文献类型：期刊文献

英文题名：Mechanistic study on the Knorr pyrazole synthesis-thioester generation reaction

作者：Du, Yijun[2];Xu, Yanyan[1];Qi, Chenze[1];Wang, Chen[1]

机构：[1]Shaoxing Univ, Zhejiang Key Lab Alternat Technol Fine Chem Proc, Shaoxing 312000, Peoples R China;[2]Shaoxing Univ, Yuanpei Coll, Shaoxing 312000, Peoples R China

年份：2019

卷号：60

期号：30

起止页码：1999

外文期刊名：TETRAHEDRON LETTERS

收录：SCI-EXPANDED(收录号：WOS:000476965600016)、、Scopus(收录号：2-s2.0-85067864970)、WOS

基金：This research was supported by Zhejiang Provincial Natural Science Foundation of China under Grant No. LY18B020007. All calculations in this study were performed on the supercomputer Center of Shenzhen.

语种：英文

外文关键词：Knorr pyrazole synthesis; Thioester; Native chemical ligation; Mechanism; Theoretical calculations

外文摘要：A novel Fmoc-SPPS compatible peptide thioester generation method leveraging Knorr pyrazole synthesis was reported recently. C-terminal peptide hydrazides, pentane-2,4-dione and excess arylthiol were added in one-pot to efficiently produce peptide thioesters in acidic aqueous solution at room temperature. To elucidate the detailed mechanism of this reaction and the origin of the effect of solution acidity, a theoretical investigation on the Knorr pyrazole synthesis-thioester generation reaction was carried out. Our computational results suggest that the reaction generally proceeds through three stages: hydrazone formation, pyrazole formation and thioester formation. The rate-determining step is the C-O bond cleavage step in the pyrazole formation stage. The formed pyrazole is readily converted to thioester in the presence of excess thiophenol. The effect of solution acidity originates from the need for protonation of oxygen atoms to increase the electrophilicity of carbonyl group or the leaving ability of hydroxyl group. (C) 2019 Elsevier Ltd. All rights reserved.