Synthesis of Microbial‐Derived Octadecanoids

ABSTRACT Gut bacteria can convert dietary fatty acids into oxygenated metabolites called oxylipins, which can exert potent lipid mediator functions. The oxylipins derived from C‐18 fatty acids are termed octadecanoids and associate with multiple disorders including allergy and metabolic dysregulation. This study presents the synthesis of 17 octadecanoids possessing a hydroxy group ( n = 9) or a ketone ( n = 8) on the 10‐ or 13‐positions. The products of these two series were prepared for the linoleic acid (LA), α‐linolenic acid (ALA) and γ‐linolenic acid (GLA) pathways. The synthetic strategies provided 17 putative microbial metabolites of C‐18 polyunsaturated fatty acids (PUFAs) with high purities, in 5–13 steps and overall yields from 1.5%–37%. To study the biological formation of these compounds, the parent PUFAs (LA, ALA, GLA) were fed to cultures of Enterococcus faecalis U150 and Lactobacillus acidophilus CCUG 5917, and the octadecanoid products were measured by chiral supercritical fluid chromatography coupled to tandem mass spectrometry (SFC‐MS/MS). The compounds containing a hydroxy group on the 10‐ or 13‐position are racemic, forming 9 enantiomeric pairs. Accordingly, of the 17 compounds synthesized, 9 were chiral and 8 were achiral resulting in 26 compounds. An additional 7 commercial bacteria‐derived octadecanoids were measured to provide a screen of 33 compounds. Generally, PUFA supplementation resulted in selective formation of the associated octadecanoids. Of the 33 studied compounds, 16 were observed to be formed by E. faecalis and 13 by L. acidophilus . These findings demonstrate the bacteria species‐specific formation of octadecanoids, which may have ramifications for associated biological response in the host.