Total Synthesis and Structural Elucidation of Azaspiracid-1. Construction of Key Building Blocks for Originally Proposed Structure

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• 作者：K. C. Nicolaou ; Petri M. Pihko ; Federico Bernal ; Michael O. Frederick ; Wenyuan Qian ; Noriaki Uesaka ; Nicole Diedrichs ; Jü ; rgen Hinrichs ; Theocharis V. Koftis ; Eriketi Loizidou ; Goran Petrovic ; Man
• 刊名：Journal of the American Chemical Society
• 出版年：2006
• 出版时间：February 22, 2006
• 年：2006
• 卷：128
• 期：7
• 页码：2244 - 2257
• 全文大小：453K
• 年卷期：v.128,no.7(February 22, 2006)
• ISSN：1520-5126

文摘

Syntheses of the three key building blocks (65, 98, and 100) required for the total synthesis ofthe proposed structure of azaspiracid-1 (1a) are described. Key steps include a TMSOTf-induced ring-closing cascade to form the ABC rings of tetracycle 65, a neodymium-catalyzed internal aminal formationfor the construction of intermediate 98, and a Nozaki-Hiyama-Kishi coupling to assemble the requiredcarbon chain of fragment 100. The synthesized fragments, obtained stereoselectively in both theirenantiomeric forms, were expected to allow for the construction of all four stereoisomers proposed aspossible structures of azaspiracid-1 (1a-d), thus allowing the determination of both the relative and absolutestereochemistry of the natural product.