Synthetic Studies on Protein Phosphatase Inhibitor Dysidiolide

Dysidiolide是一种从加勒比海海绵disidia eiheria de Laubenfels中分离出来的新型酯萜类化合物，具有抑制蛋白磷酸酶cdc25A的作用。二硫醚具有独特的碳骨架，其结构特征在自然界中没有先例。因此，它独特的结构和生物活性促使我承担了二硫醚的合成研究。在这项研究中，我实现了以下三个目标：1。分子内Diels-Alder反应合成二苯二甲酸酯十萘部分方法的开发利用模型化合物合成二苯二甲酸酯十萘部分的方法。该合成包括通过分子内Diels-Alder反应，Me_2CuLi在C-6位置的立体选择性甲基化和C-7位置的立体选择性烷基化制备α， β -不饱和内酯。按上述方法合成了(*)-二苯二甲酸乙酯的十萘部分。C-12位和C-24位的脱氧和侧链的延伸完成了(*)-二硫代二聚醚的正式合成。利用脂肪酶合成旋光性环己烯衍生物以脂肪酶AK为溶剂，采用光学拆分法合成了旋光性环己烯衍生物。该化合物可作为合成光活性二硫醚的起始原料。目前，光活性异二醇内酯的合成正在进行中。

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.