SYNTHESIS AND SEPARATION OF DIASTEREOMERS OF RIBONUCLEOSIDE 5'-(ALPHA-P-BORANO)TRIPHOSPHATES

Nucleoside boranophosphates, in which one of the phosphate oxygens is replaced by a borane group, are isoionic and isoelectronic analogues o f naturally occurring nucleotides. Boranophosphates also are biochemic ally important congeners of phosphorothioates and methylphosphonates. We have developed a convenient one-pot method to synthesize the set of ribonucleoside (A, U, G, and C) 5'-(alpha-P-borano)triphosphates. Pho sphitylation of the 2',3'-protected ribonucleoside with 8-chloro-4H-1, 3,2-benzodioxaphosphorin-4-one gives the 5'-phosphite intermediate 2 w hich undergoes in situ substitution in the presence of pyrophosphate t o give the cyclic intermediate, P-2,P-3-dioxo-P-1-ribonucleosidylcyclo triphosphate 3. Immediate oxidation of compound 3 with amine borane co mplex results in ribonucleoside 5'-(alpha-P-borano)cyclotriphosphate 4 . Subsequent reaction of compound 4 with water followed by ammonium hy droxide yields the crude product as a diastereomeric mixture of ribonu cleoside 5'-(alpha-P-borano)triphosphate 6. Pure compound 6 is isolate d in 30-45% overall yield using ion-exchange chromatography. The separ ation of two diastereomers of ribonucleoside 5'-(alpha-P-borano)tripho sphate 6 is achieved by reverse phase HPLC.