Total Synthesis of Phorboxazole A via de Novo Oxazole Formation: Strategy and Component Assembly

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• 作者：Bo Wang ; T. Matthew Hansen ; Ting Wang ; Dimao Wu ; Lynn Weyer ; Lu Ying ; Mary M. Engler ; Melissa Sanville ; Christopher Leitheiser ; Mathias Christmann ; Yingtao Lu ; Jiehao Chen ; Nicholas Zunker ; Russell D. Cink ; Feryan Ahmed ; Chi-Sing Lee ; Craig J. Forsyth
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：February 9, 2011
• 年：2011
• 卷：133
• 期：5
• 页码：1484-1505
• 全文大小：1791K
• 年卷期：v.133,no.5(February 9, 2011)
• ISSN：1520-5126

文摘

The phorboxazole natural products are among the most potent inhibitors of cancer cell division, but they are essentially unavailable from natural sources at present. Laboratory syntheses based upon tri-component fragment coupling strategies have been developed that provide phorboxazole A and analogues in a reliable manner and with unprecedented efficiency. This has been orchestrated to occur via the sequential or simultaneous formation of both of the natural product鈥檚 oxazole moieties from two serine-derived amides, involving oxidation鈭抍yclodehydrations. The optimized preparation of three pre-assembled components, representing carbons 3鈭?7, 18鈭?0, and 31鈭?6, has been developed. This article details the design and syntheses of these three essential building blocks. The convergent coupling approach is designed to facilitate the incorporation of structural changes within each component to generate unnatural analogues, targeting those with enhanced therapeutic potential and efficacy.