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 alpha-phosphorus replaced by a borane (BH3) group, has shown potential applications in DNA sequencing. We have developed a convenient method for the syn thesis of the 2'-deoxy-5'-(alpha-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 siru reaction of 2 with pyrophosphate leads to P-2,P-3-dioxo-P-1-(2'-deoxyribonucleosidyl-5'-)cyclptriphosphite (3). Subsequent reaction of 3 with N,N-diisopropylethylamine-borane complex yields P-1-borano-(2'-deoxyribonucleosidyl-5')cyclotriphosphate (4), which upon hydrolysis under mild conditions gives the base/sugar protected 2'-deoxyribonucleoside-5'-(alpha-P-borano)triphosphate (5). Treatment of 5 with ammonia:methanol (2:1 v/v) yields the diastereoisomeric mixture of 2'-deoxyribonucleoside-5'-(alpha-P-borano)triphosphate (6). Separation of the two diastereoisomers of 6 is performed by reverse phase HPLC. (C) 1998 Elsevier Science Ltd. All rights reserved.