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

Abstract

The synthesis of the regioisomeric 8-azaguanine N7-, N8-, and N-9-(beta-D-2',3'-dideoxyribonucleosides) (1, 2, and 3, respectively) and of the diamino derivative 13 is described. The anion of 5-amino-7-methoxy-3H-1,2,3-tri-azolo[4,5-d]pyrimidine (5) was glycosylated with 5-O-[(tert-butyl)dimethylsilyl]-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 with aqueous NaOH gave the beta-azaguanine beta-D-2',3'-dideoxynucleosides 1-3 and their alpha-D-anomers 14-16. The reaction of 7b with NH3/MeOH yielded the diamino compound 13. The N-glycosylic bond of 8-aza-2',3'-dideoxyguanosine (1) is four-times more stable against acid than that of 2',3'-dideoxyguanosine. Compounds 1, 2, and 13 were converted to their 5'-triphosphates 17-19 which showed only modest inhibitory activity against HIV-reverse transcriptase.