2-Cyano-2-(hydroxyimino)acetate (Oxyma): An Efficient reagent for coupling of N-protected amino acids
Sherine N. Khattab
Department of Chemistry, Faculty of Science,
University of Alexandria,
Alexandria 21321, Egypt
Abstract:
Peptide synthesis is based on the proper combination of protecting groups and in the right choice of coupling method.1 Preventing the loss of configuration is one of the major challenges in peptide synthesis.2,3 The appropriateness of ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma) as a substitute for the benzotriazole-based additives,4 the most used additives nowadays, for use in the TFFH approach for peptide synthesis, is discussed in terms of its capacity to control racemization, its coupling efficiency in difficult couplings either for stepwise or segment coupling in solution and solid phase coupling. In addition, Boc-based solution phase peptide synthesis and its stability in the presence of growing peptide chains were studied. Oxyma displayed remarkable results in terms of racemization depression together with impressive coupling efficiency in both solution and solid phase synthesis.
In addition, a new family of sulfonate ester-type coupling reagents is described which differs in its leaving group. The oxyma sulfonate ester coupling reagents ethyl 2-cyano-2-(naphthalen-2-ylsulfonyloxyimino) acetate (NpsOXY), and ethyl 2-cyano-2-(tosyloxyimino)acetate (TsOXY) are more efficient alternatives to the benzotriazole sulfonate esters5 in terms of racemization suppression and coupling effectiveness. An improvement in yield and almost comparable optical purity to that of the HOBt and HOAt analogues was observed. Both Oxyma and its related sulfonate esters can be handled with a considerably lower risk than the explosive benzotriazole and its derivatives.
References:
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