Intramolecular thermal reactions of the derivatives of 5′-azido-5′-deoxyuridine. A new feasible route to the regio- and stereospecific synthesis of reversed nucleosides carrying a substituted five-membered heterocycle

Summary

With a view to probing the reactivity of the “naked” 5,6-double bond of uracil nucleosides as a dipolarophile, l-(5′-azido-5′-deoxy-2′,3′- O -isopropylidene-ß-D-ribofuranosyl)uracil ( l a) and its analogs l b-d were synthesized and submitted to an intramolecular thermal reaction, which yielded N ^l ,5′-anhydro-Nω-(2′,3′- O -isopropylidene-β-D-ribofuranosyl)-4-allophanoyl-1,2,3-triazole ( 3 a) and its analogs 3 b-c in moderate to high yields with 6,5′-imino cyclouridine derivatives ( 4 ) as minor products. The intermediary cycloadduct 2 was trapped as 9,5′-cyclo-3-(2′,3′-O-isopropylidene-β-D-ribofuranosyl)-8-azaxanthine (5). Compounds 3 c and 3 a were regio- and stereospecifically transformed to 4-methoxy and carboxamido substituted triazole reversed nucleosides 7 a-b and ll a-b.