{"title":"Lipase mediated new chemo-enzymatic synthesis of (RS)-, (R)-, and (S)-bunolol","authors":"Ravinder Reddy Patlolla, Pulivarthi Deepthi, Gajjala Raveena, Khawlhring Rosangzuala, Somarowthu Tejaswini, Reddy Shetty Prakasham, Linga Banoth","doi":"10.1002/chir.23627","DOIUrl":null,"url":null,"abstract":"<p>The β-adrenergic receptor blocking agents are an important class of drug molecules. The present study reports a new chemo and chemo-enzymatic synthetic process for (<i>RS</i>)-, (<i>R</i>)-, and (<i>S</i>)-bunolol, one of the potent β-adrenergic receptor blocker. In chemo-enzymatic process, CAL L4777 lipase was employed for enantioselective kinetic resolution to synthesize the enantiopure (<i>R</i>)-alcohol and (<i>S</i>)-ester from the corresponding racemic alcohol. Thereafter, the corresponding (<i>R</i>)-alcohol and deacylated (<i>S</i>)-ester were treated with <i>tert</i>-butylamine to produce (<i>S</i>)- and (<i>R</i>)-bunolol, respectively. In chemical approach, epichlorohydrin (<i>RS</i>-, <i>R-</i>, and <i>S</i>-) was used as a starting material via respective (<i>RS</i>)-, (<i>S</i>)-, and (<i>R</i>)-glycidyl ether as intermediates for synthesis of enantiomeric (<i>RS</i>)-, (<i>R</i>)-, and (<i>S</i>)-bunolol. In comparison between two approaches, it was found that the chemo-enzymatic process was more effective and resulted in enantiomeric excess of 98% with 35% yield.</p>","PeriodicalId":10170,"journal":{"name":"Chirality","volume":"36 1","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chirality","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/chir.23627","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
Abstract
The β-adrenergic receptor blocking agents are an important class of drug molecules. The present study reports a new chemo and chemo-enzymatic synthetic process for (RS)-, (R)-, and (S)-bunolol, one of the potent β-adrenergic receptor blocker. In chemo-enzymatic process, CAL L4777 lipase was employed for enantioselective kinetic resolution to synthesize the enantiopure (R)-alcohol and (S)-ester from the corresponding racemic alcohol. Thereafter, the corresponding (R)-alcohol and deacylated (S)-ester were treated with tert-butylamine to produce (S)- and (R)-bunolol, respectively. In chemical approach, epichlorohydrin (RS-, R-, and S-) was used as a starting material via respective (RS)-, (S)-, and (R)-glycidyl ether as intermediates for synthesis of enantiomeric (RS)-, (R)-, and (S)-bunolol. In comparison between two approaches, it was found that the chemo-enzymatic process was more effective and resulted in enantiomeric excess of 98% with 35% yield.
期刊介绍:
The main aim of the journal is to publish original contributions of scientific work on the role of chirality in chemistry and biochemistry in respect to biological, chemical, materials, pharmacological, spectroscopic and physical properties.
Papers on the chemistry (physiochemical, preparative synthetic, and analytical), physics, pharmacology, clinical pharmacology, toxicology, and other biological aspects of chiral molecules will be published.