Synthesis of C-labeled 5-aminoimidazole-4-carboxamide-1-β-D-[ C ] ribofuranosyl 5'-monophosphate.

5-Aminoimidazole-4-carboxamide-1-β-D-[ C ] ribofuranosyl 5'-monophosphate ([ C ribose] AICAR-PO H ) (6) has been synthesized from [ C ]adenosine. Incorporation of the mass-label into [ C ribose] AICAR-PO H provides a useful standard to aid in metabolite identification and quantification in monitoring metabolic pathways. A synthetic route to the C-labeled compound has not been previously reported. Our method employs a hybrid enzymatic, and chemical synthesis approach that applies an enzymatic conversion from adenosine to inosine followed by a ring-cleavage of the protected inosine. A direct phosphorylation of the resulting 2',3'-isopropylidine acadesine (5) was developed to yield the title compound in 99% purity following ion exchange chromatography.