Total Synthesis of Daptomycin by Cyclization via a Chemoselective Serine Ligation

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• 作者：Hiu Yung Lam ; Yinfeng Zhang ; Han Liu ; Jianchao Xu ; Clarence T. T. Wong ; Ci Xu ; Xuechen Li
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：April 24, 2013
• 年：2013
• 卷：135
• 期：16
• 页码：6272-6279
• 全文大小：480K
• 年卷期：v.135,no.16(April 24, 2013)
• ISSN：1520-5126

文摘

A total synthesis of daptomycin, the first natural product antibiotic launched in a generation, was achieved. This convergent synthesis relies on an efficient macrocyclization via a serine ligation to assemble the 31-membered cyclic depsipeptide. The difficult esterification by the nonproteinogenic amino acid kynurenine was accomplished via the esterification of a threonine residue by a suitably protected Trp ester, followed by ozonolysis. This synthesis provides a foundation and framework to prepare varied analogues of daptomycin to establish its structure鈥揳ctivity profile.