Assessment of racemisation in N-alkylated amino-acid derivatives during peptide coupling in a model dipeptide system

Abstract
N.m.r. analysis of diastereoisomeric benzoyl dipeptide esters has been used to monitor racemisation during the coupling of benzoyl-N-alkylated amino-acids to alanine and valine methyl esters. Results confirm the greater susceptibility of these amino-acids to racemisation, but conditions have been found which eliminate racemisation. The additives HONSu and HOBt vary in their capability as ‘chiral stabilisers’. N.m.r. techniques provide a facile means for monitoring the involvement of oxazolonium ions during coupling. A possible mechanism for racemisation is proposed.