THE SYNTHESIS OF N-BENZYLOXYCARBONYL-L-PROLYL-DEHYDROPHENYLALANYL-L-HISTIDYL-L-LEUCINE

The direct oxidation of a dipeptide azlactone (1) by DDQ affords an optically active unsaturated dipeptide azlactone (2). It was shown that the double bond had the Z-configuration and that no racemization of the proline moiety occurred during the oxidation. The dehydrotripeptide, Z-Pro-ΔPhe-Phe ˙ OH (9b) was prepared by direct coupling of azlactone (2) with phenylalanine tetramethyl-guanidinium salt and was shown to be stable to chymotrypsin. The tetrapeptide, Z-Pro-ΔPhe-His-Leu ˙ OH (11), was prepared directly from the azlactone (2) and by saponification of the tetrapeptide ester (10) prepared by mixed anhydride coupling of Z-Pro-ΔPhe ˙ OH (7) with the dipeptide ester. The dehydropeptide (11) inhibits angiotensin I converting enzyme (IC50, 1 × 10-4 M).