t-BuOH yields the pregnadiene carbolactone (XVII), which is finally reacted with trimethylsulfoxonium iodide (XVIII) and NaH in DMSO.
| 【1】 Norman, P.; Castaner, R.M.; Castaner, J.; Drospirenone. Drugs Fut 2000, 25, 12, 1247. |
| 【2】 Losert, W.; Bittler, D.; Vasals-Stenzel, J.; Wiechert, R.; Kerb, U. (Schering AG); Novel spironolactones and process for their preparation. DE 2652761; US 4129564 . |
| 【3】 Nickisch, K.; Wiechert, R.; Laurent, H.; Petzoldt, K.; Bittler, D. (Schering AG); Process for preparing 3beta,7beta-dihydroxy-DELTA5-steroids. DE 3042136; EP 0051143; JP 1982122798; US 4416985; US 4614616 . |
| 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) | 42507 | (2S,4aR,4bS,6aS,7aS,8aS,8bR,8cR)-2-hydroxy-4a,6a-dimethyl-2,3,4,4a,4b,5,6,6a,7a,8,8a,8b,8c,9-tetradecahydrocyclopropa[4,5]cyclopenta[1,2-a]phenanthren-7(1H)-one | C20H28O2 | 详情 | 详情 | |
| (XIII) | 29689 | 3-bromo-1,1-dimethoxypropane; 3-bromo-1-methoxypropyl methyl ether | 36255-44-4 | C5H11BrO2 | 详情 | 详情 |
| (XIV) | 42519 | (2S,4aR,4bS,6aS,7S,7aS,8aS,8bR,8cR)-7-(3,3-dimethoxypropyl)-4a,6a-dimethyl-1,2,3,4,4a,4b,5,6,6a,7,7a,8,8a,8b,8c,9-hexadecahydrocyclopropa[4,5]cyclopenta[1,2-a]phenanthrene-2,7-diol | C25H40O4 | 详情 | 详情 | |
| (XV) | 42520 | C23H34O3 | 详情 | 详情 | ||
| (XVI) | 29692 | 3-Oxo-cyclopropa[1',2':15-beta,16-beta]pregn-4-ene-21,17-carbolactone | C23H30O3 | 详情 | 详情 | |
| (XVII) | 11776 | 3-Oxo-cyclopropa[1',2':15-beta,16-beta]pregan-4,6-diene-21,17-carbolactone | C23H28O3 | 详情 | 详情 | |
| (XVIII) | 29693 | Trimethylsulfoxonium iodide | 1774-47-6 | C3H9IOS | 详情 | 详情 |