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【结 构 式】 
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【药物名称】 【化学名称】(1S,3S)-3-[4-(Phenoxy)phenylsulfonyl]cyclohexanethiol 【CA登记号】 【 分 子 式 】C18H20O3S2 【 分 子 量 】348.4863 |
【开发单位】Pfizer (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Matrix Metalloproteinase Inhibitors |
合成路线1
Michael addition of 4-(phenoxy)thiophenol (II) to cyclohexenone (I) afforded the ketosulfide (III). This was reduced with NaBH4 to give a diastereomeric mixture of alcohols (IV). Subsequent oxidation of sulfide group of (IV) with Oxone provided sulfone (V). Condensation with potassium thioacetate under Mitsunobu conditions gave the corresponding thioester as a mixture of isomers, from which the major trans isomer (VI) was isolated by chromatography. Finally, deprotection of (VI) with sodium methoxide in MeOH yielded the target thiol.
| 【1】 Mischke, B.V.; Freskos, J.N.; Stevens, A.M.; Mullins, P.B.; McDonald, J.J.; Stegeman, R.A.; Shieh, H.-S.; Synthesis and identification of conformationally constrained selective MMP inhibitors. Bioorg Med Chem Lett 1999, 9, 13, 1757. |
| 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) | 26253 | 2-cyclohexen-1-one；Cyclohex-2-enone；2-cyclohexenone | 930-68-7 | C6H8O | 详情 | 详情 |
| (II) | 26254 | 4-phenoxybenzenethiol; 4-phenoxyphenylhydrosulfide | C12H10OS | 详情 | 详情 | |
| (III) | 26255 | 3-[(4-phenoxyphenyl)sulfanyl]cyclohexanone | C18H18O2S | 详情 | 详情 | |
| (IV) | 26256 | 3-[(4-phenoxyphenyl)sulfanyl]cyclohexanol | C18H20O2S | 详情 | 详情 | |
| (V) | 26257 | 3-[(4-phenoxyphenyl)sulfonyl]cyclohexanol | C18H20O4S | 详情 | 详情 | |
| (VI) | 26258 | S-[(1S,3S)-3-[(4-phenoxyphenyl)sulfonyl]cyclohexyl] ethanethioate | C20H22O4S2 | 详情 | 详情 |