Synthesis of 4- N-alkyl and ribose-modified AICAR analogues on solid support

Herein, we report the solid-phase synthesis of several 5-aminoimidazole-4-(N-alkyl)carboxamide-1-ribosides (4-N-alkyl AICARs) and the corresponding 2?,3?-secoriboside derivatives. The method uses the N-1-dinitrophenyl-inosine 5?-bonded to a solid support. This inosine derivative has the C-2 of the purine base strongly activated towards the attack of N-nucleophiles thus allowing the preparation of several N-1 alkylated inosine supports from which a small library of 4-N-alkyl AICAR derivatives has been synthesized. A set of new 4-N-alkyl AICA-2?,3?-secoriboside derivatives have also been obtained in high yields by solid-phase cleavage of the 2?,3?-ribose bond.