Asymmetric synthesis of (−)-solanidine and (−)-tomatidenol

Abstract

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 ((−)-tomatidenol) cores with five stereocenters, respectively, from (−)-diosgenin, featuring two stereoselective cascade transformations including a modified cascade ring-switching process of furostan-26-acid to open the E-ring of (−)-diosgenin and a cascade azide reduction/intramolecular reductive amination to close the 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.