Total Synthesis of Lepadiformine Alkaloids using N-Boc 伪-Amino Nitriles as Trianion Synthons

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• 作者：Matthew A. Perry ; Matthew D. Morin ; Brian W. Slafer ; Scott D. Rychnovsky
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：April 6, 2012
• 年：2012
• 卷：77
• 期：7
• 页码：3390-3400
• 全文大小：485K
• 年卷期：v.77,no.7(April 6, 2012)
• ISSN：1520-6904

文摘

Lepadiformine A, B, and C were synthesized in an enantiomerically pure form using a reductive cyclization strategy. N-Boc 伪-amino nitriles were deprotonated and alkylated with enantiomerically pure dibromides to afford the first ring. The products were manipulated to introduce phosphate leaving groups, and subsequent reductive lithiation followed by intramolecular alkylation formed the second ring with high stereoselectivity. The third ring was formed by intramolecular displacement of a mesylate by the deprotected amine. Lepadiformine A and B contain a hydroxymethyl group adjacent to the amine. This appendage was introduced in a sequence using a Polonovski鈥揚otier reaction as the key step. The synthetic strategy is stereoselective and convergent and demonstrates the utility of N-Boc 伪-amino nitriles as linchpins for alkaloid synthesis.