Model studies on the decarboxylation of orotic acid analogues

Orotidine 5’-monophosphate, also known as orotidylic acid, is a precursor to the pyrimidine nucleotides. Orotidine 5’-monophosphate decarboxylase (OMP decarboxylase, ODCase) catalyzes the decarboxylation of OMP to uridine monophosphate.  The mechanism of the reaction, however, remains unknown. We are investigating the mechanism of ODCase using the decarboxylation of the orotic acid analogues as a model system.  In this study, we investigate how hydrogen bonds to the pyrimidine functional group affect the rate of decarboxylation.  We will study the reaction in the presence of hydrogen bonding partners in various solvents.  In less polar and aprotic solvents, the effect of hydrogen bonding should be greater.  In order to carry out the study, orotic acid analygues more soluble in less polar solvent need to be prepared.  The synthesis and characterization of 1-cyclohexylorotic acid is discussed.