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- MakaleYalnız künye2022Scopus SJRQ3Gram-scale synthesis of (S)-1-(thiophen-2-yl)ethanol in high enantiomeric purity under Enterococcus faecium BY48 biocatalysts
Şahin, Engin
Sulfur-containing chiral heterocyclic secondary alcohols are relevant intermediates in the preparation of enantiomerically pure compounds endowed with biological activity. In this report, we evaluated the reductive potential of different lactic acid bacteria as whole-cell biocatalysts of the enantioselective reduction of 1-(thiophen-2-yl)ethanone (1). Enterococcus faecium BY48, isolated from boza, a cereal-based fermented beverage, was found to be the best biocatalyst in our initial investigations. Using whole-cell preparations of E. faecium BY48, we then systematically analyzed the reaction parameters (pH, incubation period, agitation speed, and temperature) to optimize the yield, the enantiomeric excess (e. e.), and the conversion leading to (S)-1-(thiophen-2-yl)ethanol [(S)-2]. The target derivative, which is a precursor in the synthesis of biologically active chiral compounds, was obtained in enantiomerically pure form, gram-scale amounts, and high yield. This is also the first report that the manufacture of (S)-2 in excellent conversion, yield, enantiopure form, and gram scale used whole-cell biocatalyst. This whole-cell E. faecium BY48 biocatalyzed reaction is a clean, environmentally friendly, and cost-effective process, representing a valuable alternative to chemical catalysis or previously reported biocatalytic procedures in the preparation of (S)-2.
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İncele - MakaleYalnız künye2021Scopus SJRQ3Biocatalytic asymmetric synthesis of (R)-1-tetralol using Lactobacillus paracasei BD101
Kalay, Erbay; Şahin, Engin
Asymmetric bioreduction of ketones is a fundamental process in the production of organic molecules. Compounds containing tetralone rings are found in the structure of many biologically active and pharmaceutical molecules. Biocatalytic reduction of ketones is one of the most promising and significant routes to prepare optically active alcohols. In this study, the reductive capacity of Lactobacillus paracasei BD101 was investigated as whole-cell biocatalyst in the enantioselective reduction of 1-tetralone (1). In biocatalytic reduction reactions, the conversion of the substrate and the enantiomeric excess (ee) of the product are significantly affected by optimization parameters such as temperature, agitation rate, pH, and incubation time. Effects of these parameters on ee and conversion were investigated comprehensively. (R)-1-tetralol ((R)-2), which can be used to treat disorder such as obsessive compulsive, post-traumatic stress, premenstrual dysphoric, and social anxiety, was manufactured in enantiopure form, high yield and gram-scale, using whole-cell biocatalysts of L. paracasei BD101. The 7.04 g of (R)-2 was obtained in optically pure form with 95% yield. Also, to our knowledge, this is the first report on production of (R)-2 using whole-cell biocatalyst in excellent yield, conversion, enantiopure form and gram scale. This is a clean, eco-friendly and cheap method for the synthesis of (R)-2 compared with chemical catalyst.
AtıfScopus23WoS23OpenAlex24İncele - MakaleAçık Erişim2020MACHINE LEARNING APPLICATION FOR OPTIMIZING ASYMMETRICAL REDUCTION OF ACETOPHENONE EMPLOYING COMPLETE CELL OF LACTOBACILLUS SENMAIZUKE AS AN ENVIRONMENTALLY FRIENDLY APPROACH
Taylan, Osman; Yilmaz, Mustafa Tahsin; Balubaid, Mohammed; Alamoudi, Rami; El-Obeid, Tahra; Dertli, Enes; Şahin, Engin; Bakhsh, Ahmed; Herrera-Viedma, Enrique
Recently, optimization of the bioreduction reactions by optimization methodologies has gained special interest as these reactions are affected by several extrinsic factors that should be optimized for higher yields. An important example for these kinds of reactions is the complete cell implications for the bioreduction of prochiral ketones in which the culture parameters play crucial roles. Such biocatalysts provide environmentally friendly and clean methodology to perform reactions under mild conditions with high conversion rates. In the present work, at the first step the Lactobacillus senmaizuke was isolated from sourdough and the complete cell application of Lactobacillus senmaizuke for the bioreduction of acetophenone was optimized by an Artificial Neural networks (ANNs) to achieve the highest enantiomeric excess (EE, %). The culture parameters, pH, temperature, incubation period and agitation speed were the experimental factors that were optimized to maximize EE (%) by machine learning algorithm of Artificial Intelligence modeling and the best conditions to maximize EE (95.5 %) were calculated to be pH of 5.7, temperature of 35 ºC, incubation period of 76 h and agitation speed of 240 rpm with very low sum of squared error value (0.611236 %) to bioreduce acetophenone using complete cell of Lactobacillus senmaizuke as a sourdough isolate GRAS microbial species. Accordingly, The ANN was employed to correctly establish the enantiomeric excess values of the specimen with an average absolute error 0.080739 %.
