Synthesis of new 3 '-deoxyribonucleosides employing the acid-catalyzed fusion method

Coupling of 4,6-dichloro-1H-imidazo[4,5-c]pyridine (2.6-dichloro-3-deaza-9H -purine) (I) with 1,2-O-diacetyl-5-O-benzoyl-3-deoxy-beta-D-ribofuranose (2 ), employing the acid-catalyzed fusion method, is reported (Scheme I). The condensation reaction was regioselective and gave the three N-1-glycosylati on products 3-5, whereas no N-3-nucleosides were detected. Treatment of 3-5 with methanolic ammonia afforded the corresponding deprotected nucleosides 6-8. Compounds 6 and 7 were assigned the structure of the beta-D- and alph a-D-anomeric N-1-(3'-deoxyribo)nucleosides, respectively. The third derivat ive 8 proved to be the alpha-D-anomer of a 3'-deoxyarabinonucleoside derivi ng from epimerization at C(2) of the sugar. The 2-chloro- and N-6-substitut ed derivatives 9, 11, and 13 of 3'-decxy-3-deazaadenosine (10) and of its a lpha-D-anomer 12 can be obtained from these versatile synthons (Schemes 2 a nd 3).