SYNTHESIS OF AMINO-ACID DERIVATIVES SUBSTITUTED IN THE BACKBONE WITH STABLE ISOTOPES FOR APPLICATION IN PEPTIDE-SYNTHESIS

Starting from the corresponding precursors, 1 and 2, the two well know n procedures for asymmetric synthesis of amino acids, those of Schollk opf and Oppolzer, were compared for the preparation of [1,2-C-13(2),N- 15]-labelled (substituted) Boc-leucine enantiomers. Although both gave the final products in comparable overall yields, analysis of optical purity by two independent chromatographic methods revealed that the tw o procedures differed considerably in this respect. The enantiomeric e xcess found was 97.2-97.4 and 99.7%, respectively. As a consequence, t he latter method was preferred for the synthesis of a number of additi onal backbone-labelled Boc-derivatives of the three proteinogenic amin o acids alanine, phenylalanine and tyrosine, including such deuteriate d in the amino acid side-chain. These derivatives exemplify precursors suitable for chemical synthesis of specifically backbone-labelled pep tides and should allow greater exploitation of the properties of the C -13 and, especially, the N-15 nuclei in structural studies.