AtıfScopus3WoS2OpenAlex2İncele - MakaleYalnız künye2020Scopus SJRQ4Candida zeylanoides as whole-cell biocatalyst to perform asymmetric bioreduction of benzophenone derivatives
Şahin, Engin
Candida zeylanoides P1 was investigated as whole cell biocatalyst for the bioreduction of biaryl prochiral ketones into chiral carbinols, which can be used as pharmaceutical intermediate. Bioreduction of different biaryl ketones was carried out to their corresponding chiral biaryl carbinols such as (S)-(4-chlorophenyl) (phenyl) methanol (2a), which can be used in the synthesis of L-cloperastine drug, with antitussive, antiepidemic activity and bronchial musculature relaxant characteristics, in gram scale, enantiopure form (>99%) and excellent yields. The selectivity of C. zeylanoides P1 in enantioselective reduction of biaryl ketones was not affected by the steric and electronic effects of substrates. The current method demonstrates an encouraging green chemistry approach for the production of biaryl secondary chiral alcohols of pharmaceutical importance in mild, inexpensive and environmentally friendly process. The present study has many benefits since this yeast biocatalyst were successfully applied bioreduction of structurally bulky prochiral substrates, which cannot be reducted by chemical catalysis.
AtıfScopus10WoS9OpenAlex10İncele - MakaleYalnız künye2020Scopus SJRQ3First green synthesis of (R)-2-methyl-1-phenylpropan-1-ol using whole-cell Lactobacillus paracasei BD101 biotransformation
Şahin, Engin
Green chemistry includes a novel process in the production of drugs precursors and biological active molecules using biocatalysts, so reducing the threats for human sanitary and ecological pollutions. Asymmetric bioreduction of prochiral ketones by biocatalysts is one of the best prevalent used methods in synthetic organic chemistry due to the production of enantiopure chiral carbinols. This study emphasizes the application biocatalyst L paracasei BD101 for enantioselective bioreduction of 2-methyl-1-phenylpropan-1-one ketone, which contain branched alkyl chain, to (R)-2-methyl-1-phenylpropan-1-ol ((R)-2) in high yields and excellent enantiomeric excess (>99%). The scale-up production was performed, and 4.61 g of (R)-2 in enantiopure form was synthesized. L paracasei BD101 was proved to be a substantial biocatalyst in asymmetric bioreduction of a ketone which contains a branched alkyl chain. There is not any work in the literature similar to our study. Hence, it is important to work on filling this gap. This study is the first example for an enantiopure synthesis of (R)-2 by a biocatalyst. The new green method was developed for bioreduction of bulky ketones, which contains a branched alkyl chain, and it approves the synthesis of novel chiral carbinols in an easy, cheap, and environmentally friendly condition using L paracasei BD101.
AtıfScopus10WoS9OpenAlex10İncele - MakaleAçık Erişim2020Scopus SJRQ3Synthesis of enantiopure (S)-6-chlorochroman-4-ol using whole-cell Lactobacillus paracasei biotransformation
Şahin, Engin
Chromane, which has a fused cyclic structure, is a significant molecule that can be found in the structure of many important compounds. Lactobacillus paracasei BD101 was demonstrated as whole-cell biocatalyst for the synthesis of (S)-6-chlorochroman-4-ol with immense enantioselectivity. The conditions of asymmetric reduction were optimized one factor by one factor using L paracasei BD101 to achieve enantiomerically pure product and complete conversion. Using these obtained optimization conditions, asymmetric reduction of 6-chlorochroman-4-one was performed under environmentally friendly conditions; 6-chlorochroman-4-one, having a fused cyclic structure as previously noted to be difficult to asymmetric reduction with biocatalysts, was enantiomerically reduced to (S)-6-chlorochroman-4-ol with an enantiomeric excess >99% on a high gram scale. This study is the first example in the literature for the enantiopure synthesis of (S)-6-chlorochroman-4-ol using a biocatalyst. Also notably, the optical purity of (S)-6-chlorochroman-4-ol obtained in this study through asymmetric bioreduction using whole-cell biocatalyst is the highest value in the literature. In this study, (S)-6-chlorochroman-4-ol was produced on a gram scale by an easy, inexpensive, and environmentally friendly method, which has shown the production of valuable chiral precursors for drug synthesis and other industrial applications. This study provides a convenient method for the production of (S)-6-chlorochroman-4-ol, which can meet the industrial green production demand of this chiral secondary alcohol.
