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

Abstract

AbstractA 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.