Part I: Catalytic Asymmetric Total Synthesis of (-)-Rocaglamide. Part II: Selenium Dioxide Mediated Synthesis of Isotetronic Acids. Part III: Synthesis of Analogues of Rocaglamide

Abstract

Part I: The first catalytic asymmetric total synthesis of (-)-rocaglamide was accomplished in twelve steps with 3.5% overall yield. An asymmetric Pd0 catalyzed Nazarov-type cyclization gave a key intermediate in 89/11 e.r. and 70% yield. Part II: Oxidation of α,β-unsaturated methyl ketones with selenium dioxide leads to a cascade of reactions culminating in the formation of isotetronic acids. This efficient new method starts from commercially available starting materials and gives complex isotetronic acids in only one step from corresponding ketones. Furans and pyrones can also be obtained using modified substrates. Part III: A number of analogues of rocaglamide were synthesized. Preliminary examinations of their biological activities have shown some promising leads for the development of potential cancer therapeutic agents. Further studies are currently underway.