Synthesis and evaluation of iminocoumaryl and coumaryl derivatized glycosides as galectin antagonists

A collection of iminocoumarylmethyl glycoside derivatives have been prepared by copper-catalyzed multi-component reaction of carbohydrate propargyl derivatives, sulfonyl azides, and salicylaldehyde or o-hydroxy acetophenone. The method is simple, versatile to all three components, and exceptionally high yielding. The carbohydrate N-sulfonyl iminocoumarine hybrid molecules were evaluated for binding galectin-1, -2, -3, -4 N, -4C, -7, -8 N, -9 N, and 9C using a competitive fluorescence polarization assay. Selective compounds were identified against galectin-3, 7, 8 N, and 9 N with up to 40-fold affinity enhancements relative to methyl α-d-galactopyranoside due to the coumarylmethyl moieties.