8-AZA-2'-DEOXYGUANOSINE AND RELATED 1,2,3-TRIAZOLO[4,5-D]PYRIMIDINE 2'-DEOXYRIBOFURANOSIDES

Abstract

The synthesis of 8-azaguanine N-9-, N8-, and N7-(2'-deoxyribonucleosides) 1-3, related to 2'-deoxyguanosine (4), is described. Glycosylation of the anion of 5-amino-7-methoxy-3H-1,2,3-triazolo[4,5-d]pyrimidine (5) with 2-deoxy-3,5-di-O-(4-toluoyl)-alpha-D-erythro-pentofuranosyl chloride (6) afforded the regioisomeric glycosylation products 7a/7b, 8a/8b, and 9 (Scheme 1) which were detoluoylated to give 10a, 10b, 11a, 11b, and 12a. The anomeric configuration as well as the position of glycosylation were determined by combination of UV, C-13-NMR, and H-1-NMR NOE-difference spectroscopy. The 2-amino-8-aza-2'-deoxyadenosine (13), obtained from 7a, was deaminated by adenosine deaminase to yield 8-aza-2'-deoxyguanosine (1), whereas the N7- and N8-regioisomers were no substrates of the enzyme. The N-glycosylic bond of compound 1 (0.1 N HCl) is ca. 10 times more stable than that of 2'-deoxyguanosine (4).