Synthesis of Free and N-alpha-Fmoc-/N-gamma-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 N?/N?-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.