由孕甾-3S,5R,6R,16S,20S-五醇合成黄体酮

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

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%.

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.