Synthesis of free and Nalpha-Fmoc/Ngamma-Boc protected (2S, 4S)- and (2S, 4R)-4-aminopipecolic acids

The preparation of (2S,4S)- and (2S,4R)-4-aminopipecolic acid, a conformationally constrained basic amino acid bearing orthogonal Nα/Nγ-protection suitable for solid-phase peptide synthesis, is reported. These amino acids were synthesised from enantiopure ethyl (2S)-4-oxo-1-(1-phenylethyl)- piperidine-2-carboxylate (1) with introduction of the side-chain amino group by reductive amination, followed by protection/ deprotection of the functional groups. A mixture of Fmoc-Sly(Boc)-OH 6 and 7 was used to establish their compatibility in solid-phase peptide synthesis.