Synthetic research of macrolide and polyether antibiotics.

大环内酯类和聚醚类抗生素的合成研究。

基本信息

批准号：
04557096
负责人：
YONEMITSU Osamu
金额：
$ 7.55万
依托单位：
Okayama University of Science (1994)Hokkaido University (1992-1993)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

The purpose of this research was to contribute to the progress of modern fine organic synthetic chemistry as a basis of the creation of new medicines throrgh the development of a new methodology for selective and efficient syntheses of very complex molecules such as macroide, polyether antilbiotics and marine polyether-macrolides. During the past three years research the following three results were mainly obtained.1. Synthsis of macrolides : A new stereoselective syntheses of erythromolide A,the most important aglycon, was completed via an extremely efficient macrolactionization with the aid of MM2-CONFLEX3 calculation and NMR analysis of seco-acid derivatives. The representative aglycons in carbomycin series such as carbonolide A,leuconolides, and maridonolides were also synthesized completely stereoselectively from carbonolide B through conformational control of 16-membered macro-rings. Computer-aided conformational analysis and structural design of key intermediates for the stereoselective synthesis of tedanolide, an anti-tumor marine macrolide, were successfully applied, and an 18-membered lactone was synthesized highly efficiently.2. Synthesis of polyethers : Highly stereoselective syntheses of complex isolasalocid A,lasalocid A,salinomycin, and lysocellin by a common methodology using a new method for the construction of substituted tetrahydofuran and tetrahydropyran rings and MPM type protective groups were completed.3. Synthesis of polyether-macrolides : Four fragments (I : C1-C15, II : C16-C26, III : C27-C36, IV : C37-C54) of halichondrin B were stereoselectively synthesized, and couplings among the fragments were completed to give C1-C36 and C16-C54 intermediates. In order to complete the total synthesis of halichondrin B final couplings are now in progress.

这项研究的目的是为现代精细的有机合成化学的进步做出贡献，这是创造新药物的基础，从而开发了一种新方法，以选择性和有效的合成，这些方法是宏观物质，聚醚抗生物学和海洋多乙烯聚乙烯和海洋多乙乙量的非常复杂的分子。在过去的三年中，研究以下三个结果主要获得。1。大环内酯类的合成：最重要的AglyCon的红细胞固醇A的新立体选择合成是通过非常有效的宏观分化来完成的，借助MM2-Conflex3计算和NMR分析了SECO酸性衍生物。碳霉素系列中的代表性aglycons，例如碳醇A，白细胞和脂肪诺酚，也通过对16元的宏环的构象控制完全立体地从Carbonolide B中完全合成。成功地应用了计算机辅助构象分析和关键中间体Tedanolide的立体选择性合成，并成功地应用了抗肿瘤海洋大花环，并且合成了18元的乳酮。聚乙烯的合成：通过一种常见方法论，使用一种新方法来构建取代的四氢呋喃和四氢吡喃的环和mpm型保护组，使用一种新方法，使用了一种新方法，使用了一种共同的方法来完成聚乙烯的合成：高度立体选择性合成。聚醚甲莫里德蛋白的合成：哈丘顿蛋白B的四个片段（I：C1-C15，II：C16-C26，III：C27-C36，IV：C37-C54）B刻有稳定性合成，并完成了片段之间的耦合，从而使C1-C36和C1-C16-C54 IntermediaseS均可完成。为了完成Halichondrin B的总合成，最终耦合现在正在进行中。