Catalytic Site-Selective Thiocarbonylations and Deoxygenations of Vancomycin Reveal Hydroxyl-Dependent Conformational Effects

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• 作者：Brandon S. Fowler ; Kai M. Laemmerhold ; Scott J. Miller
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：June 13, 2012
• 年：2012
• 卷：134
• 期：23
• 页码：9755-9761
• 全文大小：559K
• 年卷期：v.134,no.23(June 13, 2012)
• ISSN：1520-5126

文摘

We have examined peptide-based catalysts for the site-selective thiocarbonylation of a protected form of vancomycin. Several catalysts were identified that either enhanced or altered the inherent selectivity profile exhibited by the substrate. Two catalysts, one identified through screening and another through rational design, were demonstrated to be effective on 0.50-g scale. Deoxygenations led ultimately to two new deoxy-vancomycin derivatives, and surprising conformational consequences of deoxygenation were revealed for one of the new compounds. These effects were mirrored in the biological activities of the new analogues and support a structural role for certain hydroxyls in the native structure.