Synthesis of Galectin Inhibitors by Regioselective 3′-O-Sulfation of Vanillin Lactosides Obtained under Phase Transfer Catalysis

Vanillin-based lactoside derivatives were synthetized using phase-transfer catalyzed reactions from per-O-acetylated lactosyl bromide. The aldehyde group of the vanillin moiety was then modified to generate a series of related analogs having variable functionalities in the para- position of the aromatic residue. The corresponding unprotected lactosides, obtained by Zemplen transesterification, were regioselectively 3 '-O-sulfated using tin chemistry activation followed by treatment with sulfur trioxide-trimethylamine complex (Men(3)N-SO3). Additional derivatives were also prepared from the vanillin's aldehyde using a Knoevenagel reaction to provide extended alpha, beta-unsaturated carboxylic acid which was next reduced to the saturated counterpart.

Automated summary

Vanillin-based lactoside derivatives were synthesized using phase-transfer catalyzed reactions from per-O-acetylated lactosyl bromide. The structure was further modified through various reactions to generate analogs with different functionalities.