Efficient and Regiospecific Syntheses of Peptides with Piperazic and Dehydropiperazic Acids via a Multicomponent Reaction

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• 作者：Emma L. Handy ; Kyle A. Totaro ; Charlie P. Lin ; Jason K. Sello
• 刊名：Organic Letters
• 出版年：2014
• 出版时间：July 3, 2014
• 年：2014
• 卷：16
• 期：13
• 页码：3488-3491
• 全文大小：278K
• ISSN：1523-7052

文摘

Peptides containing N2-acyl piperazic or 1,6-dehydropiperazic acids can be formed efficiently via a novel multicomponent reaction of 1,4,5,6-tetrahydropyridazines, isocyanides, and carboxylic acids. Remarkably, the reaction鈥檚 induced intramolecularity can enable the regiospecific formation of products with N2-acyl piperazic acid, which counters the intrinsic and troublesome propensity for piperazic acids to react at N1 in acylations. The utility of the methodology is demonstrated in the synthesis of the bicyclic core of the interleukin-1尾 converting enzyme inhibitor, Pralnacasan.