Synthesis of 6-Thioguanine and 2, 6-Diaminopurine Nucleosides and Nucleotides from Adenine Counterparts via a Facile Rearrangement in the Base Portion (Nucleosides and Nucleotides. XIX)

Abstract

A method of conversion of an adenine moiety to 6-thioguanine (and guanine) and 2, 6-diaminopurine moiety in the nucleoside and nucleotide levels were presented. The action of cyanogen bromide with adenosine N¹-oxide afforded an 1, 2, 4-oxadiazolo (3, 2-f)-purine riboside (2a), which was in a pH dependent equilibrium with N⁶-cyanoadenosine N¹-oxide (3a). Methylation followed by alkaline treatment of 3a resulted in a rearrangement leading to give 2-amino-N⁶-methoxyadenosine (5a). Catalytic hydrogenation of 5a gave 2, 6-diaminopurine riboside (6a). Sulfhydrolysis of 5a gave 6-thioguanosine (7a). By a similar reaction sequence 2'-deoxyadenosine was converted to 2'-deoxy-6-thioguanosine (7b) and 2, 6-diaminopurine 2'-deoxyriboside, respectively. Starting from the N¹-oxides of adenosine 5'-phosphate (AMP), 2'-deoxyadenosine 5'-phosphate (dAMP) and 9-β-D-arabinofuranosyladenine 5'-phosphate (araAMP), the corresponding 6-thioguanine nucleotides were likewise prepared.