Synthesis, NMR analysis and applications of isotope-labelled hydantoins

Abstract

This review concerns methods of synthesis, NMR analysis and applications of isotope-labelled hydantoins. The hydantoin moiety is present in natural products and in extraterrestrial ice, indicating this to be an important compound in prebiotic chemistry. Bacterial transport proteins that scavenge hydantoins have been identified, isolated and characterised with isotope-labelling of hydantoins as an essential requirement to achieve this. These are Mhp1 from Microbacterium liquefaciens and PucI from Bacillus subtilis, transporting 5-aryl-substituted hydantoins and allantoin, respectively. The hydantoin ring is a useful centre in synthetic chemistry, especially for combinatorial chemistry, multicomponent reactions and in diversity-oriented synthesis. It is also found in pharmacologically active molecules, such as the anticonvulsant phenytoin. Hydantoins synthesised with isotope labels include hydantoin itself, allantoin, other 5-monosubstituted derivatives, phenytoin, other 5,5-di-substituted derivatives, N-substituted derivatives and other more complex molecules with multiple substituents. Analysis of isotope-containing hydantoins by NMR spectroscopy has been important for confirming purity, labelling integrity, specific activity and molecule conformation. Isotope-labelled hydantoins have been used in a range of biological, biomedical, food and environmental applications including metabolic and in vivo tissue distribution studies, biochemical analysis of transport proteins, identification and tissue distribution of drug binding sites, drug metabolism and pharmacokinetic studies and as an imaging agent.