Synthetic Studies on Protein Phosphatase Inhibitor Dysidiolide

点击翻译按钮获取中文摘要

Dysidiolide, a novel sesterterpenoid isolated from the Caribbean sponge Dysidia eiheria de Laubenfels, exhibits inhibition of the protein phosphatase cdc25A.Dysidiolide possesses a unique carbon skeleton with structural features that find no precedent in nature. Thus, its unique structure and biological activity prompted me to undertake the synthetic studies of dysidiolide. I have achieved following three heading in this study.1. Exploitation of Synthetic Method for Decalin Part of Dysidiolide using Intramolecura Diels-Alder ReactionI developed synthetic method for decalin part of dysidiolide using model compound. This synthesis involves preparation of alpha, beta-unsaturated lactone by intramolecura Diels-Alder reaction, stereoselective methylation by Me_2CuLi at C-6 position and stereoselective alkylation at C-7 position.2. Formal Synthesis of (*)-DysidiolideDecalin part of dysidiolide was synthesized according to above method. Deoxyganation of the C-12 and C-24 positions and extension of side chain completed the formal synthesis of (*)-dysidiolide.3. Synthesis of Optically Active Cyclohexene Derivative Using LipaseOptically active cyclohexene derivative was synthesized by optical resolution using Lipase AK.This compound is useful for the synthesis of optically active dysidiolide as a starting material.The synthesis of optically active dysidiolide is now in progress.