Synthesis of highly pure ¹⁴C-labelled DL-allantoin and ¹³C NMR analysis of labelling integrity

Graphical Abstract

A number of synthetic approaches are assessed to prepare DL-allantoin labelled with ¹⁴C given certain requirements and technical limitations. A method that fulfils these criteria is described to achieve the synthesis of highly pure ¹⁴C-labelled DL-allantoin with the label introduced to the ureido carbonyl group in the final step by [¹⁴C]urea. NMR analysis of ¹³C-labelled DL-allantoin produced by the same method confirms partial scrambling of the label to C-2. Copyright © 2009 John Wiley & Sons, Ltd.

Abstract

A number of synthetic approaches are assessed to prepare allantoin labelled with ¹⁴C given certain requirements and technical limitations. A method that fulfils these criteria is described to achieve the synthesis of highly pure ¹⁴C-labelled allantoin with the label introduced to the ureido carbonyl group in the final step by reaction of 5-chlorohydantoin with [¹⁴C]urea. The chosen method favours high purity at the expense of radiochemical yield, which is achieved at a level of 8%. The integrity of the label is then investigated by performing an NMR analysis of ¹³C-labelled allantoin synthesized by the same method. The ¹³C NMR spectrum confirms partial scrambling of the label to the C-2 position by equilibration of the product via a putative bicyclic intermediate, which had been suggested by other workers. The ¹⁴C-labelled allantoin synthesized by this method is therefore assigned as DL-[H₂N¹⁴CO/¹⁴C-2]allantoin. This study also includes the first full characterization of a side product, 5-hydroxy-5-methoxyhydantoin, obtained by the reaction of a 5-hydroxyhydantoin intermediate with the methanol solvent. Copyright © 2009 John Wiley & Sons, Ltd.