Synthesis and Liver Microsomal Metabolic Stability Studies of a Fluorine‐Substituted δ‐Tocotrienol Derivative

Abstract A fluoro‐substituted δ‐tocotrienol derivative, DT3‐F2, was synthesized. This compound was designed to stabilize the metabolically labile terminal methyl groups of δ‐tocotrienol by replacing one C−H bond on each of the two methyl groups with a C−F bond. However, in vitro metabolic stability studies using mouse liver microsomes revealed an unexpected rapid enzymatic C−F bond hydrolysis of DT3‐F2. To the best of our knowledge, this is the first report of an unusual metabolic hydrolysis of allylic C−F bonds.