Synthesis of a Small-Molecule Library with Skeletal Diversity from Hemslecin A via the Reaction-Discovery Strategy.

An efficient reaction tool box was developed for the synthesis of skeletally diverse and stereochemically complex templates for a small-molecule library based on the common synthon Q, which was prepared from hemslecin A in four steps. The reaction tool box comprises three acid-promoted rearrangements: semipinacol, Wagner-Meerwein, and cyclopropylmethyl cation rearrangements. More importantly, a Mn-mediated C-H oxidation was developed to achieve a high level of complexity, which provides a new entry for C-H functionalization of inert angular methyl groups in the chemistry of triterpenes. Our reaction-discovery strategy based on hemslecin A provides a basis for the inherent chemistry of triterpenes and could be applied for the further transformation of triterpenes.