8-AZAGUANINE 2',3'-DIDEOXYRIBONUCLEOSIDES - GLYCOSYLATION OF THE MINO-7-METHOXY-3H-1,2,3-TRIAZOLO[4,5-D]PYRIMIDINYL ANION WITH 2,3-DIDEOXY-D-GLYCERO-PENTOFURANOSYL CHLORIDE

The synthesis of the regioisomeric 8-azaguanine N7-, N8-, and N-9-(bet a-D-2',3'-dideoxyribonucleosides) (1, 2, and 3, respectively) and of t he diamino derivative 13 is described. The anion of mino-7-methoxy-3H- 1,2,3-tri-azolo[4,5-d]pyrimidine (5) was glycosylated with imethylsily l]-2,3-dideoxy-D-glycero-pentofuranosyl chloride (6; anomeric mixture) , yielding the regioisomeric 2',3'-dideoxyribofuranosides as anomeric mixtures 7a/10a, 8a/11a, and 9a/12a. They were desilylated with Bu4NF in THF affording the 5-amino-7-methoxy-nucleosides 7b-12b. Treatment w ith aqueous NaOH gave the beta-azaguanine beta-D-2',3'-dideoxynucleosi des 1-3 and their alpha-D-anomers 14-16. The reaction of 7b with NH3/M eOH yielded the diamino compound 13. The N-glycosylic bond of 8-aza-2' ,3'-dideoxyguanosine (1) is four-times more stable against acid than t hat of 2',3'-dideoxyguanosine. Compounds 1, 2, and 13 were converted t o their 5'-triphosphates 17-19 which showed only modest inhibitory act ivity against HIV-reverse transcriptase.