Facile Solid-Phase Synthesis of AICAR 5'-Monophosphate (ZMP) and Its 4-N-Alkyl Derivatives.

We report herein a facile, solid-phase synthesis of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide-5'-monophosphate (ZMP), a biosynthetic precursor of purine nucleotides,as well as a small collection of its 4-N-alkyl derivatives. Thevery difficult, direct, chemical phosphorylation of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICAR) was cir-cumvented by installing a suitable, fully protected, phos- phate group on the 5'-position of N-1-(2,4-dinitrophenyl)-inosine, connected to the solid support through the 2',3'-posi-tions, prior to the purine degradation, which led to the 5-amino-imidazole-4-carboxamide moiety. A plausible reaction mechanism for the formation of the ZMP imidazole was also reported.