The synthesis of [4-carboranylalanine,5-leucine]-enkephalin

Article abstract of DOI:10.1002/hlca.19790620502

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-o-carboranylalaninate from 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.