Novel entry to the synthesis of ()- and ()-5-methoxycarbonylhydroxymethyluridines - a diastereomeric pair of wobble tRNA nucleosides.

Two novel methods for the preparation of the virtually equimolar mixtures of ()- and ()-diastereomers of 5-methoxycarbonylhydroxymethyluridine (mchmU) have been developed. The first method involved α-hydroxylation of a 5-malonate ester derivative of uridine (5) with SeO, followed by transformation to ()- and ()-5-carboxymethyluridines (cmU, 8) and, finally, into the corresponding methyl esters. In the second approach, ()- and ()-mchm-uridines were obtained starting from 5-formyluridine derivative (9) by hydrolysis of the imidate salt (11) prepared in the acid catalyzed reaction of 5-cyanohydrin-containing uridine (10b) with methyl alcohol. In both methods, the ()- and () diastereomers of mchmU were effectively separated by preparative C18 RP HPLC.