CHIRAL CROTYLBORONATIES--METHODOLOGY AND SYNTHESIS

高效的立体和对映选择性结构 非循环立体中心的复杂阵列构成了 现代合成有机化学中最耐人寻味的挑战。 大环内酯类化合物中大量的无环立体中心， 聚醚抗生素和许多其他生物活性物质 天然产物理应由有机化学家来设计 实用、高效、适用于董事会的方法 一系列问题。 我们建议的研究旨在开发一种 聚丙酸酯(-CHMe-CHOH-CHMe-)的一般溶液 和聚乙酸酯(-CHOH-CH2-CHOH)非环立体化学 有问题。在前期工作中，我们开发了一类 酒石酸酯改性的烯丙基和巴豆基硼酸酯 高对映选择性和非对映选择性反应 非手性和手性醛。在未来四年计划进行的研究中 年内，我们打算探讨 这些试剂，探索不对称的起源，并发展第二 新一代试剂增加，近乎完美的水平 对映体选择性。我们还打算将这一方法应用于 丙基生物合成天然产物的合成 起源。建议的靶标包括链状病毒的ANSA链 D(一种具有显著抗病毒活性的安沙霉素抗生素)和 巴菲尔霉素A1(新的湿润内酯家族成员 具有一系列重要生物学特性的大环内酯类化合物 包括抗寄生虫和抗真菌活性)。合成材料 目标的优先级将低于方法论 调查。如果我们的目标实现了，我们将开发出一种 手性烯丙基硼酸酯家族，其功能与 对映体选择性醋酸酯和丙酸烯醇类等价物，以及 将大大扩大可供使用的试剂范围 研究对映体和非对映选择性的有机化学家 构建具有生物活性的复杂分子。

The efficient stereo- and enantioselective construction of complex arrays of acyclic stereocenters constitutes one of the most intriguing challenges in modern synthetic organic chemistry. The multitude of these acyclic stereocenters in macrolides, polyether antibiotics and numerous other biologically active natural products behooves the organic chemist to devise methodology that is practical, efficient and applicable to a board spectrum of problems. The studies we propose are directed towards the development of a general solution to the polypropionate (-CHMe-CHOH-CHMe-) and polyacetate (-CHOH-CH2-CHOH) acyclic stereochemical problems. In preliminary work we have developed a class of tartrate ester modified allyl and crotylboronic esters that undergo highly enantioselective and diastereoselective reactions with achiral and chiral aldehydes. In studies planned for the next four year period, we intend to explore the scope and generality of these reagents, probe the origin of asymmetry and develop second generation reagents with increased, near perfect levels of enantioselectivity. We also intend to apply this methodology in the synthesis of natural products of propiogenic biosynthetic origin. Suggested targets include the ansa chain of streptovaricin D (an ansamycin antibiotic with significant anti-viral activity) and bafilomycin A1 (a member of the novel hygrolide family of macrolides that have a range of significant biological properties including antiparasitic and antifungal activity). The synthetic objectives will receive lower priority than the methodological investigations. If our goals are met, we will have developed a family of chiral allylboronates that function as highly enantioselective acetate and propionate enolate equivalents, and will have greatly expanded the scope of reagents available to the organic chemist for the enantio- and diastereoselective construction of complex, biologically active molecules.