非那雄胺的合成研究

 目的 研究非那雄胺的合成工艺。方法 以孕烯醇酮为原料制得3-羰基-4-雄甾烯-17β-羰酸，用高锰酸钾和高碘酸钠打开A环，然后与氨反应闭环，再经Pd/C催化氢化制得4-氮杂-5α甾体化合物，然后17β-羰酸成酯，DDQ脱去1，2-氢，最后与叔丁胺的格氏试剂反应制得非那雄胺。结果 非那雄胺及其各中间体经红外、核磁、质谱证实。结论 本法无需使用昂贵的PtO₂，苯亚硒酸酐和2，2′-二吡啶二硫化物（DPDS）等试剂，总收率高，而且不需柱色谱纯化，是理想的工业化生产路线。

Studies on synthesis of finasteride

OBJECTIVE To study the synthesis of finasteride METHODS The ring A of 3-oxo-4-androstene-17β-carboxylic acid was opened with KMnO₄-NaIO₄. Then the product compound reacted with NH₃ and hydrogenated with Pd/C to get 3-oxo-4-aza-5α-androsta-17β-carboxylic acid, which was esterified with anhydrous CH₃OH, dehydrogenated with DDQ/BSTFA, and reacted with t-butylamino magnesium bromide to get finasteride RESULTS The structures of all the intermediates and finasteride were verified by IR, 1HNMR and MS CONCLUSION This method was successful without using those expensive reagents such as PtO₂, (PhSeO)₂O and 2,2′-dipyridyl disulphide. The column chromatography was not necessary for all steps. The yield of finasteride is much higher than reported yield.