Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleYalnız künye2022Scopus SJRQ3Biocatalytic asymmetric synthesis of (S)-1-indanol using Lactobacillus paracasei BD71
Kalay, Erbay; Dertli, Enes; Şahin, Engin
Enantiopure benzo-fused cyclic alcohols have been used as a building block of a drug for Parkinson’s disease. 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 seven lactic acid bacteria (LAB) strains were investigated as whole-cell biocatalyst in the enantioselective reduction of 1-indanone (1). Lactobacillus paracasei BD71 was found to have the best reductive capacity. Effects of different parameters such as pH, incubation time, agitation speed and temperature, on enantiomeric excess (ee) and conversion were investigated in a bioconversion. (S)-1-indanol ((S)-2) could be used as precursor for the synthesis of rasagiline mesylate TVP1012 for the therapy of Parkinson’s illness. It was produced in gram-scale (5.24 g), high yield (93%) and enantiomerically pure form using L. paracasei BD71 whole-cell biocatalysts. Also, to our knowledge, this is the first report on production of (S)-2 using whole-cell catalyst in enantiopure form, excellent yield, conversion and gram scale. This is a cheap, clean and eco-friendly process for production of (S)-2 compared to chemical processes.
AtıfScopus6WoS6OpenAlex6
İncele - MakaleYalnız künye2022Scopus SJRQ3Optimization of asymmetric reduction conditions of 1-(benzo [d] [1,3] dioxol-5-yl) ethanone by Lactobacillus fermentum P1 using D-optimal experimental design-based model
Özdemir, Akın; Dertli, Enes; Şahin, Engin
The biocatalytic asymmetric reduction of prochiral ketones is a significant transformation in organic chemistry as chiral carbinols are biologically active molecules and may be used as precursors of many drugs. In this study, the bioreduction of 1-(benzo [d] [1,3] dioxol-5-yl) ethanone for the production of enantiomerically pure (S)-1-(1,3-benzodioxal-5-yl) ethanol was investigated using freeze-dried whole-cell of Lactobacillus fermentum P1 and the reduction conditions was optimized with a D-optimal experimental design-based optimization methodology. This is the first study using this optimization methodology in a biocatalytic asymmetric reduction. Using D-optimal experimental design-based optimization, optimum reaction conditions were predicted as pH 6.20, temperature 30 °C, incubation time 30 h, and agitation speed 193 rpm. For these operating conditions, it was estimated that the product could be obtained with 94% enantiomeric excess (ee) and 95% conversion rate (cr). Besides, the actual ee and cr were found to be 99% tested under optimized reaction conditions. These findings demonstrated that L. fermentum P1 as an effective biocatalyst to obtain (S)-1-(1,3-benzodioxal-5-yl) ethanol and with the D-optimal experimental design-based optimization, this product could be obtained with the 99% ee and 99% cr. Finally, the proposed mathematical optimization technique showed the applicability of the obtained results for asymmetric reduction reactions.
AtıfScopus6WoS6OpenAlex7
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 Erişim2021Scopus SJRQ3Asymmetric reduction of prochiral aromatic and hetero aromatic ketones using whole-cell of Lactobacillus senmaizukei biocatalyst
Çolak, Nida Sezin; Kalay, Erbay; Şahin, Engin
Asymmetric bioreduction of aromatic and heteroaromatic ketones is an important process in the production of precursors of biologically active molecules. In this study, the bioreduction of aromatic and hetero aromatic prochiral ketones into optically active alcohols was investigated using Lactobacillus senmaizukei as a whole-cell catalyst, since whole-cells are less expensive than pure enzymes. The study indicates enantioselective bioreduction of various substituted aromatic ketones (1–16) to the corresponding (R)-and (S)-chiral secondary alcohols (1a–16a) in low to excellent enantioselectivity (6–94%) with good yields (58–95%). In addition, heteroaromatic prochiral ketones 1-(pyridin-2-yl)ethanone (17) and 1-(furan-2-yl)ethanone (18) were reduced to (R)-17a and (R)-18a in enantiopure form with excellent conversion (>99%) and yields. These findings show that L. senmaizukei is a very important biocatalyst for asymmetric reduction of both 6-membered and 5-member heteroaromatic methyl ketones. This method promising a green synthesis for the synthesis of biologically important secondary chiral alcohols in an environmentally friendly and inexpensive process.
