ASYMMETRIC SYNTHESIS OF VANCOMYCIN ANTIBIOTICS

万古霉素多肽抗生素家族的第一个成员是 1956年被隔离，家族的祖先万古霉素一直是 作为一种抗生素在临床上使用了25年以上 度假村。这项研究计划的持续目标是开发 有效地合成主要成员的方法 万古霉素抗生素家族。因此，我们将继续 万古霉素及其相关同系物埃雷霉素的实验室合成， 瑞斯托菌素、替考拉宁和大蒜素A联合 为了实现这些目标，我们将开发新的方法来 复合氨基酸和细胞周期蛋白多肽的不对称合成。在……里面 此外，我们还建议开发新的氧化方法。 含酚多肽的大环化反应生成大环 万古霉素的关键成分--二苯醚和联苯 骷髅。这一方法的成功开发将使 美国将对几乎任何成员进行生物遗传模拟合成 属于万古霉素家族。在这个项目的过程中，我们打算 确认(纠正)绝对的立体化学指定 这个家族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.