Copper-catalysed C-N/C-O coupling in water: a facile access to N-coumaryl amino acids and fluorescent tyrosine & lysine labels

A mild, efficient, ligand free and environmentally benign approach towards the construction of sp(2) C-sp(3) N bond has been developed via copper catalysed Ullmann type of coupling between 4-chlorocoumarin with N-terminus unprotected amino acids in microwave-aqua conditions, yielding a series of N-coumaryl amino acids in good to excellent yields. Excellent photo-physical properties exhibited by these N-coumaryl amino acids and their chemical applicability as C-terminus coupling partners for N-terminus peptides make them potential fluorescent probes in labelling studies. The methodology was extended towards the C-O and C-N coupling for the synthesis of fluorescent coumaryl labelled tyrosine and lysine labels respectively. Application of coumaryl labelled tyrosine was further explored towards the synthesis of fluorescent labelled opioid tetrapeptide, Endomorphin-2 derivative. (C) 2016 Elsevier Ltd. All rights reserved.