Synthesis of deuterium labeled ezetimibe and its glucuronide conjugate

Ezetimibe is an effective cholesterol absorption inhibitor approved for the combined treatment with statins to reduce LDL-C level. Ezetimibe labeled with deuterium was applied for drug metabolism studies. [2H5] fluorobenzene was applied to preprare [2H4] ezetimibe. Stable isotope labeled ezetimibe was obtained in seven steps with a 29.3% overall yield. Stable isotope labeled glucuronide-ezetimibe, the most abundant metabolite of ezetimibe was also synthesized.