8-AZAADENINE 2',3'-DIDEOXYRIBONUCLEOSIDES - SYNTHESIS VIA 1,2,3-TRIAZOLO[4,5-D]PYRIMIDINYL ANIONS

Abstract

The 8-azaadenine 2',3'-dideoxyribonucleosides 1-3 were synthesized via glycosylation of the 7-methoxy- or 7-amino-3H-1,2,3-triazolo[4,5-d]pyrimidinyl anion with 5-O-[(tert-butyl)dimethylsilyl]-2,3-dideoxy-D-glycero-pentofuranosyl choride (6). As 6 was an anomeric mixture, anomeric glycosylation products were formed. Moreover, three regioisomers (N1, N2, and N3) were obtained in the case of the methoxy compound, but only two (N1 and N2) using 8-azaadenine. They were characterized by C-13-NMR and CD spectra. The N-glycosylic bond of 8-aza-2',3'-dideoxyadenosine (1) was ca. 10 times more stable against acid than that of 2',3'-dideoxyadenosine. Compound 1 was deaminated by adenosine deaminase and showed inhibitory activity on HIV reverse transcriptase in form of its O-5'-triphosphate.