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Highly selective fine organic synthesis

高选择性精细有机合成

基本信息

批准号：
02403026
负责人：
YONEMITSU Osamu
金额：
$ 20.54万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1993
项目状态：
已结题

项目摘要

The object of this research was to contribute to the progress of modern fine organic synthetic chemistry through the development of a new methodology for selective and efficient syntheses of very complex molecules such as macrolide and polyether antilbiotics and marine polyether-macrolides. During the past four years research the following five results were mainly obtained.1. Synthsis of macrolides : Erythromolide A, the most important aglycon, was synthesized via an extremely efficient macrolactionization with the aid of MM2-CONFLEX3 calculation and NMR analysis of a seco-acid derivative, Carbonolide A, leuconolides, and maridonolides were also synthesized completely stereoselectively from carbonolide B through conformational control of 16-membered macro-rings.2. Synthesis of polyethers : Highly stereoselective synthesis of complex isolasalocid A, lasalocid A, salinomycin, and lysocellin by a common methodology was completed.3. Synthesis of polyether-macrolides : Stereoselective synthesis of four fragments of halichondrin B was completed, and coupling among the fragments is in progress.4. Asymmetric radical cyclization : A new method for the synthesis of optically active five and six membered rings was developed via asymmtric radical cyclization between an acetylene and an alpha, beta-unsaturated ester in the presence of a Lewis acid.5. Hetero Diels-Alder reaction : One-step synthesis of optically active dihydropyridine derivatives was developed via a hetero Diels-Alder reaction between tosylimines and diene derivatives. This method was successfully applied for the synthesis of a polyamine alkaloid, cannabisativine.

本研究的目的是通过发展一种新的方法来选择性和有效地合成非常复杂的分子，如大环内酯和聚醚抗生素和海洋聚醚-大环内酯，以促进现代精细有机合成化学的进步。在过去四年的研究中，主要取得了以下五个方面的成果.大环内酯类的合成：通过开环酸衍生物的MM 2-CONFLEX 3计算和NMR分析，通过高效的大环内酯化反应合成了重要的糖苷配基赤藓醇内酯A，并通过16元大环构象控制，完全立体选择性地从碳环B合成了碳环内酯A、明白内酯和玛丽多内酯。聚醚的合成：采用常规方法高立体选择性地合成了异拉萨洛西A、拉沙洛洛西A、盐霉素和溶胞素复合物.聚醚大环内酯类化合物的合成：完成了软海绵素B四个片段的立体选择性合成，片段间的偶联正在进行中.不对称自由基环化：发展了一种新的合成光学活性五元环和六元环的方法，即在刘易斯酸存在下，乙炔与α，β-不饱和酯发生不对称自由基环化反应. Heavy Diels-Alder反应：通过对甲苯磺酰亚胺与二烯衍生物之间的杂Diels-Alder反应，一步合成了光学活性的二氢吡啶衍生物。该方法已成功地应用于多胺生物碱大麻素的合成。