Poster Session - Abstract # 19

A Modular Synthesis of Sanctolide A Analogs

James B. Martinez, Gihan C. Dissanayake, Paolo Alaras, Gaurav Garg, Cornelius Ndi, Jana L. Markley, Paul R. Hanson

Department of Chemistry, University of Kansas, Lawrence, KS, USA

A diversity-oriented synthesis approach was used to generate more stable, electrophilic analogs of the macrocyclic natural product sanctolide A.  The synthetic route employs a build-couple-couple-pair strategy to construct the α,β-unsaturated macrocyclic lactone/lactam skeleton of sanctolide A.  Side-chain and warhead derivatization in the build phase allowed a small library of 2-desmethyl analogs to be generated, with Michael-accepting kinetic studies in progress.  Future efforts are aimed at evaluating these analogs as modulators of nucleophilic residues on proteins such as cysteine proteases and other thiol-based enzymes.