SYNTHESIS OF NEW NUCLEOSIDES BY COUPLING OF CHLOROPURINES WITH 2-DEOXY 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 hyl-3-O-(p -toluoyl)-alpha-D-ribofuranosiduronamide (alpha-D-8) and the correspon ding anomer beta-D-8 were synthesized starling from the commercially a vailable 2-deoxy-D-ribose (1) (Scheme 1). Reaction of alpha-D-8 with t he silylated derivative of 2,6-dichloro-9H-purine (9) afforded regiose lectively the N-9-(2'-deoxyribonucleoside) 10 as anomeric mixture (Sch eme 2), whereas beta-D-8 did not react. Glycosylation of 9 or of 6-chl oro-9H-purine (17) with -acetyl-3-deoxy-N-methyl-beta-D-ribofuranurona mide (13) yielded only the protected beta-D-anomers 14 and 18, respect ively (Scheme 3). Subsequent deacetylation and dechlorination afforded the desired nucleosides beta-D-11, beta-D-12, 15, and 16. The 3'-deox y-2-chloroadenosine derivative 15 showed the highest affinity and sele ctivity for adenotin binding site vs. A(1) and A(2A) adenosine recepto r subtypes.