Scalable Total Synthesis and Biological Evaluation of Haouamine A and Its Atropisomer

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• 作者：Noah Z. Burns ; Irina N. Krylova ; Rami N. Hannoush ; Phil S. Baran
• 刊名：Journal of the American Chemical Society
• 出版年：2009
• 出版时间：July 8, 2009
• 年：2009
• 卷：131
• 期：26
• 页码：9172-9173
• 全文大小：183K
• 年卷期：v.131,no.26(July 8, 2009)
• ISSN：1520-5126

文摘

A total synthesis of the complex, bent aromatic ring-containing marine alkaloid haouamine A is achieved through a route in which every step (with the exception of the final deprotection) is performed on a gram-scale. This is accomplished through the development of a method for the dehydrogenation of cyclohexenones that allows for point-to-planar chirality transfer. This strategy makes it possible to program the desired atropisomeric outcome from a simple chiral cyclohexenone. By synthesizing atrop-haouamine A, this work has firmly established that natural haouamine exists as a single, nonequilibrating atropisomer. Finally, biological investigations demonstrate that the bent aromatic ring of this natural product is critical for anticancer activity against PC3 cells.