Synthesis of New Nucleosides by coupling of chloropurines with 2‐ and 3‐deoxy derivatives of N‐methyl‐D‐ribofuranuronamide

Abstract

AbstractThe 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)‐α‐D‐ribofuranosiduronamide (α‐D‐8) and the corresponding anomer β‐D‐8 were synthesized starting from the commercially available 2‐deoxy‐D‐ribose (1) (Scheme 1). Reaction of α‐D‐8 with the silylated derivative of 2,6‐dichloro‐9H‐purine (9) afforded regioselectively the N9‐(2′‐deoxyribonucleoside) 10 as anomeric mixture (Scheme 2), whereas β‐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‐β‐D‐ribofuranuronamide (13) yielded only the protected β‐D‐anomers 14 and 18, respectively (Scheme 3). Subsequent deacetylation and dechlorination afforded the desired nucleosides β‐D‐11, β‐D‐12,15, and 16. The 3′‐deoxy‐2‐chloroadenosine derivative 15 showed the highest affinity and selectivity for adenotin binding site vs. A1 and A2A adenosine receptor subtypes.