Synthesis of site-specifically 13C labeled linoleic acids

Abstract

Soybean lipoxygenase-1 (SLO-1) catalyzes the C–H abstraction from the reactive carbon (C-11) in linoleic acid as the first and rate-determining step in the formation of alkylhydroperoxides. While previous labeling strategies have focused on deuterium labeling to ascertain the primary and secondary kinetic isotope effects for this reaction, there is an emerging interest and need for selectively enriched 13C isotopologues. In this Letter, we present synthetic strategies for site-specific 13C labeled linoleic acid substrates. We take advantage of a Corey–Fuchs formyl to terminal 13C-labeled alkyne conversion, using 13CBr4 as the labeling source, to reduce the number of steps from a previous fatty acid 13C synthetic labeling approach. The labeled linoleic acid substrates are useful as nuclear tunneling markers and for extracting active site geometries of the enzyme–substrate complex in lipoxygenase.