SYNTHESIS AND BIOLOGICAL EVALUATION OF 2'-DEOXYRIBONUCLEOTIDE ANALOGS

Two new methods for the synthesis of 2'-deoxyribonucleosides have been developed. The first involves regioselective reductive deoxygenation of a suitably derivatized ribonucleoside. Tri-n-butyltin hydride reduction of a 2'-thiobenzoate derivative affords the desired 2'-deoxyribonucleoside in good yield. The second method for 2'-deoxyribonucleoside synthesis involves the stereoselective coupling of a derivatized 2-deoxyribofuranosyl bromide with heterocycles in the presence of silver tetrafluoroborate. These methods have been applied to the synthesis of 2'-deoxy-lin-benzoadenosine, a fluorescent deoxyribonucleotide analog. The analog was converted into the corresponding 5'-mono-, di-, and triphosphate derivatives. The diphosphate was found to be a substrate for phosphorylation by pyruvate kinase, and the triphosphate was found to be an acceptable replacement for 2'-deoxyadenosine-5'-triphosphate in DNA nick translation by E. coli DNA polymerase I.