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

Nina Bionda, Maré Cudic, Lidija Barisic, Maciej Stawikowski, Roma Stawikowska, Diego Binetti, Predrag Cudic

Index: Amino Acids 42(1) , 285-93, (2012)

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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 β-carboxylic group onto the resins or the growing peptide chain. In addition, coupling of tHyAsp via β-carboxylic group onto amino resins allows preparation of peptides containing tHyAsn sequences, further increasing the synthetic utility of prepared tHyAsp derivatives.