Synthesis Of Steroidal Alkaloid Solanidine And Demissidine

Steroidal alkaloids are secondary metabolites isolated from plants and marine invertebrates. They have complex and diverse chemical structures and demonstrates a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, etc. The research for steroidal alkaloids will be helpful for the discovery and development of new drugs and agricultural agents. Based on the obtained achievement by our group from the project of the rational utilization of steroidal sapogenins, my master thesis focused on the syntheses of steroidal alkaloids solanidine and demissidine starting from sapogenins.The structures of solanidine and demissidine resemble those of diosgenin and tigogenin, with main differences being the arrangements of the EF ring systems. The C16, C22, and C26 of solanidine/demissidine all connect with the same nitrogen atom, forming a 5,6-fused bicycle system, while those of steroidal sapogenins connect with two oxygen atoms to form a 5,6-spiroketal. The configurations at C25 are also different: the former is S and the latter is R. Therefore, the main chalenge is how to convert three carbon-oxygen bonds into three carbonnitrogen bonds effectively and stereoselectively and to epimerize the configuration at C25.Our synthesis of solanidine started from a reductive opening of the ring F of diosgenin, which was followed by an intramolecular activation relayed strategy process to open the ring E and halogenate C16, giving 2-20 in high yield. Treating 2-20 sequentially with sodium azide and K2CO3 smoothly converted the C16α-Br/I to C16β-azide and epimerized the stereochemistry of C25. The resulting azide 2-17 underwent an intramolecular Schmidt reaction to give imine 2-19, which underwent a stereoselective imine reduction/intramolecular aminolysis to set the desired C22 configuration, providing lactam 2-26 in good yield. After reducing 2-26 with red aluminum, solanidine was synthesized from diosgenin acetate in eight steps with an overall yield of 16%.Through a similar strategy, demissidine was synthesized from tigogenin acetate in eight steps with an overall yield of 17%.