Synthesis of Perdeuterated Linoleic Acid‐d₃₁ and Chain Deuterated 1‐Palmitoyl‐2‐linoleoyl‐sn‐glycero‐3‐phosphocholine‐d₆₂

Abstract

Herein, we report a gram-scale synthesis of perdeuterated linoleic acid-d 31 . The starting materials for the synthesis are two saturated fatty acids, azelaic acid-d 14 and pentanoic acid-d 9 , 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-linoleoylsn-glycero-3-phosphocholine-d 62 (PLPC-d 62 ) is also described. Optimised reaction conditions were developed to access this phospholipid and its regioisomeric purity was characterised by two complementary mass spectrometry techniques.

High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner

“…1,2-dimyristoyl-D54-sn-glycerophosphatidylcholine (d-DMPC, 1,2-dimyristoyl-sn-glycerophosphatidylcholine (DMPC), hydrogenated cholesterol (h-cholesterol, >99%) and 23-(dipyrrometheneboron difluoride)-24-nor-cholesterol (TopFluor® Cholesterol, >99%) were bought from Avanti Polar Lipids. 1-Palmitoyl-d 31 -2-linoleoyl-d 31 -glycerol-3-phosphocholine (d-PLPC) was produced using previously reported methods for the synthesis of mixed acyl glycerophospholipids [19] from palmitic acid-d 31 and linoleic acid-d 31 . 1-Palmitoyl-d 31 - 2-oleoyl-d 33 -glycerol-3-phosphocholine (d-POPC) was produced using previously reported methods for the synthesis of mixed acyl glycerophospholipids [19] from palmitic acid-d 31 and oleic acid-d 33 [20] .…”

“…1-Palmitoyl-d 31 -2-linoleoyl-d 31 -glycerol-3-phosphocholine (d-PLPC) was produced using previously reported methods for the synthesis of mixed acyl glycerophospholipids [19] from palmitic acid-d 31 and linoleic acid-d 31 . 1-Palmitoyl-d 31 - 2-oleoyl-d 33 -glycerol-3-phosphocholine (d-POPC) was produced using previously reported methods for the synthesis of mixed acyl glycerophospholipids [19] from palmitic acid-d 31 and oleic acid-d 33 [20] . Deuterated cholesterol (average 80% D as determined by mass spectrometry, d-cholesterol) was produced using a previously reported method (ca.…”

DGet! An open source deuteration calculator for mass spectrometry data

“…These nuclear properties, its low natural abundance and the similarity of C-H and C-D bonds make deuterated molecules invaluable as a tracers in metabolic studies and as contrast agents in neutron and nuclear magnetic resonance spectroscopic techniques [ 6 – 15 ]. Deuterated molecules can be synthesized using commercially available deuterated precursors (e.g., CD 3 I, CD 3 OD, DCO 2 D, CD 3 NH 2 , LiAlD 4 , NaBD 4 ) in standard chemistry techniques to produce site specific deuterated molecules [ 2 , 16 , 17 ]. Alternatively, deuterium can be incorporated using direct H/D exchange of protonated derivatives in D 2 O using metal catalysts [ 14 , 18 – 23 ], or by biosynthesis using biological organisms grown in D 2 O (Fig.…”

Characterization of the In Vivo Deuteration of Native Phospholipids by Mass Spectrometry Yields Guidelines for Their Regiospecific Customization

“…There have been recent advances in the chemical synthesis of deuterated phospholipids, but doing so on a biomimetic lipidome-wide scale has yet to be achieved. 12 This severely limits the relevance of these model membranes and their use in downstream applications and eliminates them entirely, where in situ measurements are required. There is a growing recognition in the community that natural lipid membranes provide a more native environment for membrane proteins and can greatly impact their stability and activity when purified.…”

“…Generally, only two or three synthetic lipids are mixed to form model lipid membranes, which do not approach the actual complexity of even “simple” bacterial membranes. There have been recent advances in the chemical synthesis of deuterated phospholipids, but doing so on a biomimetic lipidome-wide scale has yet to be achieved . This severely limits the relevance of these model membranes and their use in downstream applications and eliminates them entirely, where in situ measurements are required.…”