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Synthesis of peptide thioesters via an N – S acyl shift reaction under mild acidic conditions on an N ‐4,5‐dimethoxy‐2‐mercaptobenzyl auxiliary group
Author(s) -
Nakamura Ken'ichiroh,
Kanao Tomoki,
Uesugi Tomoya,
Hara Toshiaki,
Sato Takeshi,
Kawakami Toru,
Aimoto Saburo
Publication year - 2009
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1164
Subject(s) - thioester , peptide , chemistry , peptide synthesis , moiety , epimer , stereochemistry , residue (chemistry) , combinatorial chemistry , biochemistry , enzyme
Abstract An efficient method of peptide thioester synthesis is described. The reaction is based on an N ‐4,5‐dimethoxy‐2‐mercaptobenzyl (Dmmb) auxiliary‐assisted N ‐ S acyl shift reaction after assembling a peptide chain by Fmoc‐solid phase peptide synthesis. The Dmmb‐assisted N ‐ S acyl shift reaction proceeded efficiently under mildly acidic conditions, and the peptide thioester was obtained by treating the resulting S ‐peptide with sodium 2‐mercaptoethanesulfonate. No detectable epimerization of the amino acid residue adjacent to the thioester moiety in the case of Leu was found. The reactions were also amenable to the on‐resin preparation of peptide thioesters. The utility was demonstrated by the synthesis of a 41‐mer peptide thioester, a phosphorylated peptide thioester and a 33‐mer peptide thioester containing a trimethylated lysine residue. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.