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Effect of Residual Water and Microwave Heating on the Half‐Life of the Reagents and Reactive Intermediates in Peptide Synthesis
Author(s) -
Pernille Tofteng A.,
Pedersen Søren L.,
Staerk Dan,
Jensen Knud J.
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201200711
Subject(s) - acylation , peptide synthesis , chemistry , reagent , peptide bond , peptide , microwave heating , microwave , amide , combinatorial chemistry , molecule , organic chemistry , catalysis , biochemistry , physics , quantum mechanics
Precise microwave heating has changed the way many small molecules are being synthesized and, currently, the field of solid‐phase peptide synthesis is undergoing dramatic changes owing to the use of microwave heating. To fully reap the benefits of precise microwave heating for the formation of amide bonds in peptide synthesis, it is important to understand the kinetics of formation and break‐down of activated esters and their N‐acylation of the nascent peptide chain at elevated temperatures. Herein, we present systematic studies of, first, the rate of formation of activated esters by NMR spectroscopy and, second, their N‐acylation during peptide synthesis. A study of the amount of residual water in the solvents revealed a significant effect on electrophilic reagents and intermediates. This observation was expanded into a general study of microwave heating in peptide synthesis.