{"title":"Unlocking nature's antioxidants: a novel method for synthesising plasmalogens.","authors":"Jay Tromans, Bian Zhang, Bernard T Golding","doi":"10.1039/d4ob01233j","DOIUrl":null,"url":null,"abstract":"<p><p>Plasmalogens are glycerophospholipids distinguished by their <i>O</i>-(<i>Z</i>)-vinyl ether at the <i>sn</i>-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 <i>O</i>-protecting group 1,4-dimethoxynaphthyl-2-methyl ('DIMON') and a new stereospecific method for accessing <i>Z</i>-vinyl ethers, a reproducible, versatile synthetic route to plasmalogens [plasmenyl phosphocholines] has been developed. A key intermediate is (<i>S</i>,<i>Z</i>)-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% <i>Z</i>) and optical purity (>99% <i>ee</i>), including the ability to incorporate polyunsaturated fatty acyl chains (<i>e.g.</i> all <i>Z</i> docosahexaenoic acid) reliably at the <i>sn</i>-2 position.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic & Biomolecular Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1039/d4ob01233j","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
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.