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Application of Pac Ester in Thioester Method for the Synthesis of Cyclopentapeptides
Author(s) -
Liu Mian,
Tian GuiLing,
Ye YunHua
Publication year - 2003
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.20030210729
Subject(s) - chemistry , thioester , pentapeptide repeat , trifluoroacetic acid , acetic acid , peptide synthesis , peptide , combinatorial chemistry , organic chemistry , stereochemistry , biochemistry , enzyme
Thioester method for the synthesis of cyclopeptides is improved by using Pac (Pac = phenacyl, CH 2 COC 6 H 5 ) ester as a protecting group of 3‐mercaptopropionic acid. The Pac group is easy to be removed from C ‐terminal with zinc in acetic acid. The protected glycine thioester and peptide thioesters synthesized by the improved method, are easy to be purified, so the final linear peptides are pure enough for the following cyclization. Furthermore, this method is flexible for peptide chain elongation, either from C‐terminal or from N ‐terminal. So it is an efficient and practical method for synthesis of bioactive peptides. Two N ‐protected pentapeptide thioesters, Boc‐Pro‐Tyr‐Leu‐Ala‐GlySCH 2 CH 2 COOPac and Boc‐Ala‐Tyr‐Leu‐Ala‐Gly‐SCH 2 CH 2 ‐COOPac were synthesized by the improved thioester method. After deprotecting Pac ester with zinc in aqueous acetic acid and Boc group with trifluoroacetic acid in CH 2 Cl 2 , two free pentapeptide thioesters were obtained. Ag + ‐assisted cyclization in acetate buffered solution afforded two cyclic pentapeptides c(Pro‐Tyr‐Leu‐Ala‐Gly) and c(Ala‐Tyr‐Leu‐Ala‐Gly). Effects of different buffer pH, different Ag + concentrations, etc. on the cyclization were studied.