Ethyl 2-Cyano-2-(hydroxyimino)acetate (Oxyma): An Efficient and Convenient Additive Used with Tetramethylfluoroformamidinium Hexafluorophosphate (TFFH) to Replace 1-Hydroxybenzotriazole (HOBt) and 1-Hydroxy-7-azabenzotriazole (HOAt) during Peptide Synthesis

The appropriateness of ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma) as a substitute for benzotriazole-based additives, 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. Furthermore, Oxyma suggests a lower risk of explosion than HOBt and HOAt.