Development of highly selective reactions and application to the synthesis of complex natural products.

从现成的材料中合成高价值有机化合物的研究项目，对于我们这个自然资源非常贫乏的国家的伟大未来来说，现在是极其重要的。由高官能度、区域和立体选择性反应组成的现代精细合成有机化学的发展是这类项目成功的关键。最近，我们计划以糖，特别是最容易获得的D-葡萄糖为原料，通过共同的合成方法合成一些具有代表性的大环内酯类和聚醚类抗生素，主要包括：1)通过D-葡萄糖的C-3和C-5位取代基的环或非环立体控制引入来合成三个连续的手性中心；2)构建至少10：1的新的手性中心；1通过高度立体选择性反应进行立体选择性；3)选择性地使用苯基型羟基保护基(MPM，MPM)DMPM)可被DDQ氧化去除。在我们的合成方案中，到目前为止获得了以下结果。1)开发了可通过DDQ氧化或Raney Ni催化氢解选择性去除的苄基型(Bn，MPM，DMPM)保护基团。2)立体控制酸催化环化合成取代四氢呋喃和四氢吡喃。3)以葡萄糖为手性起始原料，高立体选择性地合成了具有甲基内酯、匹克罗内酯、赤内酯A和泰隆内酯等复杂结构的大环内酯苷元。4)以D-葡萄糖、D-甘露醇和L-乳酸为原料，实现了多醚抗生素盐霉素的高立体选择性合成。

Research programs on the synthesis of organic compounds with high value from readily available materials are now extremely important for the great future of our country having very poor natural resources. Development in the modern fine synthetic organic chemistry consisting of highly functional, regio, and stereoselective reactions helds the key to success in such programs.Recently, we planned to synthesize some representative macrolide and polyether antibiotics from sugars, especially most readily available D-glucose, by a common synthetic methodology consisting mainly of 1) synthesis of three contiguous chiral centers by cyclic or acyclic stereocontrolled introduction of substituents at C-3 and C-5 positions of D-glucose, 2) construction of new chiral centers with at least 10 : 1 stereoselction by use of highly stereoselective reactions, 3) selective use of benzyl-type protecting groups for hydroxy groups (MPM, DMPM) removable by DDQ oxidation.In our synthetic programs, the following results so far obtained. 1) Benzyl-type (Bn, MPM, DMPM) protecting groups selectively removable by DDQ oxidation or catalytic hydrogenolysis with Raney Ni were developed. 2) Stereoselective synthesis of substituted tetrahydrofurans and tetrahydropyrans by stereocontrolled acid-catalyzed cyclization. 3) Highly stereoselective synthesis of macrolide aglycons having complex structures such as methynolide, pikronolide, erythronolide A, and tylonolide from Dglucose as a chiral starting materials was completed. 4) Highly stereoselective synthesis of the polyether antibiotic salinomycin from D-glucose, D-mannitol, and L-lactic acid was achieved.