Synthesis of all -trans -Parinaric Acid-d₈ Specifically Deuteriated at All Vinyl Positions

Parinaric acid is a widely used fluorescent probe of biological systems. The all-trans isomer (9(E), 11(E), 13-(E), 15(E)-octadecatetraenoic acid) specifically deuteriated at all vinyl positions wasprepared by using the Wittig reaction to couple a diene phosphorane with an α,β-unsaturated aldehyde-ester. The preparation of each component included the stereoselective reduction ofa substituted propynoic ester with lithium aluminum deuteride (LAD), introducing the trans double bond as well as most of the deuterium in one step, in high isotopic purity without unwanted hydrogen-deuterium exchange. By inclusion of deuterium, the probe can be used with other techniques, such asdeuterium NMR and neutron diffraction, further increasing its utility. The synthesis can be usedto prepare other tetraenes by correct choice of starting propynoic esters.