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【结 构 式】 
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【药物名称】 【化学名称】7alpha-[4-[2-(1-Piperidinyl)ethoxy]benzylsulfanyl]-17alpha-3-oxopregn-4-ene-21,17-carbolactone 【CA登记号】 【 分 子 式 】C36H49NO4S 【 分 子 量 】591.86023 |
【开发单位】Université Laval (Originator) 【药理作用】Pharmacological Tools, 17beta-Hydroxysteroid Dehydrogenase Inhibitors |
合成路线1
Alkylation of 4-hydroxybenzaldehyde (I) with 1-(2-chloroethyl)piperidine hydrochloride (II) in the presence of K2CO3 yielded (piperidinylethoxy)benzaldehyde (III), which was further reduced to the benzylic alcohol (IV) with methanolic NaBH4. Coupling of (IV) with thioacetic acid according to the Mitsunobu procedure yielded thioacetate ester (V), which was converted to the corresponding thiol (VI) by reductive cleavage of the thioester group with LiAlH4.
| 【1】 Leblanc, G.; Noël, P.; Poirier, D.; Labrie, F.; Breton, E.; Luu-The, V.; Tremblay, M.R.; Spironolactone-related inhibitors of type II 17beta-hydroxysteroid dehydrogenase: Chemical synthesis, receptor binding affinities, and proliferative/antiproliferative activities. Bioorg Med Chem 1999, 7, 6, 1013. |
| 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) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
| (II) | 10117 | 1-(2-Chloroethyl)piperidine; N-(2-Chloroethyl)piperidine | 1932-03-2 | C7H14ClN | 详情 | 详情 |
| (III) | 35795 | 4-[2-(1-piperidinyl)ethoxy]benzaldehyde | 26815-04-3 | C14H19NO2 | 详情 | 详情 |
| (IV) | 35796 | [4-[2-(1-piperidinyl)ethoxy]phenyl]methanol | C14H21NO2 | 详情 | 详情 | |
| (V) | 35797 | S-[4-[2-(1-piperidinyl)ethoxy]benzyl] ethanethioate | C16H23NO2S | 详情 | 详情 | |
| (VI) | 35798 | 4-[2-(1-piperidinyl)ethoxy]benzylhydrosulfide; [4-[2-(1-piperidinyl)ethoxy]phenyl]methanethiol | C14H21NOS | 详情 | 详情 |
合成路线2
Elimination of the thioacetyl group of spironolactone (VII) by treatment with NaOMe yielded canrenone (VIII). The title compound was then obtained by 1,6-conjugate addition of thiol (VI) to the dienone (VIII) in the presence of metallic sodium at 60 C.
| 【1】 Leblanc, G.; Noël, P.; Poirier, D.; Labrie, F.; Breton, E.; Luu-The, V.; Tremblay, M.R.; Spironolactone-related inhibitors of type II 17beta-hydroxysteroid dehydrogenase: Chemical synthesis, receptor binding affinities, and proliferative/antiproliferative activities. Bioorg Med Chem 1999, 7, 6, 1013. |