Manufacture of (5Z,8Z,11Z,13E)(15S)-15-Hydroxyeicosa-5,8,11,13-tetraenoic Acid Sodium Salt for Clinical Trials

A robust synthesis of (5Z,8Z,11Z,13E)(15S)-15-hydroxyeicosa-5,8,11,13-tetraenoic acid (15(S)-HETE) sodium salt was established, utilising a biooxidation process. Treatment of arachidonic acid with soybean lipoxidase in 0.1 M sodium tetraborate buffer under oxygen pressure resulted in formation of the hydroperoxide, 15(S)-HPETE. Addition of sodium borohydride to the reaction mixture reduced the hydroperoxide to 15(S)-HETE, which was then purified by column chromatography. 15(S)-HETE sodium salt was prepared by treatment of an ethanol solution of HETE with aqueous sodium hydrogen carbonate. Multiple 10-g batches of 15(S)-HETE sodium salt with >98% enantiomeric excess and >98% chemical purity were prepared to support clinical trials.