A convenient synthesis of 2'-deoxyribonucleoside 5'-(α-P- borano)triphosphates

A new class of nucleotides, with one of the two non-bridging oxygens at α-phosphorus replaced by a borane (BH3) group, has shown potential applications in DNA sequencing. We have developed a convenient method for the synthesis of the 2'-deoxy-5'-(α-P-borano)triphosphates of adenosine, guanosine, cytidine, thymidine and uridine (6a-e) that is time and cost effective compared to the previously reported method. The appropriate base/sugar protected nucleoside 1 is phosphitylated with 2-chloro-4H-1,3,2- benzodioxaphosphorin-4-one to give the corresponding cyclic intermediate, 2- (2'-deoxyribonucleosidyl-5'-O-)-4H-1,3,2-benzodioxaphosphorin-4-one (2). The in situ reaction of 2 with pyrophosphate leads to P²,P³-dioxo-P¹-(2'- deoxyribonucleosidyl-5')cyclotriphosphite (3). Subsequent reaction of 3 with N,N-diisopropylethylamine-borane complex yields P¹-borano-(2'- deoxyribonucleosidyl-5')cyclotriphosphate (4), which upon hydrolysis under mild conditions gives the base/sugar protected 2'-deoxyribonucleoside-5'- (α-P-borano)triphosphate (5). Treatment of 5 with ammonia:methanol (2:1 v/v) yields the diastereoisomeric mixture of 2'-deoxyribonucleoside-5'-(α-P- borano)triphosphate (6). Separation of the two diastereoisomers of 6 is performed by reverse phase HPLC.

Duke Scholars

Author Barbara R. Shaw Chemistry