Total Synthesis of Bistramide A and Its 36(Z) Isomers: Differential Effect on Cell Division, Differentiation, and Apoptosis (pages 7452–7466)
Dr. Loïc Tomas, Dr. Gustav Boije af Gennäs, Dr. Marie Aude Hiebel, Dr. Peter Hampson, Dr. David Gueyrard, Dr. Béatrice Pelotier, Prof. Jari Yli-Kauhaluoma, Prof. Olivier Piva, Prof. Janet M. Lord and Prof. Peter G. Goekjian
Article first published online: 26 APR 2012 | DOI: 10.1002/chem.201102462
Actin versus apoptosis–not so EZ: The total synthesis of bistramide A and its 36(Z),39(S) and 36(Z),39(R) isomers (see figure) relies on a novel synthesis of exocyclic enol ethers for the spiroketal fragment, a kinetic oxa-Michael cyclization for the tetrahydropyran fragment, and an asymmetric crotonylation for the amino acid fragment. These compounds show distinctly different effects on cell division, differentiation, and apoptosis, thus suggesting that there are multiple independent biological activities of the natural product.