AtıfScopus23WoS23OpenAlex24İncele - MakaleAçık Erişim2019Scopus SJRQ3Green synthesis of enantiopure (S)-1-(benzofuran-2-yl)ethanol by whole-cell biocatalyst
Şahin, Engin
Optically active aromatic alcohols are valuable chiral building blocks of many natural products and chiral drugs. Lactobacillus paracasei BD87E6, which was isolated from a cereal-based fermented beverage, was shown as a biocatalyst for the bioreduction of 1-(benzofuran-2-yl) ethanone to (S)-1-(benzofuran-2-yl) ethanol with highly stereoselectivity. The bioreduction conditions were optimized using L. paracasei BD87E6 to obtain high enantiomeric excess (ee) and conversion. After optimization of the bioreduction conditions, it was shown that the bioreduction of 1-(benzofuran-2-yl)ethanone was performed in mild reaction conditions. The asymmetric bioreduction of the 1-(benzofuran-2-yl)ethanone had reached 92% yield with ee of higher than 99.9% at 6.73 g of substrate. Our study gave the first example for enantiopure production of (S)-1-(benzofuran-2-yl)ethanol by a biological green method. This process is also scalable and has potential in application. In this study, a basic and novel whole-cell mediated biocatalytic method was performed for the enantiopure production of (S)-1-(benzofuran-2-yl)ethanol in the aqueous medium, which empowered the synthesis of a precious chiral intermediary process to be converted into a sophisticated molecule for drug production.
AtıfScopus32WoS30OpenAlex34İncele - MakaleAçık Erişim2019Scopus SJRQ3Production of enantiomerically pure (S)-phenyl(pyridin-2-yl)methanol with Lactobacillus paracasei BD101
Şahin, Engin; Serencam, Hüseyin; Dertli, Enes
Asymmetric reduction studies of heteroaryl ketones, including phenyl(pyridin-2-yl)methanone in enantioselective form with biocatalysts are very few, and chiral heteroaryl alcohols have been synthesized generally in the small scale. In this study, seven bacterial strains have been used to produce the (S)-phenyl(pyridin-2-yl)methanol in high enantiomeric excess and yield. Among the tested strains, Lactobacillus paracasei BD101, was found to be the best biocatalyst for the reducing phenyl(pyridin-2-yl)methanone to the (S)-phenyl(pyridin-2-yl)methanol at gram scale. The asymmetric bioreduction conditions were systematically optimized using L. paracasei BD101, which demonstrated excellent enantioselectivity and high level of conversion for the bioreduction reaction. (S)-phenyl(pyridin-2-yl)methanol, which is an analgesic, was produced enantiomerically pure form in the first time on gram scale using a biocatalyst. In total, 5.857 g of (S)-phenyl(pyridin-2-yl)methanol in enantiomerically pure form (>99% enantiomeric excess) was obtained in 52 h with 93% yield using whole cells of L. paracasei BD101. Enantiomerically pure (S)-phenyl (pyridin-2-yl)methanol, which is an analgesic, was first produced in the gram scale using a biocatalyst with excellent ee (>99%) and yield (93%).
AtıfScopus9WoS7OpenAlex9İncele - MakaleAçık Erişim2018Scopus SJRQ2Synthesis of Enantiomerically Enriched Drug Precursors by Lactobacillus paracasei BD87E6 as a Biocatalyst
Öksüz, Selda; Şahin, Engin; Dertli, Enes
Global sales of single enantiomeric drug products are growing at an alarming rate every year. A total of 7 bacterial strains were screened for their ability to reduce acetophenones to its corresponding alcohol. Among these strains Lactobacillus paracasei BD87E6 was found to be the most successful biocatalyst to reduce the ketones to the corresponding alcohols. The reaction conditions were systematically optimized for the reducing agent Lactobacillus paracasei BD87E6, which showed high enantioselectivity and conversion for the bioreduction. The preparative scale asymmetric reduction of 3-methoxyacetophenone (1h) by Lactobacillus paracasei BD87E6 gave (R)-1-(3-methoxyphenyl)ethanol (2h) with 92% yield and 99% enantiomeric excess. Compound 2h could be used for the synthesis of (S)-rivastigmine which has a great potential for the treatment of Alzheimer's disease. This study demonstrates that Lactobacillus paracasei BD87E6 can be used as a biocatalyst to obtain chiral carbinol with excellent yield and selectivity. The whole cell catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that Lactobacillus paracasei BD87E6 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest.
AtıfScopus16WoS14OpenAlex15İncele