Synthesis of 13 C-labeled 5-aminoimidazole-4-carboxamide-1-β-D-[13 C5 ] ribofuranosyl 5'-monophosphate.

Abstract

5-Aminoimidazole-4-carboxamide-1-β-D-[13 C5 ] ribofuranosyl 5'-monophosphate ([13 C5 ribose] AICAR-PO3 H2 ) (6) has been synthesized from [13 C5 ]adenosine. Incorporation of the mass-label into [13 C5 ribose] AICAR-PO3 H2 provides a useful standard to aid in metabolite identification and quantification in monitoring metabolic pathways. A synthetic route to the 13 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.