AtıfScopus20WoS20OpenAlex19İncele - MakaleYalnız künye2021Scopus SJRQ3Regioselective asymmetric bioreduction of trans-4-phenylbut-3-en-2-one by whole-cell of Weissella cibaria N9 biocatalyst
Kalay, Erbay; Şahin, Engin
There is a considerable interest in the asymmetric production of chiral allylic alcohols, the main building blocks of many functional molecules. The asymmetric reduction of α,β-unsaturated ketones is difficult with traditional chemical protocols in a regioselective and stereoselective manner. In this study, the reductive capacity of whole cell of Leuconostoc mesenteroides N6, Weissella paramesenteroides N7, Weissella cibaria N9, and Leuconostoc pseudomesenteroides N13 was investigated as whole-cell biocatalysts in the enantioselective reduction of (E)-4-phenylbut-3-en-2-one (1). The biocatalytic reduction of 1 to (S,E)-4-phenylbut-3-en-2-ol ((S,E)-2) using the whole cell of W. cibaria N9 isolated from Turkish sourdough was developed in a regioselective fashion, occurring with excellent conversion and recovering the product in good yield. 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. In addition, to our knowledge, this is the first report on production of (S,E)-2 using whole-cell biocatalyst in excellent yield, conversion with enantiopure form and at gram scale. These findings pave the way for the use of whole cell of W. cibaria N9 for challenging higher substrate concentrations of different α,β-unsaturated ketones for regioselective reduction at industrial scale.
AtıfScopus21WoS21OpenAlex23İncele - MakaleYalnız künye2021Scopus SJRQ2Asymmetric reduction of aromatic heterocyclic ketones with bio-based catalyst Lactobacillus kefiri P2
Baydaş, Yasemin; Kalay, Erbay; Şahin, Engin
Abstract: Chiral heterocyclic secondary alcohols have received much attention due to their widespread use in pharmaceutical intermediates. In this study, Lactobacillus kefiri P2 biocatalysts isolated from traditional dairy products, were used to catalyze the asymmetric reduction of prochiral ketones to chiral secondary alcohols. Secondary chiral carbinols were obtained by asymmetric bioreduction of different prochiral substrates with results up to > 99% enantiomeric excess (ee). (R)-1-(benzofuran-2-yl)ethanol 5a, which can be used in the synthesis of pharmaceuticals such as bufuralols potent nonselective β-blockers antagonists, Amiodarone (cardiac anti-arrhythmic), and Benziodarone (coronary vasodilator), was produced in gram-scale, high yield and enantiomerically pure form using L. kefiri P2 biocatalysts. The gram-scale production was carried out, and 9.70 g of (R)-5a in enantiomerically pure form was obtained in 96% yield. Also, production of (R)-5a in terms of yield and gram scale through catalytic asymmetric reduction using the biocatalyst was the highest report so far. This is a cost-effective, clean and eco-friendly process for the preparation of chiral secondary alcohols compared to chemical processes. From an environmental and economic perspective, this biocatalytic method has great application potential, making it a green and sustainable way of synthesis. Graphical Abstract: [Figure not available: see fulltext.]
AtıfScopus8WoS8OpenAlex9İncele - MakaleAçık Erişim2020Scopus SJRQ3Bio-catalytic asymmetric synthesis of β-adrenergic receptor blocker precursor: (R)-2-bromo-1-(naphthalen-2-yl)ethanol
Taşdemir, Volkan; Kalay, Erbay; Dertli, Enes; Şahin, Engin
Aromatic α-halohydrins, particularly 2-haloethanols as significant precursor of drugs, can easily be converted to chiral β-adrenergic receptor blockers. Eight strains of Lactobacillus curvatus were tested as biocatalysts for asymmetric reduction of 2-bromo-1-(naphthalen-2-yl)ethanone 1 to 2-bromo-1- (naphthalen-2-yl) ethanol 2. The parameters of the bioreduction were optimized using L. curvatus N4, the best biocatalyst found. As a result, (R)-2-bromo-1-(naphthalen-2-yl)ethanol 2, which can be β-adrenergic receptor blocker precursor, was produced for the first time in high yield and enantiomerically pure form using biocatalysts. Moreover, the gram scale synthesis was performed and 7.54 g of (R)-2 was synthesized as enantiopure form (enantiomeric excess >99%) in 48 h. The important advantages of this process are that it produces of (R)-2 for the first time in enantiopure form, in excellent yield and under environmentally friendly and moderate reaction conditions. This system is of the potential to be applied at a commercial scale.
