Synthesis of new nucleosides by coupling of chloropurines with 2- and 3-deoxy derivatives of N-methyl-D-ribofuranuronamide

The synthesis of new deoxyribose nucleosides by coupling chloropurines with modified D-ribose derivatives is reported. The methyl 2-deoxy-N-methyl-3-O-(p-toluoyl)-alpha-D-ribofuranosiduronamide (alpha-D-8) and the corresponding anomer beta-D-8 were synthesized starling from the commercially available 2-deoxy-D-ribose (1) (Scheme 1). Reaction of alpha-D-8 with the silylated derivative of 2,6-dichloro-9H-purine (9) afforded regioselectively the N-9-(2'-deoxyribonucleoside) 10 as anomeric mixture (Scheme 2), whereas beta-D-8 did not react. Glycosylation of 9 or of 6-chloro-9H-purine (17) with 1,2-di-O-acetyl-3-deoxy-N-methyl-beta-D-ribofuranuronamide (13) yielded only the protected beta-D-anomers 14 and 18, respectively (Scheme 3). Subsequent deacetylation and dechlorination afforded the desired nucleosides beta-D-11, beta-D-12, 15, and 16. The 3'-deoxy-2-chloroadenosine derivative 15 showed the highest affinity and selectivity for adenotin binding site vs. A(1) and A(2A) adenosine receptor subtypes.