Facile and Stereoselective Synthesis of (Z)-15-Octadecenoic Acid and (Z)-16-Nonadecenoic Acid: Monounsaturated Omega-3 Fatty Acids

Facile syntheses of the monounsaturated omega-3 fatty acids, (Z)-15-octadecenoic acid and (Z)-16-nonadecenoic acid, are presented. Commercially available hydroxy fatty acids were esterified and oxidised, followed by the Wittig reaction to introduce the omega-3 olefinic bond; hydrolysis yielded the omega-3 fatty acids in high purity. An examination of different reaction conditions for the Wittig step found that THF as solvent and coupling temperatures of ?78 °C gave optimal stereoselectivity, affording the omega-3 olefins in Z:E ratios ≥97:3. The syntheses have overall yields of ~43%, and utilise straightforward, robust chemistry, that may be readily scaled up and reproduced. Also presented is a method for accurately determining the double bond geometry and isomeric purity of the fatty acid products using ¹H–¹³C-HSQC NMR and GC–MS, respectively.