Asymmetric Synthesis of (-)-Solanidine and (-)-Tomatidenol

A concise asymmetric synthesis of two naturally occurring seco-type cholestane alkaloids (-)-solanidine and (-)-tomatidenol from (-)-diosgenin with a linear reaction sequence of 12 steps and 13 steps, respectively is reported. The synthetic strategy includes the highly controlled establishment of highly functionalized octahydroindolizine ((-)-solanidine) and 1-oxa-6-azaspiro[4.5]decane cores ((-)-tomatidenol) with five stereocenters, respectively from (-)-diosgenin, featuring two stereoselective cascade transformations including a modified cascade ring-switching process of furostan-26-acid to open E-ring of (-)-diosgenin and a cascade azide reduction /intramolecular reductive amination to close E and F-rings of (-)-solanidine and (-)-tomatidenol. This work should enable further explorations of chemical and biological spaces based on solanidine, tomatidenol and related natural products.