Progesterone Synthesis

The rational utilization of resource compounds is one main research field of our group. The one of the most important tasks of our group is exploring the reaction of resource compounds and their application in the synthesis of medicine, agricultural agents and natural product with potential bioactivity in order to realize the rational and high effient utilization of the abundant resource compounds in our country. Based on the research results of our group, my dissertation work is concerned on the synthesis of progesterone first utilizing pregnane-3S, 5R, 6R, 16S, 20S-pentaol, a degradation product of diosgenin..In my Master dissertation, two synthetic routes were designed and explored. In the synthetic route A, pregnane-3S, 5R, 6R, 16S, 20S-pentaol(2) can be 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 (3) through a sequence of reaction involved ketalization, acetylation and tandem deketalization -bromino-acetylation. Compound 3 subjected to zinc reduction at C-Br and regiodeacelylation-oxidation at C-3 acetate to provide (20). Compound 20 was further converted into progesterone through the reduction of C-6 acetate and the deacetylation-oxidation of C-20 acetate. Progesterone was synthesized starting from 2 in 10 steps in 45.1% overall yield.In the synthetic route B, compound 3 was converted into compound 9 through the selective hydrolysis of C-3 acetoxyl group, then oxidation of C-3 hydroxyl group and elimination of C-5 hydroxyl group. Compound 9 subjected to zinc reduction at C-Br and C-6 acetate to give Compound 10. Then followed the deacetylation-oxidation of C-20 acetate, progesterone was obtained in 8 steps in 21% overall yield.