D-glucose- and D-mannose-based antimetabolites. Part 2. Facile synthesis of 2-deoxy-2-halo-D-glucoses and -D-mannoses.

Modified D-glucose and D-mannose analogs are potentially clinically useful metabolic inhibitors. Biological evaluation of 2-deoxy-2-halo analogs has been impaired by limited availability and lack of efficient methods for their preparation. We have developed practical synthetic approaches to 2-deoxy-2-fluoro-, 2-chloro-2-deoxy-, 2-bromo-2-deoxy-, and 2-deoxy-2-iodo derivatives of D-glucose and D-mannose that exploit electrophilic addition reactions to a commercially available 3,4,6-tri-O-acetyl-D-glucal.