A practical synthesis of N α-Fmoc protected L-threo-ß-hydroxyaspartic acid derivatives for coupling via α- or ß-carboxylic group.

ABSTRACT

A simple and practical general synthetic protocol towards orthogonally protected tHyAsp derivatives fully compatible with Fmoc solid-phase peptide synthetic methodology is reported. Our approach includes enantioresolution of commercially available D ,L -tHyAsp racemic mixture by co-crystallization with L -Lys, followed by ion exchange chromatography yielding enantiomerically pure L -tHyAsp and D -tHyAsp, and their selective orthogonal protection. In this way N ( α )-Fmoc protected tHyAsp derivatives were prepared ready for couplings via either α- or ß-carboxylic group onto the resins or the growing peptide chain. In addition, coupling of tHyAsp via ß-carboxylic group onto amino resins allows preparation of peptides containing tHyAsn sequences, further increasing the synthetic utility of prepared tHyAsp derivatives.