CHIRAL CROTYLBORONATIES--METHODOLOGY AND SYNTHESIS

手性巴豆基硼酸酯--方法学和合成

• 批准号: 3294872
• 负责人: WILLIAM R ROUSH
• 金额: $ 14.83万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1992-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3294872
• 关键词: acetates; allyl compound; antifungal agents; antiprotozoal agents; boronic acids; croton oil; drug design /synthesis /production; enolate; propionates; stereoisomer

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.

高效的立体选择性和对映选择性构建 非环状立体中心的复杂阵列构成了 现代合成有机化学中最有趣的挑战。 在大环内酯类中， 聚醚抗生素和许多其他生物活性 有机化学家理应设计出 切实可行、有效和适用于董事会的方法 问题的光谱。 我们建议的研究是针对发展一个 聚丙酸酯（-CHMe-CHOH-CHMe-）的通用溶液 和聚乙酸酯（-CHOH-CH 2-CHOH）无环立体化学 问题 在初步工作中，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。 在未来四年计划的研究中， 在这一年期间，我们打算探讨的范围和一般性， 这些试剂，探索不对称的起源，并开发第二个 具有增加的、接近完美水平的 对映选择性 我们还打算将这种方法应用于 合成天然产物的生物合成 起源 建议的靶点包括静脉曲张链球菌素的ansa链 D（具有显著抗病毒活性的安莎霉素抗生素）和 巴弗洛霉素A1（一种新的环内酯家族成员， 具有一系列重要生物学特性的大环内酯类 包括抗寄生虫和抗真菌活性）。 合成 目标优先级低于方法 调查事务所 如果我们的目标得以实现， 手性烯丙基硼酸酯家族，其功能为高度 对映选择性乙酸酯和丙酸酯烯醇化物等价物，和 将大大扩大试剂的范围， 对映体和非对映体选择性的有机化学家 构建复杂的生物活性分子。