Premium
“Head‐to‐Tail” Cyclization of Hexapeptides Using Different Coupling Reagents
Author(s) -
Zimmer Susanne,
Hoffmann Eike,
Jung Günther,
Kessler Horst
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199319930182
Subject(s) - chemistry , reagent , kinetics , high performance liquid chromatography , combinatorial chemistry , dilution , chromatography , stereochemistry , organic chemistry , physics , quantum mechanics , thermodynamics
In the synthesis of cyclic hexapeptides the cyclization step was examined by using different procedures for activation. Three coupling methods were tested for “head‐to‐tail” cyclization of the resin‐cleaved peptides in solution: (1) DPPA/NaHCO 3 ; (2) TBTU/HOBt/DIEA and (3) HBTU/HOBt/DIEA. The best results were obtained by using TBTU. Reaction rates were 5 to 70 times faster with the TBTU procedure compared to the DPPA activation and generally complete conversions to cyclopeptides were observed. The kinetics of the cyclizations under high dilution conditions were monitored by HPLC. During the synthesis of the linear peptides the formation of an aminosuccinimide was observed. This by‐product was characterized by electrospray MS and NMR.