The Synthesis of [4‐Carboranylalanine, 5‐Leucine]‐Enkephalin (Including an Improved Preparation of t ‐Butoxycarbonyl‐ L ‐ o ‐carboranylalnine, New Derivatives of L ‐Propargylglycine, and a Note on Melanotropic and Opiate Receptor Binding Characteristics)

The title compound, an analogue of [Leu 5 ]‐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 [ 3 H]naloxone competition assay than natural [Leu 5 ]‐enkephalin. Like [Leu 5 ]‐enkephalin and N a ‐acetyl‐[Leu 5 ]‐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 13 C‐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.