Heterocyclic Synthesis via a 1,3-Dicyclohexylcarbodiimide-Mediated Cyclodesulfurative Annulation Reaction. New Methodology for the Preparation of Guanosine and Guanosine-Type Nucleoside Analogues

Article abstract of DOI:10.1021/jo00357a022

Treatment of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (1, AICA-ribonucleoside) with methoxycarbonyl isothiocyanate followed by cyclodesulfurization of the resulting methoxycarbonylated thioureido derivative with 1,3-dicyclohexylcarbodiimide (DCC) has furnished 5-<3-(methoxycarbonyl)-1-ureido>-1-β-D-ribofuranosylimidazole-4-carbonitrile (6), not 2-<(methoxycarbonyl)amino>-9-β-D-ribofuranosylpurin-6-one (4).Using 1 labeled with 18O in the carboxamide moiety, the conversion of 1 to 6 is shown to proceed with retention of the 18O label.This finding has suggested the presence of a <1,3>oxazine intermediate in an intramolecular dehydration reaction mechanism.Under similar reaction conditions, methyl 5-amino-1-β-D-ribofuranosylimidazole-4-carboximidate (13) affords 6-methoxy-2-<(methoxycarbonyl)amino>-9-β-D-ribofuranosylpurine (14), which gives guanosine upon deprotection with iodotrimethylsilane.The use of this methoxycarbonyl isothiocyanate/DCC cyclodesulfurization method on heterocyclic o-amino carboximidate esters thus provides a highly efficient entry into the class of guanosine-type nucleoside analogues.