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 Zemplé
n transesterification, were regioselectively 3&prime
O-sulfated using tin chemistry activation followed by treatment with sulfur trioxide-trimethylamine complex (Men3N-SO3). Additional derivatives were also prepared from the vanillin&rsquo
s aldehyde using a Knoevenagel reaction to provide extended &alpha
&beta
unsaturated carboxylic acid which was next reduced to the saturated counterpart.