A New and Efficient Synthesis of Guanosine

Article abstract of DOI:10.1021/jo00358a021

New methodology for the preparation of guanosine-type nucleoside analogues from o-amino carbamyl nucleoside precursors has been developed and is demonstrated by the three-step, high-yield synthesis of guanosine (16) from 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (1, AICA-riboside).Treatment of 1-(alkoxycarbonyl)-3-(arylmethyl)thioureas 8 with phosgene in the presence of triethylamine affords the highly electrophilic 1-(alkoxycarbonyl)-3-(arylmethyl)carbodiimide reagents 9 in high yield.These reagents are shown to condense with AICA-riboside readily at room temperature to afford N-acyl-N'-(arylmethyl)guanidino-substituted imidazole nucleoside derivatives.One of these derivatives, 5-(N-benzyl-N'-(ethoxycarbonyl)guanidino)-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (11a), is smoothly debenzylated with cyclohexene in the presence of Pd(0) to afford 5-(N-(ethoxycarbonyl)guanidino)-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (14).Prolonged heating of 14 in ethanol at reflux affords N-2-(ethoxycarbonyl)guanosine (15) in high yield.The ethoxycarbonyl protecting group of 15 is removed with concentrated NH4OH/pyridine to afford guanosine.This new methodology is much more efficient than those previously reported and should find application for the preparation of a wide variety of guanosine-type nucleoside analogues.