SYNTHESIS OF (2S,3S)-2-AMINO-3-METHYLPENT-4-YNOIC ACID, A PRECURSOR AMINO-ACID FOR THE PREPARATION OF TRITIUM-LABELED OR DEUTERIUM-LABELED PEPTIDE IN THE ISOLEUCINE RESIDUE

The synthesis of (2S,3S)-2-amino-3-methylpent-4-ynoic acid (Amp) 1, its incorporation into a peptide chain, and the preparation of a deuterium-labelled peptide in the isoleucine residue are reported. Amino acid 1 was synthesized in three steps from 3-chlorobut-1 -yne. The optical purity of amino acid 1 was determined by HPLC with a chiral stationary-phase column and was found to be more than 99% (ee). Tyr-Amp-Leu was synthesized by solid-phase synthesis based on Fmoc strategy. The tripeptide was deuteriated catalytically to yield Tyr-[H-2]Ile-Leu. The distribution of deuterium was investigated by fast-atom-bombardment mass spectrometry (FAB-MS) and C-13 NMR spectroscopy, which confirmed that the deuterium was located entirely at the isoleucine residue.