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. (Figure presented.).