Effect of copper(II) chloride on suppression of racemization in peptide synthesis by the carbodiimide method.
Copper(II) chloride was found to be an extremely efficient racemization-suppressing additive in the DCC method as compared with the hitherto known ones, by employing the model coupling Z-Gly-L-Val-OH + H-L-Val-OMe in DMF. Although some other copper salts also had a profound effect, copper(II) chloride was the best from the viewpoint of both racemization suppression and coupling efficiency. The effectiveness of copper(II) chloride was further confirmed by employing the EDC-mediated couplings of Z-Gly-containing dipeptides with amino acid esters or dipeptide esters, and those of Z-L-Ala (or L-Val)-L-Val-OH with amino acid esters or dipeptide esters. In almost all the cases studied, no detectable amount (less than 0.1%) of epimer was observed by the HPLC analysis in the presence of copper(II) chloride. This was also the case even with an extremely stringent coupling system Z-L-Pro-L-Val-OH + H-L-Pro-OMe. With reference to the mechanism of racemization suppression, it was found that copper(II) chloride has a strong ability to suppress the racemization of the 5(4H)-oxazolone, which may be formed from an activated carboxyl component during the coupling.
Miyazawa
T
T
Department of Chemistry, Faculty of Science, Konan University, Kobe, Japan.
Otomatsu
T
T
Fukui
Y
Y
Yamada
T
T
Kuwata
S
S
D000595:Amino Acid Sequence; D002234:Carbodiimides; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000494:pharmacology*; D004024:Dicyclohexylcarbodiimide; D004126:Dimethylformamide; D005022:Ethyldimethylaminopropyl Carbodiimide; D007536:Isomerism; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
D002234:Carbodiimides; D010455:Peptides; D004024:Dicyclohexylcarbodiimide; D003300:Copper; D004126:Dimethylformamide; D005022:Ethyldimethylaminopropyl Carbodiimide; C029892:cupric chloride