Synthesis of a boron analogue of glucose-conjugated nucleoside diphosphate: nucleoside α-P-boranodiphosphoglucose

Analogues of nucleoside diphosphohexoses are useful for investigating the role of nucleotidyl sugars in oligosaccharide metabolism. Here, adenosine α-P-boranodiphosphoglucose 4, a boron analogue of ADP-glucose in which borane (BH3) replaces the non-bridging oxygen of the phosphate, was prepared in good yield. The two diastereomers (4a and 4b) were successfully separated by reverse phase HPLC, and the chemical structures of isomers 4a and 4b were established via spectroscopic methods. The analogue may be useful for investigations of the stereochemistry and mechanism of enzymes such as glycogen and starch synthetases, glycosidyl and nucleosidyl transferases, kinases, etc. The described method may be used to prepare other boronated nucleotidyl sugar analogues for potential therapeutic applications and delivery of boron into cells for boron neutron capture therapy.