Synthesis of Glycoconjugates Containing a 1,2,3-Triazole Unit

Abstract

The glycoconjugates have an enormous potential in drug design1. Between them, glycopeptides are particularly important as they combine the structural features of amino acids and carbohydrates in the same molecule. Glycoconjugates containing the 1,2,3-triazole unit find application in medicinal chemistry, particularly in those cases where this unit acts as a bridge between an amino acid/peptide and the sugar moiety. In this work the synthesis of several glycoconjugates containing the 1,2,3-triazole unit as a bridge between a sugar (D-glucose) moiety and an amino acid or heteroaromatic unit is described. The starting alkynyl esters were prepared by reaction between N-protected glycine, tyrosine and phenylalanine, 7-hydroxycoumarin and 7-hydroxy-4-methylcoumarin and propargyl bromide with high yields. The 1,2,3-triazole unit was formed by an azide-alkyne 1,3-dipolar cycloaddition, catalysed by a Cu(I) species, a chemical process usually known as click chemistry.2,3The azido component was prepared in situ from a-acetobromoglucose. The precursors and the final compounds were characterized by usual methods. Thanks to FCT, Portugal for financial support to the NMR portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho) and to FCT and FEDER -COMPETE-QREN-EU for financial support to the Research Centre, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)]