Formation of N-carbamoylaspartic acid and its cyclisation to orotic acid

Abstract

The stereochemistries of the reactions between cyanate and aspartic acid and 3-methylaspartic acid have been examined. The product of the first reaction, N-carbamoylaspartic acid 3. can cyclise to give either dihydroorotic acid 5 or 5-carboxymethylhydantoin 4. Acid catalysed cyclisation gives the latter while catalysis by the enzyme dihydroorotase gives the former. Introduction of a double bond into 3 changes the course of non-enzymatic cyclisation and a six-membered ring compound orotic acid 1 is the product. It is proposed that the double bond prevents intramolecular hydrogen bonding.