Stereoselective approaches toward the synthesis of nucleoside antibiotic core aminoribosyl glycyluridine

Antibiotics that have a novel mechanism of action are urgently required for treatment of drug-resistant microorganisms. Naturally occurring nucleoside antibiotics have shown promising antibacterial activity by inhibiting bacterial translocase MraY, a key enzyme involved in catalysis of the first step of bacterial peptidoglycan biosynthesis. Despite having promising antibiotic properties, a major challenge toward development of this important class of compounds as drug candidates is their complex multistep synthesis. Specifically, efficient synthetic methodologies toward producing the aminoribosylated uridine-derived core unit in a stereo-controlled manner is seen as an essential prerequisite for detailed structure-activity relationship (SAR) studies. This review summarizes approaches available for the stereoselective synthesis of nucleoside core pharmacophores, including both 5′-C-glycyluridine (GlyU) as well as it's β-selective ribosylation.