Lipase mediated new chemo-enzymatic synthesis of (RS)-, (R)-, and (S)-bunolol

IF 2.8 4区 化学 Q2 CHEMISTRY, ANALYTICAL
Chirality Pub Date : 2023-11-13 DOI:10.1002/chir.23627
Ravinder Reddy Patlolla, Pulivarthi Deepthi, Gajjala Raveena, Khawlhring Rosangzuala, Somarowthu Tejaswini, Reddy Shetty Prakasham, Linga Banoth
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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.

Abstract Image

Abstract Image

脂肪酶介导的新型化学酶合成(RS)-, (R)-和(S)-布诺洛尔。
β-肾上腺素能受体阻断剂是一类重要的药物分子。本研究报道了一种新的化学和化学酶合成(RS)-, (R)-和(S)-布诺洛尔的方法,它是一种有效的β-肾上腺素受体阻滞剂。在化学酶催化过程中,利用CAL L4777脂肪酶进行对映选择动力学拆分,由相应的外消旋醇合成对映纯(R)醇和(S)酯。然后用叔丁胺处理相应的(R)-醇和(S)-脱酰基酯,分别得到(S)-和(R)-布诺洛尔。化学方法以环氧氯丙烷(RS-、R-、S-)为原料,分别通过(RS)-、(S)-、(R)-缩水甘油酯醚为中间体,合成对映体(RS)-、(R)-、(S)-布诺洛尔。对比两种方法,发现化学-酶法更有效,对映体含量超过98%,产率达到35%。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Chirality
Chirality 医学-分析化学
CiteScore
4.40
自引率
5.00%
发文量
124
审稿时长
1 months
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.
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