Solid-Phase Syntheses of Glu20Ala20Phe and Ala20Glu20Phe by the Step-by-step Coupling of Dipeptide and Tetrapeptide

Glu20Ala20Phe, (I), and Ala20Glu20Phe, (II), were synthesized by the step-by-step coupling of Nα-t-butoxycarbonyl (BOC-) derivatives of Ala–Ala and (γ-benzyl–Glu)4 to phenylalanyl-1% crosslinked polystyrene resin using dicyclohexylcarbodiimide. The products were cleaved from the resin with hydrogen bromide in acetic acid and purified by gel filtration, followed by DEAE-cellulose chromatography, with yields of approximately 10% for both of the hentetracontapeptides. The optical purities of the glutamic acid and alanine incorporated in the pep tides, I and II, were estimated as 1 and 5% respectively from the analysis of the diastereomeric mixture of dipeptides derived from the reaction between the total acid hydrolyzate of I or II with the N-hydroxysucinimidyl ester of BOC–l-Leu.