The Synthesis Of Osladin And Polypodoside A Aglycones Using Diosgenin Complete Skeleton

As a part of the project aiming for a rational utilization of steroidal sapogenins in our group, the research described in this dissertation explored the syntheses of the sapogenins of osladin and polypodside A, two structurally related steroid sweeteners, from the intact skeleton of diosgenin. The progress we made is listed below:With Ac2O/BF3·Et2O as activating system and Et3SiH as hydrogen source, a direct reductive opening of the E-ring of steroidal sapogenins has been realized for the first time. Obtaining the unwanted22S-configuration in this reaction urged us to pursue another solution.A higly efficient method, which involves the reductive opening of the F-ring of diosgenin and an activation relayed process to rearrange EF-ring (opening the E-ring and reclosing the F-ring), has been developed to provide the desired22R-configured product. Employing this method, we have prepared a key lactone intermediate in Nishizawa’s osladin synthesis in only five steps and an overall yield of63%, therefore accomplished a formal synthesis of osladin and consequently the syntheses of the sapogenins of osladin and polypodoside A.In this way, we have developed two complementary methods for E-ring opening of steroidal sapogenins which enable easy access to both22S-and22R-products, hence, filled a vacancy in and broadened greatly the modes of utilizing the intact skeletons of steroidal sapogenins in organic synthesis. Furthermore, the intramolecular activation relayed strategy provided intermdiates with six-memebered lactone and C16a-I; the ease of functional-group manipulations gives golden opportunities for further structure modifications in the natural products synthesis.