Highly selective fine organic synthesis

本研究的目的是通过开发一种新的方法来选择性和高效地合成非常复杂的分子，如大环内酯和聚醚抗生素以及海洋聚醚大环内酯，为现代精细有机合成化学的进步做出贡献。在过去四年的研究中，主要获得了以下五个成果：1。大环内酯类化合物的合成：利用MM2-CONFLEX3计算和二次酸衍生物的核磁共振分析，通过极高效的大环化反应合成了最重要的糖醛酸red molide A，并通过16元大环的构象控制，从Carbonolide B完全立体选择性地合成了Carbonolide A、leuconolides和maridonolides。聚醚的合成：用一种常见的方法完成了高度立体选择性的络合物异丙酸A、激光酸A、盐霉素和溶菌素的合成。聚醚-大环内酯的合成：完成了四个软海绵素B片段的立体选择性合成，片段之间的偶联正在进行中。不对称自由基环化：在路易斯酸的存在下，通过乙炔和α、β -不饱和酯之间的不对称自由基环化，建立了一种合成光学活性五元环和六元环的新方法。杂Diels-Alder反应：通过杂Diels-Alder反应，在二苯胺和二烯衍生物之间一步合成了具有光学活性的二氢吡啶衍生物。该方法成功地合成了一种多胺类生物碱——大麻素。

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.