SYNTHESIS OF [4-CARBORANYLALANINE, 5-LEUCINE]-ENKEPHALIN - (INCLUDING AN IMPROVED PREPARATION OF TERT-BUTOXYCARBONYL-L-ORTHO-CARBORANYLALANINE, NEW DERIVATIVES OF L-PROPARGYLGLYCINE, AND A NOTE ON MELANOTROPIC AND OPIATE RECEPTOR-BINDING CHARACTERISTICS)

The title compound, an analogue of [Leu5]‐enkephalin with L‐o‐carboranylalanine replacing L‐phenylalanine in position 4, was prepared by fragment condensation. The analogue has a 3‐fold higher affinity for rat brain opiate receptors in the [3H]naloxone competition assay than natural [Leu5]‐enkephalin. Like [Leu5]‐enkephalin and Na‐acetyl‐[Leu5]‐enkephalin, the N‐terminal tripeptide fragment, H · Tyr‐Gly‐Gly · OH, had no melanotropic activity in the Rana pipiens frog skin assay. A convenient, direct synthesis of methyl t‐butoxycarbonyl‐L‐propargylglycinate is described, and the 13C‐NMR. spectra of L‐o‐carboranylalanine recorded. The procedure was extended to the preparation of BOC · Car‐Leu · OMe from BOC · Pra‐Leu · OMe. A number of new propargylglycine derivatives are reported. Copyright © 1979 Verlag GmbH & Co. KGaA, Weinheim