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 一种有效的合成主要成员的方法 万古霉素抗生素家族。因此，我们将致力于 万古霉素苷元及其相关同系物的实验室合成 冬凌草素C、瑞斯托菌素和大蒜素A与 为了实现这些目标，我们将开发新的方法来 复合氨基酸和环肽的不对称合成。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。这种方法的成功发展将使我们能够 以生物遗传模型合成几乎任何一种 万古霉素家族。最后，完整的立体化学赋值 这个抗生素家族的所有成员都依赖于核磁共振波谱，并且 因此，必须被认为是试探性的。在这个过程中 我们打算确认(更正)绝对立体化学的项目 通过全合成对这个家族的主要成员进行的分配。

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 an efficient approach to the synthesis of the principal members of the vancomycin family of antibiotics. Accordingly, we will pursue a laboratory synthesis of vancomycin aglycone and the related congeners orienticin C, ristocetin 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 cyclic 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. Finally, the full stereochemical assignments of all members of this family of antibiotics rests on NMR spectroscopy, and as such must be considered as tentative. 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.