Scalable Synthesis of 2,2′-Anhydro-arabinofuranosyl Imidazoles

Abstract

We report the efficient and scalable synthesis of 2,2′-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide and 2,2′-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carbonitrile from commercial arabino-adenosine. 2,2′-Anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide is synthesised in only five steps with a single chromatographic purification. Additionally, we report a high-yielding, three-step conversion of 2,2′-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide into 2,2′-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carbonitrile. They are proposed key intermediates of the divergent prebiotic synthesis of ribonucleotides and this facile synthesis is anticipated to be instrumental in continued investigation of the origins of nucleotides.