Sachin B. Mulik, Saptarshi Ghosh, Jayeeta Bhaumik, U. Banerjee
{"title":"Biocatalytic synthesis of (S)-Practolol, a selective β-blocker","authors":"Sachin B. Mulik, Saptarshi Ghosh, Jayeeta Bhaumik, U. Banerjee","doi":"10.1515/boca-2015-0006","DOIUrl":null,"url":null,"abstract":"Abstract The present study describes an efficient chemoenzymatic synthesis of enantiopure (S)-Practolol, a selective β-adrenergic receptor blocker. Prior to the synthesis of the target, a synthetic protocol for (RS)-N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide, an essential precursor, was developed. Various commercial lipases were screened for the kinetic resolution of (RS)- N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide using toluene as solvent and vinyl acetate as an acyl donor. Among various lipases screened, Pseudomonas cepacia sol-gel AK showed the highest enantioselectivity (96% enantiomeric excess with 50% conversion), affording (S)-1-(4-acetamidophenoxy)-3-chloropropan-2-yl acetate. Optimization of the reaction parameters was carried out in order to find the best-suited conditions for the biocatalysis. Furthermore, the enantiopure intermediate was hydrolyzed and the resulting product was reacted with isopropylamine to afford (S)-Practolol. This biocatalytic procedure depicts a green technology for the synthesis of (S)-Practolol with better yield and enantiomeric excess.","PeriodicalId":8747,"journal":{"name":"Biocatalysis","volume":"3 1","pages":"130 - 140"},"PeriodicalIF":0.0000,"publicationDate":"2016-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biocatalysis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/boca-2015-0006","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 2
Abstract
Abstract The present study describes an efficient chemoenzymatic synthesis of enantiopure (S)-Practolol, a selective β-adrenergic receptor blocker. Prior to the synthesis of the target, a synthetic protocol for (RS)-N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide, an essential precursor, was developed. Various commercial lipases were screened for the kinetic resolution of (RS)- N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide using toluene as solvent and vinyl acetate as an acyl donor. Among various lipases screened, Pseudomonas cepacia sol-gel AK showed the highest enantioselectivity (96% enantiomeric excess with 50% conversion), affording (S)-1-(4-acetamidophenoxy)-3-chloropropan-2-yl acetate. Optimization of the reaction parameters was carried out in order to find the best-suited conditions for the biocatalysis. Furthermore, the enantiopure intermediate was hydrolyzed and the resulting product was reacted with isopropylamine to afford (S)-Practolol. This biocatalytic procedure depicts a green technology for the synthesis of (S)-Practolol with better yield and enantiomeric excess.
摘要本研究描述了一种高效的化学酶合成对映纯(S)-Practolol,一种选择性β-肾上腺素受体阻滞剂。在合成目标之前,开发了一种重要前体(RS)- n -4-(3-氯-2-羟基丙氧基)苯乙酰胺的合成方案。以甲苯为溶剂,醋酸乙烯为酰基给体,筛选了多种商用脂肪酶对(RS)- N-4-(3-氯-2-羟基丙氧基)苯乙酰胺的动力学分解。在筛选的各种脂肪酶中,洋葱假单胞菌溶胶-凝胶AK表现出最高的对映体选择性(96%的对映体过剩,50%的转化率),提供(S)-1-(4-乙酰氨基苯氧基)-3-氯丙-2-乙酸酯。对反应参数进行了优化,以寻找最适宜的生物催化条件。再将对映纯中间体水解,产物与异丙胺反应生成(S)-普practolol。这一生物催化过程描述了一种绿色合成(S)-Practolol的技术,具有较高的产率和对映体过量。