A practical synthesis of N-alpha-Fmoc protected L-threo-beta-hydroxyaspartic acid derivatives for coupling via alpha- or beta-carboxylic group

作者：Bionda Nina; Cudic Mare; Barisic Lidija; Stawikowski Maciej; Stawikowska Roma; Binetti Diego; Cudic Predrag^*

来源：Amino Acids, 2012, 42(1): 285-293.

DOI：10.1007/s00726-010-0806-x

• Hydroxyaspartic acid
• Enantioresolution
• Orthogonal protection
• Fmoc solid-phase peptide synthesis

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 (alpha) -Fmoc protected tHyAsp derivatives were prepared ready for couplings via either alpha- or beta-carboxylic group onto the resins or the growing peptide chain. In addition, coupling of tHyAsp via beta-carboxylic group onto amino resins allows preparation of peptides containing tHyAsn sequences, further increasing the synthetic utility of prepared tHyAsp derivatives.

• 出版日期2012-1