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)‐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‐9 H ‐purine ( 9 ) afforded regioselectively the N 9 ‐(2′‐deoxyribonucleoside) 10 as anomeric mixture ( Scheme 2 ), whereas β‐ D ‐ 8 did not react. Glycosylation of 9 or of 6‐chloro‐9 H ‐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. A 1 and A 2A adenosine receptor subtypes.