Handy Emma L, Totaro Kyle A, Lin Charlie P, Sello Jason K
Department of Chemistry, Brown University , 324 Brook Street, Providence, Rhode Island 02912, United States.
Org Lett. 2014 Jul 3;16(13):3488-91. doi: 10.1021/ol501425b. Epub 2014 Jun 17.
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's 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-1β converting enzyme inhibitor, Pralnacasan.
含有N2-酰基哌嗪酸或1,6-脱氢哌嗪酸的肽可以通过1,4,5,6-四氢哒嗪、异腈和羧酸的新型多组分反应高效形成。值得注意的是，该反应诱导的分子内性能够实现具有N2-酰基哌嗪酸的产物的区域特异性形成，这与哌嗪酸在酰化反应中在N1处反应的固有且麻烦的倾向相反。该方法的实用性在白细胞介素-1β转化酶抑制剂普拉那卡森的双环核心合成中得到了证明。
