Abstract
The use of N-carboxymethyl amino acids in the assembly of peptides with backbone cyclization can lead to diketopiperazine formation by intramolecular aminolysis which occurs despite the tert-butyl protection of the carboxy group. This undesired side reaction can be prevented by a very short deprotection time for the Fmoc group, by elongation of the N-carboxyalkyl chain or by forming the backbone (lactam) bridge before Fmoc removal, but not by the use of DBU or additives.
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Besser, D., Greiner, G. & Reissmann, S. Side Reaction with N-Carboxymethyl Amino Acids in the Synthesis of Backbone Cyclized Peptides. Letters in Peptide Science 5, 299–303 (1998). https://doi.org/10.1023/A:1008806304435
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DOI: https://doi.org/10.1023/A:1008806304435