Among active site directed inhibitors of HIV reverse transcriptase are the "natural" dideoxynucleosides: 2',3'-dideoxyadenosine (ddA) and its metabolite, 2',3'-dideoxyinosine (ddl), 2',3'-dideoxyguanosine (ddG), and 2',3'-dideoxycytidine (ddC).1-5 However, dideoxynucleosides, particularly those of the purine family, are inherently unstable with respect to cleavage of the glycosidic bond,2 3456•7 ***because of the absence of the -I effect of the OH groups and the involvement in hydrolysis of the proximal ring oxygen. The discovery of therapeutically useful antiviral com-

A new method is reported for the synthesis of oligodeoxyribonucleotides containing 2-aminopurine residues at selected sites. This method involves protection of the 2-aminopurine ribonucleoside, reduction to the deoxyribonucleoside and standard preparation of the 5'-0- (4,4'-dimethoxytrityl)-3'-O-(2-cyanoethyl)-N,N- diisopropylphosphoramidite. The 2-aminopurine phosphoramidite prepared by this method couples with high efficiency and is stable under standard automated synthesis conditions. The presence and location of the 2-aminopurine residue is easily verified by treatment of the oligodeoxyribonucleotide with hot piperidine. The mechanism for selective hydrolysis of the 2-aminopurine residue in alkaline solution is predominantly direct cleave of the glycosidic bond.

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