Synthesis of site-specifically deuterated arachidonic acid derivatives containing a remote tritium radiolabel

Abstract

The synthesis of arachidonic acid derivatives containing site-specifically incorporated deuterium atoms and also a remote tritium label are described. Deuterium incorporation at the C11 and/or C15 position was achieved using Wittig chemistry, while the radiolabel was introduced at a remote position using [(3)H]NaBH(4) as the radiolabel source. These compounds can be used to measure secondary kinetic isotope effects for both cyclooxygenase and lipoxygenase enzymes under aerobic turnover with high precision.