NEW APPROACH TO ENANTIOPURE OXYGEN HETEROCYCLES

制备对映体纯氧杂环的新方法

• 批准号: 6401769
• 负责人: JOHN P WOLFE
• 金额: $ 3.14万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6401769
• 关键词: catalyst; chemical addition; chemical synthesis; ketal; oxygenous heterocyclic compound; stereoisomer

A wide variety of heterocyclic compounds, including compounds such as morpholines, dihydropyrans, and dihydrofurans have been shown to have important biological activities. This proposal describes a new approach to the synthesis of enantiopure heterocycles which contain an oxygen in the heterocyclic ring. This new synthetic approach is based on a method for the catalytic asymmetric addition of alkyltitanium reagents to achiral acetals. The addition to providing a new route to chiral secondary and tertiary alcohols, this method provides a new route to enantiopure heterocycles if cyclic acetals are used as substrates; the alcohol products resulting from the addition to the acetal may be further transformed to heterocycles. This proposal details the development of the asymmetric addition methodology with respect to substrate scope, catalyst development, and optimization of the reaction conditions. General strategies which could be used to transform the addition products into heterocycles are described. These strategies are then applied to the synthesis of the biologically active heterocycles SR 144190 (a NK-1 inhibitor), Mangone- A (a PAF antagonist), and Sesaminone (an antibiotic).

各种各样的杂环化合物，包括诸如吗啉、二氢吡喃和二氢呋喃的化合物已被证明具有重要的生物活性。该建议描述了一种新的方法来合成在杂环中含有氧的对映纯杂环。这种新的合成方法是基于一种催化不对称加成烷基钛试剂的非手性缩醛的方法。除了提供一种新的手性仲醇和叔醇的路线，如果使用环状缩醛作为底物，该方法提供了一种新的对映体纯杂环的路线;从添加到缩醛中产生的醇产物可以进一步转化为杂环。该提案详细介绍了不对称加成方法学在底物范围、催化剂开发和反应条件优化方面的发展。描述了可用于将加成产物转化为杂环的一般策略。然后将这些策略应用于生物活性杂环SR 144190（NK-1抑制剂）、曼戈内- A（PAF拮抗剂）和芝麻酮（抗生素）的合成。