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

Two novel methods for the preparation of the virtually equimolar mixtures of ( S )- and ( R )-diastereomers of 5-methoxycarbonylhydroxymethyluridine (mchm 5 U) have been developed. The first method involved α-hydroxylation of a 5-malonate ester derivative of uridine (5) with SeO 2 , followed by transformation to ( S )- and ( R )-5-carboxymethyluridines (cm 5 U, 8) and, finally, into the corresponding methyl esters. In the second approach, ( S )- and ( R )-mchm 5 -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 ( S )- and ( R ) diastereomers of mchm 5 U were effectively separated by preparative C18 RP HPLC.