Synthesis of (2S,3S)-2-amino-3-methylpent-4-ynoic acid, a precursor amino acid for the preparation of tritium- or deuterium-labelled peptide in the isoleucine residue

Abstract

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-[²H]lle-Leu. The distribution of deuterium was investigated by fast-atom-bombardment mass spectrometry (FAB-MS) and ¹³C NMR spectroscopy, which confirmed that the deuterium was located entirely at the isoleucine residue.