Premium
S ‐acyl isopeptide method: Use of allyl‐type protective group for improved preparation of thioester‐containing S ‐acyl isopeptides by Fmoc‐based SPPS
Author(s) -
Yoshiya Taku,
Hasegawa Yuka,
Kawamura Wakana,
Kawashima Hiroyuki,
Sohma Youhei,
Kimura Tooru,
Kiso Yoshiaki
Publication year - 2011
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21410
Subject(s) - chemistry , thioester , acylation , group (periodic table) , combinatorial chemistry , acyl group , protecting group , stereochemistry , organic chemistry , alkyl , enzyme , catalysis
Abstract We have studied the “ S‐ acyl isopeptide method” for the synthesis of peptides containing difficult sequences. The S‐ acyl isopeptide, which contains a β‐thioester instead of the native N‐ acyl bond at a Cys residue, can be converted into the target peptide via an S ‐to‐ N intramolecular acyl migration reaction. However, the synthesis of the S‐ acyl isopeptide structure by Fmoc‐based SPPS is hampered by repetitive base treatments; decomposition of the thioester and the epimerization of the thioesterified residue are commonly observed. Here, we adopted allyloxycarbonyl (Aloc) protective group to avoid the problem. Catalytic amount of Pd in the presence of scavengers such as PhSiH 3 and dimedone selectively removed the Aloc group with neither decomposition of the thioester structure nor epimerization at the thioesterified residue. A model pentapeptide and amylin(1‐12) with difficult sequences were efficiently synthesized by the improved S‐ acyl isopeptides method. Finally, the isolated S‐ acyl isopeptides were quantitatively converted into the desired peptides via the S ‐to‐ N intramolecular acyl migration reaction. The S‐ acyl isopeptide method will be a useful method to prepare the difficult sequence‐containing peptides with Cys residue. © 2010 Wiley Periodicals, Inc.Biopolymers (Pept Sci) 96: 228–239, 2011.