ASYMMETRIC SYNTHESIS OF VANCOMYCIN ANTIBIOTICS

万古霉素家族肽类抗生素的第一个成员是 分离于1956年，并且家族的祖先万古霉素已经被 在临床上作为抗生素使用超过25年， 度假村. 这项研究计划的持续目标是开发 有效的方法来合成的主要成员， 万古霉素家族抗生素。 因此，我们将继续 万古霉素和相关同类物伊瑞霉素的实验室合成， ristoclavin、替考拉宁和aridicin A。 联同 执行这些目标，我们将开发新的方法， 复杂氨基酸和细胞周期蛋白肽的不对称合成。在 此外，我们建议开发新的氧化方法， 含酚肽的大环化以形成大环 二苯醚和联苯，万古霉素的关键成分 骷髅 这种方法的成功开发将使 我们追求的生物遗传模拟合成几乎任何成员 万古霉素家族在这个项目的过程中，我们打算 以确认（校正） 这个家庭的主要成员通过全合成。

The first member of the vancomycin family of peptide antibiotics was isolated in 1956, and the progenitor of the family, vancomycin, has been in clinical use for more than twenty-five years as an antibiotic of last resort. The continuing objective of this research program is to develop efficient approaches to the synthesis of the principal members of the vancomycin family of antibiotics. Accordingly, we will pursue laboratory syntheses of vancomycin and the related congeners eremomycin, ristocetin, teicoplanin, and aridicin A. In conjunction with the execution of these objectives, we will develop new methods for the asymmetric synthesis of complex amino acids and cyclin peptides. In addition, we propose to develop new methodology for the oxidative macrocyclization of phenol-containing peptides to form macrocyclic diphenyl ethers and biphenyls, critical constituents of the vancomycin skeleton. The successful development of this methodology will enable us to pursue a biogenetically modeled synthesis of virtually any member of the vancomycin family. During the course of this project we intend to confirm (correct) the absolute stereochemical assignments of the principal members of this family by total synthesis.