Synthesis of [14,14-2H2]-linolenic acid and its use to confirm the pathway to 12-oxophytodienoic acid (12-oxoPDA) in plants: a conspectus of the epoxycarbonium ion derived family of metabolites from linoleic and linolenic acid hydroperoxides

Abstract

Using acetylene methodology, a synthesis of [14,14-²H₂]-octadeca-9(Z), 12(Z), 15(Z)-trienoic acid is described. The isotopically marked acid is used to distinguish decisively between two possible pathways for the formation of 12-oxophytodienoic acid (12-oxoPDA) by flax enzyme preparation in plants: (a) a route via antarafacial ring closure of a zwitterion derived from an allene epoxide (no loss of 14,14-²H₂) and (b) a pathway resembling the accepted mammalian prostaglandin biosynthesis (loss of one 14-²H). Pathways to metabolic products formed in Nature from linoleic and linolenic acid are summarised in Scheme 3. The entry species is considered to be the epoxy-carbonium ion. Loss of a proton leads to an allene-epoxide from which are formed the α-ketol, the γ-ketol and 12-oxoPDA. A second group of products (colneleic and colnelenic acid, a hemiacetal, its corresponding aldehydes and an epoxy alcohol) are not formed via the allene-epoxide. The epoxy-carbonium ion can be trapped as an epoxy alcohol or rearranged via a vinyl-oxonium ion with capture by water to form a hemiacetal. Alternatively, loss of a proton from the epoxy-carbonium ion or vinyl-oxonium ion leads to colneleic and colnelenic acid.