Part 1: Total Synthesis of Clavosolide A Part 2: Total Synthesis of Subglutinols A and B

Abstract

Nature provides an abundant source of small molecules that can be used to interrogate biological systems. However, these compounds are often available in limited quantities from natural sources and must be synthesized in order to: 1) accumulate useful amounts for further study; 2) provide an efficient means to introduce structural modifications to achieve analogues. Part I demonstrates the asymmetric total synthesis of (-)-clavosolide A, showcasing the tandem allylic oxidation/oxa-Michael reaction in the stereoselective formation of the 2,3-trans-2,6-cis-tetrahydropyran core. Part II demonstrates the total synthesis of the immunosuppressive compounds, subglutinols A and B through reductive deoxygenation and cross-metathesis/intramolecular SN2ʹ reactions from a common intermediate to form the substituted 2,3-trans-2,5-trans-tetrahydrofuran and 2,3-trans-2,5-cis-tetrahydrofuran cores (subglutinol A and B respectively. Preliminary structure-activity relationships as well as biological studies are presented.