Unlocking nature's antioxidants: a novel method for synthesising plasmalogens.

Plasmalogens are glycerophospholipids distinguished by their O -( Z )-vinyl ether at the sn -1 position. These lipids are implicated in several disease states requiring analytical, diagnostic and therapeutic interventions, which demand synthetic availability for a variety of structural types. By deploying the new O -protecting group 1,4-dimethoxynaphthyl-2-methyl ('DIMON') and a new stereospecific method for accessing Z -vinyl ethers, a reproducible, versatile synthetic route to plasmalogens [plasmenyl phosphocholines] has been developed. A key intermediate is ( S , Z )-1-((1,4-dimethoxynaphthalen-2-yl)methoxy)-3-(hexadec-1-en-1-yloxy)propan-2-ol, which in principle, permits plasmalogen synthesis 'à la carte' at scale. The methodology compares favourably with all previous synthetic routes by virtue of the very high configurational (>99% Z ) and optical purity (>99% ee ), including the ability to incorporate polyunsaturated fatty acyl chains ( e.g. all Z docosahexaenoic acid) reliably at the sn -2 position.