Expedient Synthesis of the Proposed Structure of Cryptoconcatone H Exploiting Hidden Symmetry

Abstract

Synthesis of the originally proposed structure of the styryl tetrahydropyranol-dihydropyranone natural product cryptoconcatone H from C2 -symmetric (±)-1,8-nonadiene-4,6-diol is reported. Desymmetrization by Mitsunobu reaction with crotonic acid established the requisite inter-ring stereochemical relationship and was followed by a highly diastereoselective Re2O7 catalyzed Prins cyclization with cinnamaldehyde to construct the 2,4,6-cis-tetrahydropyranol ring. Ring-closing metathesis resulted in formation of the dihydropyranone ring and completed of the synthesis in three steps and 32% overall yield. The brevity of the synthesis is the result of the recognition of hidden, inter-ring symmetry in the target and the ensuing choice of an appropriately symmetric diol as our starting material.