ACYCLIC STEREOSELECTION IN NATURAL PRODUCT SYNTHESIS

这个项目的长期目标是解决这些问题 引入复杂有机化合物的合理合成 分子的立体化学，无论是相对的还是绝对的。在 提出了五年计划，将进行几种类型的研究 被执行。最基本的将是物理有机 研究锂和镁烯醇酸盐，重要 有机合成的中间体。这些研究将试图 评估聚合对反应性的重要性，特别是对 立体化学。研究方向是开发一种 用于催化不对称羟醛缩合反应的协议 还将进行易于获得的硼烯醇酸盐。这个 两个较少研究的班级的立体化学人格 试剂--烯醇酸镁和金属烯胺--将 系统地调查了。反应的立体化学 含有亲核烯烃的免疫离子和硫离子将 接受调查。一种用于立体选择的有效协议 构象柔性分子的结构将是 进一步发展。这一策略采用了高度的立体选择性 羟醛反应，再加上已知的进一步反应 具有高选择性的转移手性。特定的序列以 将使用顺序Aldol、Claisen和Mislow/Evans进行研究 重新安排准备有三块的积木 立体中心。该方法适用于全合成。 天然产物ACRL毒素IIIA和粘菌胺。它的用途 不对称羟醛的手性α-硅氧基酮 建筑将进一步发展和应用于 利福霉素S安沙链的合成。最后，赤藓内酯A 将作为开发Aldol战略的练习进行综合。 这项研究项目的主题是立体化学 综合，一个与现代医学密切相关的话题 化学反应。

The long term goal of this project is to address the problems introduced into the rational synthesis of complex organic molecules by stereochemistry, both relative and absolute. In the five-year program proposed, several types of studies will be carried out. The most fundamental will be physical organic investigations of lithium and magnesium enolates, important intermediates in organic synthesis. These studies will try to assess the importance of aggregation on reactivity, specifically on stereochemistry. Reseach directed toward the development of a protocol for catalytic, asymmetric aldol reactions using the readily-available boron enolates will also be carried out. The stereochemical personalities of two less-studied classes of reagents--magnesium enolates and metalloenamines--will be systematically investigated. The sterochemistry of the reactions of immonium ions and thionium ions with nucleophilic alkenes will be surveyed. A productive protocol for the stereoselective construction of conformationally-flexible molecules will be further developed. This strategy employs a highly stereoselective aldol reaction, coupled with further reactions that are known to transfer chirality with high selectivity. The specific sequence to be studied will utilize sequential aldol, Claisen, and Mislow/Evans rearrangement ot prepare building blocks having three stereocenters. The method will be appleid to the total synthesis of the natural porducts ACRL toxin IIIA and myxalamide. The use of chiral alpha-silyloxy ketones for asymmetric aldol constructions will be further developed and applied to the synthesis of the rifamycin S ansa chain. Finally, erythronolide A will be synthesized as a exercise in development of aldol strategy. The main theme of this research project is stereochemistry in synthesis, a topic of great relevance to modern medicinal chemistry.