Synthesis of Linoleoyl ethanolamide

Abstract

Linoleoyl ethanolamide has been showed to serve as a new and additional class of endogenous signaling molecule and exhibited a variety of biological activities in cells and tissues. Herein, we reported an effective method for the synthesis of linoleoyl ethanolamide. Enzymatic and chemical syntheses of linoleoyl ethanolamide were first compared and then reaction conditions were optimized. When the reaction was conducted at 30°C for 1 h by reacting 0.5 mmol methyl linoleate with 5 mmol ethanolamine in the presence of 15 μL, 5.4 mol/L sodium methoxide in methanol as catalyst, 97.2% linoleoyl ethanolamide was produced in the crude reaction mixture without further purification after the removal of excess ethanolamine. Additionally, the reaction can be conducted on a large scale, which resulted in the formation of 95.9% linoleoyl ethanolamide. Compared to previous studies, the amidation reaction between methyl linoleate and ethanolamine with sodium methoxide as catalyst for the synthesis of linoleoyl ethanolamide is more effective and faster. In addition, the reaction is scalable and reaction conditions are mild. This is the first time to use methyl linoleate to synthesize linoleoyl ethanolamide. Commercial linoleoyl ethanolamide is very expensive. However, the scalability and ease for such synthesis make it possible to study the biological and nutritional functions of the cannabinoid-like linoleoyl ethanolamide in animal or human subjects. ©2013 by Japan Oil Chemists' Society.