A concise synthesis of isoguanine 2ʹ-deoxyriboside and its adenine-like triplex formation when incorporated into DNA

Abstract

A concise synthesis of 2'-deoxyisoguanosine is achieved whereby 2,6-dichloropurine is glycosylated using the Hoffer sugar to give a pair of beta-configured nucleoside N9/N7 regioisomers that are aminated using methanolic ammonia with concomitant deprotection of the sugar. Following chromatographic separation, pure 2-chloro-2'-deoxyadenosine was isolated as a single isomer. Displacement of the C2 chlorine atom using sodium benzyloxide, followed by hydrogenolysis of the benzyl group, gives 2'-deoxyisoguanosine. Isoguanine was incorporated into DNA by solid supported synthesis using the suitably protected 2-allyloxy-2'deoxyadenosine phosphoramidite with the allyl group being removed post-oligomerisation under Noyori conditions. DNA melting studies showed isoguanine to exhibit adenine-like triplex formation.