SYNTHESIS OF SUGAR-MODIFIED 2,6-DIAMINOPURINE AND GUANINE NUCLEOSIDESFROM GUANOSINE VIA TRANSFORMATIONS OF 2-AMINOADENOSINE AND ENZYMATIC DEAMINATION WITH ADENOSINE-DEAMINASE

Treatment of 2,6-diaminopurine riboside (2-aminoadenosine) with alpha- acetoxyisobutyryl bromide in acetonitrile gave mixtures of the trans 2 ',3'-bromohydrin acetates 2. Treatment of 2 with zinc-copper couple ef fected reductive elimination, and deprotection gave -dideoxy-beta-D-er ythro-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'-deox y 6a and 3'-deoxy 7a nucleosides. Treatment of the 3',5'-O-(tetraisopr opyldisiloxanyl) derivative (5a) with trifluoromethanesulfonyl chlorid e-4-(dimethylamino)pyridine gave 2'-triflate 5c. Displacement with lit hium azide dimethylformamide and deprotection gave the arabino 2'-azid o derivative 8a, which was reduced to give -9-(2-amino-2-deoxy-beta-D- arabinofuranosyl)purine (8b). Sugar-modified 2,6-diaminopurine nucleos ides were treated with adenosine deaminase to give the corresponding g uanine analogues.