Direct formation and isolation of unprotected α-and β-d-ribopyranosyl urea, α-and β-d-ribofuranosyl urea, and a ribosyl-1,2-cyclic carbamate in carbohydrate melts

Abstract

Solvent-free melts of unprotected d-ribose and urea generated mainly C1- substituted ribosyl products. The remarkable resolving power of a graphitised-carbon HPLC column allowed products of the reaction formed over a range of heating times and temperatures to be monitored. Heating an uncatalysed mixture of d-ribose and urea at temperatures between 75 °C and 90 °C resulted in complex mixtures of compounds; after 19 h heating at 90 °C, up to ten components could be resolved. At shorter heating times and lower temperatures, the composition and distribution of products varied. By manipulation of the reaction time and temperature, and with the addition of an acid catalyst, it was possible to optimise the yields of selected products. Thus, the acid-catalysed reaction after 1–2 h at 80 °C gave optimal yields of α- and β-d-ribopyranosyl urea, whereas the uncatalysed reaction after 22 h at 75–78 °C in addition produced significant amounts of α-d-ribofuranosyl-1,2- cyclic carbamate [glyco-1,2-oxazolidin-2-one] plus the α- and β-ribofuranosyl ureas. The five compounds were isolated and characterised, demonstrating the significant advantages of this approach; its simplicity, and the ability to produce multiple compounds of biological interest in a single step. LC/MS was used to identify tentatively several other components of the reaction mixture. The unprotected title compounds were prepared, isolated and characterised with water as the only solvent.