Electrochemical synthesis of C-glycosides as non-natural mimetics of biologically active oligosaccharides

Abstract

Natural oligosaccharides inhibitors of heparanase and selectins are emerging as promising drugs for cancer therapy. As an alternative tool to the natural ones, sulfated tri maltose C-C-linked dimers (alfa,alfa alfa,beta and beta,beta STMCs) were prepared by bromo-maltotriose electroreduction on silver cathode,1 followed by sulfation. The presence of an interglycosidic C-C bond makes STMCs less vulnerable to metabolic processing then their O-analogues. For this reason, STMCs have been studied as drug candidates and inhibitors of carbohydrate processing enzymes. Their activity as inhibitor of Pselectin in vivo and in the attenuation of metastasis both on B16-BL6 melanoma cells and on MC- 38 carcinoma cells2 prompted to the optimization of their synthetic process. Therefore, the electrochemical process for the C-C coupling of the model molecule acetobromoglucose has been investigated by changing various reaction conditions such as solvent and arrangement of the electrolytic cell, aiming at the final scale-up of the reaction.