SOLUTION SYNTHESIS OF A DIMERIC PENTAPEPTIDE - DIKETOPIPERAZINE CYCLIZATION OF GLU-ASP DIPEPTIDE ESTERS AND ASP-RACEMIZATION DURING SEGMENT CONDENSATION

A haemoregulatory peptide analogue derived from the cystine-dimerised pentapeptide Glp-Glu-Asp-Cys-Lys-OH, in which the cystine residue has been replaced by an isosteric L,L-2,7-diaminosuberic acid moiety, was prepared by segment condensation in solution. The preparation of protected Glp-Glu-Asp-OH tripeptides was found to be hampered by the surprising ease with which t-butyl side-chain protected H-Glu-Asp-OR dipeptide esters underwent diketopiperazine cyclisation. A number of Asp esters were compared in this respect. Reaction conditions for the segment condensation were investigated in terms of racemisation as well as chemical yield and product purity.