Synthetic studies toward the total synthesis of palmerolide A

ORGN 780

Krishna P Kaliappan, kpk@chem.iitb.ac.in, Sandip A Pujari, sapujari@chem.iitb.ac.in, and Gowrisankar Parthasarathy. Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, India

Palmerolide A display potent and selective cytotoxicity against melanoma cancer cell line and also found to inhibit V-ATPase. From structural point of view, it is synthetically challenging 20-membered macrocyclic polyketide having five chiral centers with an unstable enamide side chain and core1,3-diene. Although its structure was proposed on the basis of high field NMR spectroscopic analysis, absolute stereochemistry was elegantly reassigned based on Brabander's synthesis, which was further confirmed by Nicolaou's synthesis. In view of its structural complexity and excellent medicinal properties, we developed interest in the synthesis of palmerolide A. Our group had earlier reported the synthesis of the northern hemisphere of originally proposed structure of palmerolide A. In this presentation, our efforts towards the total synthesis of palmerolide A, using Julia- Kocienski olefination, Yamaguchi esterification and ring closing metathesis as key reactions will be discussed.