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

Abstract

Abstract A new synthesis is reported for 4‐aminoimidazo[1,2‐ a ]‐1,3,5‐triazin‐2(1 H )‐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(8 H )‐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.