Synthesis of Dragmacidin D via Direct C鈥揌 Couplings

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• 作者：Debashis Mandal ; Atsushi D. Yamaguchi ; Junichiro Yamaguchi ; Kenichiro Itami
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：December 14, 2011
• 年：2011
• 卷：133
• 期：49
• 页码：19660-19663
• 全文大小：819K
• 年卷期：v.133,no.49(December 14, 2011)
• ISSN：1520-5126

文摘

Dragmacidin D, an emerging biologically active marine natural product, has attracted attention as a lead compound for treating Parkinson鈥檚 and Alzheimer鈥檚 diseases. Prominent structural features of this compound are the two indole鈥損yrazinone bonds and the presence of a polar aminoimidazole unit. We have established a concise total synthesis of dragmacidin D using direct C鈥揌 coupling reactions. Methodological developments include (i) Pd-catalyzed thiophene鈥搃ndole C鈥揌/C鈥揑 coupling, (ii) Pd-catalyzed indole鈥損yrazine N-oxide C鈥揌/C鈥揌 coupling, and (iii) acid-catalyzed indole鈥損yrazinone C鈥揌/C鈥揌 coupling. These regioselective catalytic C鈥揌 couplings enabled us to rapidly assemble simple building blocks to construct the core structure of dragmacidin D in a step-economical fashion.