Highly stereoselective synthesis of complex natural products.

本研究的目的是开发一种新的合成方法，一系列复杂的天然大环内酯，通过方便和有效的合成许多片段和他们的耦合，从廉价的材料，如葡萄糖。在过去三年的研究中，我们主要取得了以下成果：最近，我们发展了两种大环的构建方法：开环酸的大环内酯化和开环膦酸酯的Horner-Emmons环化。这种方法，结合计算机辅助构象分析（使用分子力学和分子轨道计算）和关键中间体的结构设计，现在被应用于抗肿瘤的海洋大环内酯类化合物tedanlitazone的合成研究。以羟基异丁酸甲酯为起始原料，立体选择性地合成了C1-C12和C13-C23两个片段，并偶联得到开环酸，开环酸有效地转化为18-元内酯，这是合成替丹鲁肽的关键中间体。立体选择性合成的新片段，这将被转化为另一个开环酸，相应的内酯，和tedanlavin更合理，也完成了。

The purpose of this research was to develop a new synthetic methodology of a series of complex natural macrolides through convenient and efficient syntheses of many fragments and their couplings, starting from inexpensive materials such as glucose. The following results were mainly obtained during the past three years research.Recently, we developed two methods for the construction of macro-rings ; macrolactonization and Horner-Emmons cyclization of the corresponding seco-acids and aldehyde-ketophosphonates, respectively. This methodology, combined with computer-aided conformational analysis (using both molecular mechanics and molecular orbital calculations) and structural design of key intermediates, was now applied to synthetic studies of tedanolide, an antitumor marine macrolide. Two fragments, C1-C12 and C13-C23, were synthesized stereoselectively staring from methyl hydroxyisobutyrates and coupled to give a seco-acid, which converted efficiently to an 18-mombered lactone, a key intermediate for the synthesis of tedanolide. Stereoselective syntheses of new fragments, which will be converted to another seco-acid, the corresponding lactone, and tedanolide more reasonably, were also completed.