Production of specifically deuterium labelled dioleoyl phospholipid species in gram quantities: A convenient synthesis of [C[ 11- 2H 2]oleic acid

Abstract

A relatively straightforward large scale (gram quantity) synthesis of oleic acid specifically labelled with deuterium ( 2H) at the 11 position ([C 11 −2H 2]oleic acid) is described. This synthesis is a modified version of the procedure of Tucker et al. (J. Labelled Compd., 7(1971)137) and involves the coupling of [C 2 −2H 2] nonanal with methyl 9-chlorononanoate via a Wittig reaction. The 2H-labelled nonanal is produced in greater than 75% yield. The coupling reaction results in a 60–70% yield (based on the aldehyde) which contains 95% of the cis (oleic acid) isomer. The subsequent synthesis of 1,2-[C 11 −2H 2] dioleoyl- sn-glycero-3-phosphorylcholine ([C 11 −2H 2]DOPC) yields a compound which exhibits a convenient −2H-NMR quadrupolar splitting (∼ 6 KHz at 20°C). Similarly labelled dioleoyl species of phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG) and phosphatidic acid (PA) are easily derived from the [C 11- 2H 2]DOPC. The dioleoyl phosphatidylethanolamine ([C 11- 2H 2]DOPE) shows similar bilayer to hexagonal (H 11) transition characteristics as unlabelled DOPE, and this transition can be conveniently monitored by 2H-NMR techniques.