An Efficient Synthesis Of Acyclic N 7 - and N 9 -Adenine Nucleosides Via Alkylation With Secondary Carbon Electrophiles to Introduce Versatile Functional Groups At the C-1 Position of Acyclic Moiety

The introduction of versatile functional groups, allyl and ester, at the C-1 position of the acyclic chain in acyclic adenine nucleosides was achieved for the first time directly by alkylation of adenine and N-6-protected adenine. Thus, the C-1'-substituted N-9-adenine acyclic nucleoside, adenine-9-yl-pent-4-enoic acid ethyl ester (11), was prepared by direct alkylation of adenine with 2- bromopent-4-enoic acid ethyl ester (6), while the corresponding N-7-regioisomer, 2-[6, (dimethylaminomethyleneamino)-purin-7-yl]-pent-4-enoic acid ethyl ester (10), was obtained in one step by the coupling of N,N-dimethyl-N'- (9H-purin-6-yl)-formamidine (9) with 2-bromopent-4-enoic acid ethyl ester (6). The functional groups, ester and allyl, were converted to the desired hydroxymethyl and hydroxyethyl groups, and subsequently to phosphonomethyl derivatives and corresponding pyrophosphorylphosphonates.