Total Synthesis of (+)-Azaspiracid-1. An Exhibition of the Intricacies of Complex Molecule Synthesis

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• 作者：David A. Evans ; Lisbet Kvæ ; rnø ; Travis B. Dunn ; André ; Beauchemin ; Brian Raymer ; Jason A. Mulder ; Edward J. Olhava ; Martin Juhl ; Katsuji Kagechika ; David A. Favor
• 刊名：Journal of the American Chemical Society
• 出版年：2008
• 出版时间：December 3, 2008
• 年：2008
• 卷：130
• 期：48
• 页码：16295-16309
• 全文大小：754K
• 年卷期：v.130,no.48(December 3, 2008)
• ISSN：1520-5126

文摘

The synthesis of the marine neurotoxin azaspiracid-1 has been accomplished. The individual fragments were synthesized by catalytic enantioselective processes: A hetero-Diels−Alder reaction to afford the E- and HI-ring fragments, a carbonyl-ene reaction to furnish the CD-ring fragment, and a Mukaiyama aldol reaction to deliver the FG-ring fragment. The subsequent fragment couplings were accomplished by aldol and sulfone anion methodologies. All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. A final fragment coupling of the anomeric EFGHI-sulfone anion to the ABCD-aldehyde completed the convergent synthesis of (+)-azaspiracid-1.