PREPARATION AND PROPERTIES OF N(ALPHA)DI-TERT-BUTOXYCARBONYL AMINO-ACIDS - APPLICABILITY IN THE SYNTHESIS OF LEU-ENKEPHALIN

The synthesis of Na-di-tert-butoxycarbonyl amino acids starting from the corresponding mono-derivatives via a three-step route is reported. The latter were converted into a suitable ester and then exhaustively t-butoxycarbonylated, after which the ester was selectively cleaved. The intermediates and products are characterised together with some active esters. The Boc2-amino acids are stable, crystalline compounds which can be used for coupling in peptide synthesis. They react more slowly than the corresponding Boc-amino acids owing to steric hindrance. Their applicability in peptide synthesis is demonstrated in the synthesis of Leu-enkephalin. In the coupling of Boc2-Tyr(Bzl)-ONp to Gly-Gly-Phe-Leu-OBzl, a large amount of a hydantoin derivative was obtained as a by-product. Some factors influencing the formation of hydantoins were studied. Boc2-amino acids seem to enhance the risk of formation of such compounds in comparison with the ordinary monosubstituted amino acids.