CHIRAL SYNTHONS FOR SYNTHESIS OF BIOLOGICALLY ACTIVE MOLECULES

不对称合成领域的重要性由于 更加重视活性对映体的评价和营销 一种药物，与其相应的外消旋体相对。因此，不对称 多种手性生物活性分子的合成方法 以及它们的结构类似物都是化学家非常感兴趣的 以及制药业。PI的研究计划的目标是 开发一种新的有用的不对称合成方法 各种生物活性分子。这项提议的第一个目标是 是制定了一些功能化的制备方法 手性非外消旋羟基砜和羟基磷酸盐。面包师酵母 适当的羰基前体的还原或脂肪酶的催化 外消旋醇的拆分将被仔细检查为 HIGH中这些手性合成子产生的可能途径 光学纯度和所需的配置。的第二个目标 该提议是为了证明这些手性物质的合成用途。 中间体。在这方面，重要的是提到 具有磺酰基和膦酸基的中间体是众所周知的 因为它们的合成多功能性。有人建议开发一些新的 利用这些手性合成子的独特化学成分的方法学。 更具体地说，一些分子内的环化反应 不饱和的酰基砜和酰基膦酸酯有很多合成 潜在的和需要调查的。最后，建议 一些已知生物活性的大环内酯类化合物的合成 和Lasiodiplodin，使用从这项工作中产生的中间体。

The area of asymmetric synthesis has grown in importance due to the increased emphasis on evaluation and marketing of the active enantiomer of a drug as opposed to its corresponding racemate. Hence, asymmetric synthetic approaches to a variety of chiral, biologically active molecules as well as their structural analogs are of much interest to the chemist and the pharmaceutical industry. The goal of the PI's research program is to develop new and useful methodology for the asymmetric synthesis of a variety of biologically active molecules. The first goal of this proposal is to develop methods for the preparation of a number of functionalized chiral nonracemic hydroxysulfones and hydroxy phosphonates. Bakers' yeast reductions of appropriate carbonyl precursors or the lipase catalyzed resolution of racemic alcohols will both be carefully examined as potential routes for the generation of these chiral synthons in high optical purities and with the desired configuration. The second goal of the proposal is to demonstrate the synthetic utility of these chiral intermediates. In this context, it is important to mention that intermediates having the sulfonyl and phosphonate groups are well known for their synthetic versatility. It is proposed to develop some new methodology that exploits the unique chemistry of these chiral synthons. More specifically, the intramolecular cyclization reactions of some unsaturated acyl sulfones and acyl phosphonates have much synthetic potential and need to be investigated. Finally, it is proposed to synthesize some known biologically active macrolides such as pyrenophorin and lasiodiplodin using intermediates generated from this work.