Photooxidation of 18-Carbon Polyunsaturated Fatty Acids to Prepare Mono-Hydroxylated Octadecanoids.

Oxylipins are oxygenated products of fatty acids that are being increasingly studied due to their role in multiple physiological processes. Investigations to date have focused on the 20-carbon eicosanoids and 22-carbon docosanoids. However, more recently, interest has grown into the 18-carbon octadecanoids. A significant obstacle in the study of these compounds is a lack of authentic standards for functional studies as well as for development of methods for their quantification. We developed a fast and simple one-step synthetic strategy to produce mono-hydroxylated metabolites based on the photosensitized oxidation of 18-carbon polyunsaturated fatty acids (PUFAs). Four different PUFAs including α-linolenic acid (ALA, ω3), γ-linolenic acid (GLA, ω6), stearidonic acid (SDA, ω3), and octadecapentaenoic acid (ODPA, ω3) were photooxidized in the presence of methylene blue and oxygen under exposure to light from a halogen lamp. The uncommon PUFA ODPA was prepared from docosahexaenoic acid (DHA, ω3) in a 6-step synthesis with 30% overall yield. The hydroperoxide products were reduced with sodium borohydride and the mono-hydroxylated octadecanoids were separated by HPLC. Product identification was performed by GC-MS. The final purities of isolated products ranged from 80% to 98%, with oxidation of non-terminal double bonds being preferred. It is likely that this approach could be extended to PUFAs of varying chain length, suggesting that photosensitized oxidation could be employed to rapidly prepare hydroperoxides from multiple unsaturated fatty acids. As interest in oxylipins continues to increase, this approach will be useful for large-scale preparation of multiple standards for the study of these new compounds.