Macrocycle Synthesis by Chloride-Templated Amide Bond Formation

A new
family of pseudopeptidic macrocyclic compounds has been prepared
involving an anion-templated amide bond formation reaction at the
macrocyclization step. Chloride anion was found to be the most efficient
template in the macrocyclization process, producing improved macrocyclization
yields with regard to the nontemplated reaction. The data suggest
a kinetic effect of the chloride template, providing an appropriate
folded conformation of the open-chain precursor and reducing the energy
barrier for the formation of the macrocyclic product.

本研究合成了一类全新的假肽类大环化合物（pseudopeptidic macrocyclic compounds），其大环化过程采用阴离子模板诱导酰胺键形成的反应策略。研究发现，氯离子（chloride anion）是该大环化反应中最为高效的模板，相较于非模板反应，可显著提升大环化产物的收率。实验数据表明，氯离子模板发挥了动力学效应：它能够使开链前体形成适宜的折叠构象，进而降低大环化产物形成过程中的能垒。