Fluorooleic acid

This reagent does not react with double bonds, as demonstrated when fluorooleic acids were prepared from the corresponding hydroxyoleic acids and incorporated by enzymes into living cells163. Acetylenes do not react with DAST either, but ynones do and produce difluoroacetylenes164. The reaction was used by Kobayashi and coworkers to prepare difluoroleukotriene 16 with similar biological effects to arachidonic acid (equation 91)165. 

The discovery in 1943 by Marais (12) that potassium fluoro-acetate was the toxic material present in a mmiber of South African plants attracted notable attention, though the reasons for the toxicity were not then known. Further exploration showed the presence of the similarly toxic u-fluorooleic acid in other plants. 

In the cellular metabolism F. reacts with citrate synthase to form (2R,3R)-2-fluorocitrate (QH7FO7, Mr 210.12), which inhibits transport of citrate through mitochondrial membranes. The lethal synthesis of fluorocitrate, however, only contributes to a small extent to the toxic activity. D. toxicarium stores F. in its extremely toxic seeds in the form of cu-fluorofatty acids, principally co-fluorooleic acid (C,gH33F02, Mr 300.46). Fluoroacetyl-CoA functions here as a starter unit. The biosynthesis of F. from fluoride ions has not been elucidated. 

Consider the following sequence of reactions, taken from the early steps in a synthesis of -fluorooleic acid, a toxic natural compound from an African shrub. ( -Fluorooleic acid, also called ratsbane, has been used to kill rats and also as an arrow poison in tribal warfare. Two more steps beyond those below are required to complete its synthesis.)... 

Answer Oxidation of co-fluorooleate in the /3-oxidation pathway forms fluoroacetyl-CoA in the last pass through the sequence. Entry of fluoroacetyl-CoA into the citric acid cycle produces fluorocitrate, a powerful inhibitor of the enzyme aconitase. As a result of this inhibition, the citric acid cycle shuts down and the flow of reducing equivalents to oxidative phosphorylation is fatally impaired. 

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