Stereoselective Synthesis of Indazole 2' -Deoxy-b-D-ribonucleosides: Glycosylation of the Nucleobase Anion

The glycosylation of indazolyl anions derived from 4a, b with 2-deoxy-3,5-bis-O-(4-methylbenzoyl)-D-erythro-pentofuranosyl chloride (5) is described. The reaction was Stereoselective - exclusive -D-anomer formation - but regioisomeric N1- and N2-(2-deoxy-D-ribofuranosides) (i.e. 6a and 7a, resp., and 6b and 7b, resp.) were formed in about equal amounts. They were deprotected to yield 8a, b and 9a, b. Compound 1, related to 2-deoxyadenosine (3), and its regioisomer 2 were obtained from 8b and 9b, respectively, by catalytic hydrogenation. The anomeric configuration as well as the position of glycosylation were determined by 1D NOE-difference spectroscopy. The first protonation site of 1 and 2 was found to be the NH2 group. The N-glycosylic bond of 1H-indazole N1-(2-deoxyribofuranosides) is more stable than that of the parent purine nucleosides. Compound 1 is no substrate for adenosine deaminase.