The Donor-Acceptor-Acceptor Purine Analog: Transformation of 5-aza-7-deaza-1H-isoguanine (=4-aminoimidazo-[1,2-a]-1,3,5-triazin-2(1H)-one) to 2′-deoxy-5-aza-7-deaza-isoguanosine using purine nucleoside phosphorylase

A new synthesis is reported for 4-aminoimidazo[1,2-a]-1,3,5-triazin-2(1H)-one ( =5-aza-7-deaza-isoguanosine; 8 ), a purine analog that, when incorporated into an oligonucleotide chain, presents a H-bond donor-acceptor-acceptor pattern to a complementary pyrimidine analog. A protected ribose derivative was coupled to 8 to yield 4-amino-8-(β-D -ribofuranosyl)imidazo[1,2-a]-1,3,5-triazin-2(8H)-one ( =5-aza-7-deaza-isoguanosine; 11 ) after deprotection, Alternatively, direct synthesis of both the ribo derivative 11 and the corresponding deoxyribo derivative 17 as the β-D -anomers was achieved using the enzyme purine nucleoside phosphorylase in a one-pot reaction. This adapts a known synthetic approach to yield a new strategy for obtaining diastereoisomerically pure deoxyribonucleoside analogs on 1-gram scales.