Novel Asymmetric Routes to 2-Oxetanones and their Application

Texas A&M Research Foundation, College Station TX

Investigators

Abstract

Under prior NSF support, the Romo Group at Texas A&M University developed practical, catalytic asymmetric routes to both bicyclic and tricyclic beta-lactones from ketoacid substrates employing a nucleophile-catalyzed aldol lactonization process (NCAL). Building on a growing understanding of the NCAL process, novel transformations of these beta-lactones and new variants of the NCAL process including dynamic kinetic resolution are being pursued with the support from the Chemical Synthesis Program of the Division of Chemistry. The utility and practicality of these methods will be demonstrated in the context of natural product total synthesis targeting the completion of spongiolactone and curcumalactone/curcumanolide A. In addition, specific cellular probes based on these bioactive natural products will be prepared to serve as basic proteomics tools in collaborative studies. Mechanistic studies of ammonium enolates directed toward development of new reaction manifolds involving these versatile intermediates are being pursued in collaboration with Prof. Dean Tantillo (UC Davis). The practice of organic synthesis continues to be instrumental in propelling significant advances in the areas of human and animal health among other fields. Successful development of the proposed methods for beta-lactones will impact the field of organic synthesis pertinent to the pharmaceutical and agricultural industries as the methods being developed are robust and "user friendly". In addition, synthesis of the targeted biologically active natural products by synthetic methods being developed will have broader impacts in enabling the further understanding of fundamental cellular processes and enabling collaborations with computational chemists and biochemists/cell biologists. The Romo Group has initiated a number of outreach initiatives including a Natural Products Discovery Lab during the Annual Chemistry Open House, combining NSF-funded research and teaching by importing new experiments into the chemistry major's laboratory, and developing multimedia presentations to demonstrate the societal relevance of organic synthesis.