Synthesis of boron-containing ADP and GDP analogues: Nucleoside 5'-(Pα- boranodiphosphates)

New 5'-(Pα-boronated) analogues of the naturally occurring nucleoside diphosphates ADP and GDP were synthesized in good yields, i.e., adenosine 5'- (Pα-boranodiphosphate) (ADPαB; 5a) and guanosine 5'-(Pα-boranodiphosphate) (GDPαB; 5b). Their diastereoisomers were successfully separated by reversed- phase HPLC, and chemical structures were established via spectroscopic methods. The isoelectronic substitution of borane (BH3) for one of the non- bridging O-atoms in phosphate diesters should impart an increase in lipophilicity and change in polarity in ADPαB and GDPαB. The boronated nucleoside diphosphates could be employed for investigations of the stereochemical course and metal requirements of enzymatic reactions involving ADP and GDP, and as carriers of ¹⁰B in boron neutron-capture therapy (BNCT) for the treatment of cancer.

Duke Scholars

Author Barbara R. Shaw Chemistry