Synthesis of Macrolide and Polyether Antibiotics and Chemical Hybrids

具有多个手性中心的大环内酯类和聚醚类抗生素由于具有许多取代基和官能团，具有显著的药理和生物活性，近年来受到了人们的广泛关注。这类复杂分子的合成为现代合成有机化学的发展做出了重大贡献。对于它们的合成，首先需要新的合成方法，主要包括在非环体系中进行立体化学控制，选择合适的保护基团，以及有效的大环化。本研究实现了一些典型的大环内酯类化合物和聚醚的高选择性高效合成。Erythronolide A是最重要和最著名的配基内酯，它是通过高效的大内酯缩合反应合成的，并借助二元酸衍生物的MMP2计算和核磁共振分析。以D-葡萄糖等新近合成的碳内酯B为原料，通过16元大环的构象控制，完全立体选择性地合成了亮烯内酯和大蒜素内酯。将热力学条件下基于络合控制的四氢呋喃立体选择性合成新方法应用于聚醚抗生素、拉沙洛西德A和异沙柳酸A的立体选择合成。

Macrolide and polyether antibiotics with multiple chiralty centers, owing to the presence of many substituents and functional groups, have received much recent synthetic attention because of their significant pharmacological and biological activities. The synthesis of such complex molecules makes sigumificant contributions to the progress of modern synthetic organic chemistry. For their syntheses new synthetic methodologies mainly consisting of means of stereochemical control in acyclic systems, selective use of suitable protecting groups, and efficient macro-cyclization are primarily required. In this study, highly selective and efficient syntheses of some typical macro-lides and polyethers have been achieved. Erythronolide A, the most important and famous aglycon, was synthesized via a extremely efficient macrolactonization with the aid and NMR analysis of MMP2 calculation of a secoacid derivative. Leuconolides and maridonolides were also synthesized completely stereoselectively from carbonolide B, recently synthesized from D-glucose, etc., via conformational control of 16-membered macro-rings. A new stereoselective synthetic method of tetrahydrofurans based on chelation control under thermodynamic conditions was applied to the stereoselective synthesis of polyether antibiotics, lasalocid A and isolasalicid A.