Partial Promise Diosgenin Synthesis Study

Pennogenin is the main bioactive components of Chonglou, one of Chinese traditional medicine, and its good medicinal value and the scarcity of resource has attracted the organic chemist's attention. The rational utilization of resource compounds is one main research field of our group. Based on the research results of rational utilization of the abundant steroidal sapogenins, my dissertation is concerned on the synthesis of the pennogenin by utilizing the intact skeleton of diosgenin.Two synthetic routes were explored. In the route A, after diosgenin was protected through the acetylation and bromine-addition reaction, the hydroxyl group was introduced at C-16 position by Oxone oxidation, followed the E/F ring-opened with dithiol and debromination to give compound 2. Then after deacetylation, silylation of C-3, C-26 hydroxyl group and reduction by LiAlH4, 22-OH was protected by acetylation, followed by desilylation with Raney Ni to finish the construct of C-25 (26) double bond. Finally, we completed the synthesis of the important intermediate 39 in 11 steps with an overall yield of 19.9% starting from diogenin.Due to the problem of excess reduction by Raney Ni, the route B was also explored. After obtained compounds 2, we built C-16(17) double bond first, and then restore the C-22 carbonyl, selective protection of C-3, 26 hydroxyl group. Finally an important intermediate 6 was obtained in 10 steps with an overall yield of 20.9% starting from Diogenin.Meanwhile, the problem of the formation of C-23 bromination by-product was resolved in the crouse of bromine-addition of Diosgenin. The organic base or epoxide can avoid the formation of C-23 bromination by-product efficiently due to their ability of eliminating the acid in reaction system.