Synthesis of sugar-modified 2,6-diaminopurine and guanine nucleosides from guanosine via transformations of 2-aminoadenosine and enzymatic deamination with adenosine deaminase

Article abstract of DOI:10.1139/v97-092

Treatment of 2,6-diaminopurine riboside (2-aminoadenosine) with α- acetoxyisobutyryl bromide in acetonitrile gave mixtures of the trans 2',3'- bromohydrin acetates 2. Treatment of 2 with zinc-copper couple effected reductive elimination, and deprotection gave 2,6-diamino-9-(2,3-dideoxy-β- D-erythro-pent-2-enofuranosyl)purine (3a). Treatment of 2 with Dowex 1 x 2 (OH^-) resin in methanol gave the 2',3-anhydro derivative 4. Stannyl radical- mediated hydrogenolysis of 2 and deprotection gave the 2'-deoxy 6a and 3'- deoxy 7a nucleosides. Treatment of the 3',5'-O-(tetraisopropyldisiloxanyl) derivative (5a) with trifluoromethanesulfonyl chloride - 4- (dimethylamino)pyridine gave 2'-triflate 5c. Displacement with lithium azide -dimethylformamide and deprotection gave the arabino 2'-azido derivative 8a, which was reduced to give 2,6-diamino-9 (2-amino-2-deoxy-β-D- arabinofuranosyl)purine (8b). Sugar-modified 2,6-diaminopurine nucleosides were treated with adenosine deaminase to give the corresponding guanine analogues. Treatment of 2,6-diaminopurine riboside (2-aminoadenosine) with α-acetoxyisobutyryl bromide in acetonitrile gave mixtures of the trans 2',3'-bromohydrin acetates 2. Treatment of 2 with zinc-copper couple effected reductive elimination, and deprotection gave 2,6-diamino-9-(2,3-dideoxy-β-D-erythro-pent-2-enofuranosyl) purine (3a). Treatment of 2 with Dowex 1 × 2 (OH^-) resin in methanol gave the 2',3'-anhydro derivative 4. Stannyl radical-mediated hydrogenolysis of 2 and deprotection gave the 2'-deoxy 6a and 3'-deoxy 7a nucleosides. Treatment of the 3',5'-O-(tetraisopropyldisiloxanyl) derivative (5a) with trifluoromethanesulfonyl chloride - 4-(dimethylamino)pyridine gave 2'-triflate 5c. Displacement with lithium azide - dimethylformamide and deprotection gave the arabino 2'-azido derivative 8a, which was reduced to give 2,6-diamino-9-(2-amino-2-deoxy-β-D-arabinofuranosyl)purine (8b). Sugar-modified 2,6-diaminopurine nucleosides were treated with adenosine deaminase to give the corresponding guanine analogues.