Synthesis of perdeuterated linoleic acid-d31 and chain deuterated 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine-d62

Herein, we report a gram-scale synthesis of perdeuterated linoleic acid-d31. The starting materials for the synthesis are two saturated fatty acids, azelaic acid-d14 and pentanoic acid-d9, which can be obtained by metal catalysed hydrothermal hydrogen-deuterium exchange. The synthesis utilises the fatty acids directly via decarboxylative coupling. Copper catalysed coupling of a terminal alkyne intermediate with a propargyl bromide derivative affords a skipped diyne, which can be reduced using P-2 nickel to obtain the desired cis,cis-diene geometry. The subsequent synthesis of the tail-deuterated phospholipid, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine-d62 (PLPC-d62) is also described. Optimised reaction conditions were developed to access this phospholipid and its regioisomeric purity was characterised by two complementary mass spectrometry techniques. © 2022 The Authors - CC- BY Licence
Deuteration, Linoleic acid, Synthesis, Phospholipids, Mass spectroscopy, Cell membranes, Enzymes, Lipids, Deuterium, Labelling
Moir, M., Yepuri, N. R., Marshall, D. L., Blanksby, S. J., & Darwish, T. A. (2022). Synthesis of perdeuterated linoleic acid-d31 and chain deuterated 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine-d62. Advanced Synthesis & Catalysis, 364(21), 3670-3681. doi:10.1002/adsc.202200616