Methodologies Toward the Enantioselective Vicinal Stereocenter Generation and Applications to Complex Molecule Synthesis

California Institute Of Technology, Pasadena CA

Investigators

Abstract

Project Summary/Abstract The lactone heterocycle is a privileged motif that appears in molecules of biological and materials importance. As a prevalent heterocyclic scaffold in chemical therapeutics, the lactone motif is featured in a number of drugs such as Irinotecan and Simvastatin. Moreover, lactones are a versatile building block in a plethora of different applications, such as in the preparation of aliphatic polyesters used as biodegradable devices in surgery and plastics. Due to their prevalence in therapies and biology, novel and innovative methodologies to access lactones in an enantioselective fashion remains highly sought after. As the construction of vicinal stereocenters, particularly all-carbon quaternary centers, is an ongoing challenge in synthetic chemistry, the disclosure of a method for the synthesis of enantiomerically enriched lactone scaffolds containing vicinal stereocenters is highly desirable. Modern methods to prepare this structural unit often require the use of a strong base, limiting applicability and functional group tolerance. The proposed research aims to develop the first asymmetric sequential visible-light photoactivation and Pd-catalyzed cycloaddition reaction capable of accessing enantiomerically enriched lactones scaffolds that possess vicinal stereocenters. If successful in developing the proposed transformation, a concise enantioselective synthesis of mehirugin C, a complex guaianolide, will be pursued to both assess the utility of the method as well as provide rapid access to a compound with interesting therapeutic indications.