The synthesis of N-benzyloxycarbonl-L-prolyl-dehydrophenylalanyl-L-histidyl-L-leucine: a converting-enzyme inhibitor.
The direct oxidation of a dipeptide azlactone (1) by DDG 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-delta-Phe-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-delta-Phe-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-deltaPhe  OH (7) with the dipeptide ester. The dehydropeptide (11) inhibits angiotensin I converting enzyme (IC50, 1X10-4 M).
D000806:Angiotensin-Converting Enzyme Inhibitors; D055598:Chemical Phenomena; D002621:Chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D009842:Oligopeptides