Triazole groups as biomimetic amide groups in peptides can trigger racemization

Amino acids are key building blocks for the synthesis of chiral organic materials. In this context, alpha-azido amino acids are interesting starting materials which allow the construction of functionalized, amino-acid based compounds by copper-catalyzed alkyne-azide click reactions. We have now employed this strategy for the synthesis of arginine-derivatives and found that the formation of the azide and the click reaction can be carried out in good yields and with almost no loss of stereopurity. However, further transformation by saponification/amide-formation led to significant racemization at the alpha-carbon. This process was investigated in detail, showing that the triazole-moiety seems to be responsible for the facile racemization. Thus, the highly useful modification of alpha-azido amino acids by the CuAAC-reaction needs to be used with caution when stereopure materials are desired. [GRAPHICS]

Automated summary

The synthesis of arginine-derivatives using copper-catalyzed alkyne-azide click reactions has been studied. While it allows for good yields with almost no loss of stereopurity, further transformation may lead to racemization at the alpha-carbon. Caution is advised when using this highly useful modification strategy for alpha-azido amino acids.