CHIRAL SYNTHONS FOR SYNTHESIS OF BIOLOGICALLY ACTIVE MOLECULES

不对称合成领域的重要性已经增长，这是由于 更加重视评价和销售的活性对映体的 一种与其相应的外消旋体相对的药物。 因此，不对称 各种手性生物活性分子的合成方法 以及它们的结构类似物是化学家非常感兴趣的 和制药业。 PI研究项目的目标是 开发新的和有用的方法学为不对称合成的一个 各种生物活性分子。 这项提案的第一个目标是 是开发用于制备许多功能化的 手性非外消旋羟基砜和羟基膦酸酯。 面包酵母 适当的羰基前体或脂肪酶催化的还原 外消旋醇的拆分都将被仔细检查， 这些手性配体在高浓度下产生的可能途径 光学纯度和所需的配置。 的第二个目标 该建议是为了证明这些手性化合物的合成效用， 中间体的 在这方面，必须指出， 具有磺酰基和膦酸酯基团的中间体是公知的 因为它们的合成多功能性。 建议开发一些新的 该方法利用了这些手性双光子的独特化学性质。 更具体地说，一些化合物的分子内环化反应可以通过以下方式进行： 不饱和酰基砜和酰基膦酸酯具有许多合成 有潜力，需要研究。 最后，建议 合成一些已知具有生物活性大环内酯类化合物 和毛双碘吡啶的方法。

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.