SYNTHESIS OF ADRIAMYCIN SUGARS AND THIENAMYCIN

阿霉素是蒽环类抗生素家族的一员， 被发现对各种癌症都非常有效。 硫霉素是一种β-内酰胺类抗生素， 它对革兰氏阳性和 革兰氏阴性菌 这些分子中的手性对 在生物活动中的作用。 因此，光学合成 这些化合物的活性形式是重要的。 我们最近开发了 两种制备光学活性分子的新方法：不对称 通过三烷基硼烷的还原，以及在 有机硼酸盐重排的迁移终点。 不对称 炔丙基酮的还原制得基本上光学纯的炔丙基 酒精容易获得，乙炔手柄使酒精 有吸引力的中间体，用于进一步加工。 研究 有机硼烷重排使得光学活性的烯丙基硼烷容易地 第一次接触到。 这些有机硼烷与酮的加成 或醛产生光学活性醇， 手性中心 这些过程将用于一个新的内酯环 膨胀反应，提供了一系列密切相关的手性 可以应用于硫霉素和糖部分的内酯 阿霉素

Adriamycin, a member of the anthracycline family of antibiotics, has been found to be highly effective against a wide variety of cancers. Thienamycin is a Beta-lactam antibiotic isolated from streptomyces cattleya that has shown unusually high potency against both gram-positive and gram-negative bacteria. The chirality in these molecules plays a crucial role in their biological activities. Hence the synthesis of the optically active forms of these compounds is important. We have recently developed two new methods for preparing optically-active molecules: asymmetric reductions via trialkylboranes, and control of stereochemistry at the migration terminus of organoborate rearrangements. The asymmetric reduction of propargyl ketones makes essentially optically-pure propargyl alcohols readily available, and the acetylene handle makes alcohols attractive intermediates for further elaboration. The study of organoborane rearrangements has made optically-active allylboranes readily accessible for the first time. Addition of these organoboranes to a ketone or aldehyde produces optically-active alcohols with several contiguous chiral centers. These processes will be used in a novel lactone ring expansion reaction that provides a series of closely related chiral lactones that can be applied to both thienamycin and the sugar portion of adriamycin.