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化学学报
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化学学报 ›› 2010, Vol. 68 ›› Issue (22): 2331-2337. 上一篇    下一篇

研究论文

由孕甾-3S,5R,6R,16S,20S-五醇合成黄体酮

季菲1，周涛2，林静容*,1，金荣华1，田伟生*,1,2   

  1. (1上海师范大学资源化学实验室 上海 200234)
    (2中国科学院上海有机化学研究所 上海 200032)
  • 投稿日期:2010-03-31 修回日期:2010-07-31 发布日期:2010-09-08
  • 通讯作者: 林静容 E-mail:jrlin@shnu.edu.cn

Synthesis of Progesterone by First Utilizing Pregnana- 3S,5R,6R,16S,20S-pentaol, a Clean Oxidation Product of Diosgenin

Ji Fei1 Zhou Tao2 Lin Jingrong*,1 Jin Ronghua1 Tian Weisheng*,1,2   

  1. (1 Laboratory of Resource Chemistry, Shanghai Normal University, Shanghai 200234)
    (2 Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032)
  • Received:2010-03-31 Revised:2010-07-31 Published:2010-09-08
  • Contact: LIN JingRong E-mail:jrlin@shnu.edu.cn

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首次利用薯蓣皂甙元降解产物, 孕甾-3S,5R,6R,16S,20S-五醇(3)完成了黄体酮的合成. 孕甾-3S,5R,6R,16S,20S-五醇可方便地通过薯蓣皂甙元经由30%双氧水原地产生的过酸氧化降解得到. 它经过缩酮化反应、乙酰化反应和串联的脱缩酮-溴代乙酰化反应被转化成关键合成中间体16R-溴孕甾-3S,5R,6R,20S-四醇-3,6,20-三乙酸酯(6). 化合物6经锌粉还原、C-3乙酰氧基选择性水解氧化反应和C-5羟基消除反应生成6R,20S-二乙酰氧基孕甾-4-烯-3-酮(10). 化合物10经C-6乙酰氧基还原和C-20乙酰氧基水解-氧化生成目标分子黄体酮. 合成经10步反应, 反应总收率达45.1%.

关键词: 黄体酮, 薯蓣皂甙元, 孕甾-3S,5R,6R,16S,20S-五醇, 资源化学

Progesterone was synthesized by first utilizing pregnane-3S,5R,6R,16S,20S-pentaol (3). Compound 3 can convenient prepared through a clean oxidation degradation reaction of diosgenine with 30% hydrogen perhydoxide in formic acid or acetic acid. It was transformed into a key synthetic intermediate, 16R-bromopregnane-3S,5R,6R,20S-tetraol-3,6,20-triacetate (6) through a sequence of reaction involved ketalization, acetylation and tandem deketalization-bromino-acetylation. Compound 6 subjected to zinc reduction at C-Br and regiodeacetylation-oxidation at C-3 acetate to provide 6R,20S-diacetoxyl-pregn- 4-en-3-one (10). Compound 10 was further converted progesterone through the reduction of C-6 acetate and the deacetylation-oxidation of C-20 acetate. Progesterone was synthesized starting from 3 in 10 steps in 45.1% overall yield.

Key words: progesterone, diosgenin, pregnane-3S,5R,6R,16S,20S-pentaol, resource chemistry