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.