AtıfScopus2WoS2OpenAlex2İncele - 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 SJRQ4Production of enantiopure chiral aryl heteroaryl carbinols using whole‐cell Lactobacillus paracasei biotransformation
Şahin, Engin
Aryl and heteroaryl chiral carbinols are useful precursors in the synthesis of drugs. Lactobacillus paracasei BD87E6, which is obtained from a cereal based fermented beverage, was investigated as whole cell biocatalyst for the bioreduction of different ketones (including aromatic, hetero-aromatic and fused bicyclic ketone) into chiral carbinols, which can be used as a pharmaceutical intermediate. The study shows that bioreduction of aryl, heteroaryl and fused bicyclic ketone (1–5) to their corresponding chiral carbinols (1a–5a) in excellent enantioselectivity (>99%) with high yields. This study gave the first example for an enantiopure production of (S)-6-chlorochroman-4-ol (3a), which has many antioxidant activity, by a biological method. For asymmetric bioreduction of other prochiral ketones, these results open way to use of L. paracasei BD87E6 as biocatalysts. Also, the present process shows a hopeful and alternative green synthesis for the production of enantiopure carbinols in a mild, inexpensive and environmentally friendly process.
AtıfScopus21WoS18OpenAlex20İncele - 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 - MakaleYalnız künye2020Scopus SJRQ4Green synthesis of chiral aromatic alcohols with Lactobacillus kefiri P2 as a novel biocatalyst
Baydaş, Yasemin; Dertli, Enes; Şahin, Engin
Biocatalytic reduction is a very important field of research in synthetic organic chemistry. Herein, three different Lactic Acid Bacteria (LAB) strains were evaluated for their bioreduction potential using acetophenone as a model substrate. Among these strains, Lactobacillus kefiri P2 strain was determined as the best asymmetric reduction biocatalyst. Reaction optimization parameters such as reaction time, temperature, agitation speed and pH were systematically optimized using Lactobacillus kefiri P2 strain and model substrate acetophenone. Under these optimized reaction conditions, secondary chiral alcohols were obtained by bioreduction of various prochiral ketones with results up to 99% enantiomeric excess. In addition, the steric and electronic effects of substituents on enantioselectivity and conversion were evaluated. It has been shown that Lactobacillus kefiri P2 biocatalyst was an effective catalyst for asymmetric reduction. This method provides an environmentally friendly method for the synthesis of optically pure alcohols and an alternative approach to chemical catalysts.
AtıfScopus24WoS22OpenAlex22İncele - 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 - MakaleYalnız künye2019Scopus SJRQ3Response surface methodology as optimization strategy for asymmetric bioreduction of acetophenone using whole cell of Lactobacillus senmaizukei
Çolak, Nida Sezin; Şahin, Engin; Dertli, Enes; Yilmaz, Mustafa Tahsin; Taylan, Osman
Whole cell applications are one of the main methodologies for the bioreduction of prochiral ketones to obtain enantiomerically rich chiral secondary alcohols which are mainly affected by the culture parameters of the whole cell. In this study, whole cell of Lactobacillus senmaizukei as a safe Lactic Acid Bacteria (LAB) was used for the reduction of acetophenone and Response Surface Methodology (RSM) application was used to optimize the culture parameters in terms of temperature, pH, incubation time, and agitation level to obtain the highest enantiomeric excess (ee) and conversion rate. The predicted optimum conditions for the bioreduction with whole cell Lactobacillus senmaizukei were found to be pH of 5.25, temperature of 25 °C, incubation time of 72 hr, and agitation level of 100 rpm. Importantly, the efficiency of the reduction of the acetophenone was significantly affected by the linear and quadratic effects of culture parameters. These findings are important to show the role of culture parameters for the bioreduction reactions and also the efficiency of the RSM technique to optimize these parameters.
AtıfScopus10WoS10OpenAlex11İncele - MakaleAçık Erişim2019Scopus SJRQ2Preparation of gentiobiose-derived oligosaccharides by glucansucrase E81 and determination of prebiotic and immune-modulatory functions
İspirli, Hümeyra; Colquhoun, Ian J.; Şahin, Engin; Sagdic, Osman; Dertli, Enes
Gentiobiose-derived oligosaccharides were synthesized by the acceptor reaction of glucansucrase E81 obtained from Lactobacillus reuteri E81 with sucrose and gentiobiose as donor-acceptor sugars, respectively. The reaction products were monitored by TLC analysis and gentiobiose-derived oligosaccharides up to DP 8 were formed during the acceptor reaction as determined by ESI-MS/MS analysis. The glycosylation of the gentiobiose with α-(1 → 6) linkages and α-(1 → 3) linkages was shown by 1H and 13C NMR analysis confirming the structure of these gentiobiose-derived oligosaccharides. The in vitro prebiotic function of the oligosaccharides was determined in which probiotic strains were stimulated whereas no growth was observed in pathogen strains. Gentiobiose-derived oligosaccharides showed immune-modulatory functions in vitro and triggered the production of IL-4, IL12 and TNF-α cytokines in HT29 cells in a dose dependent manner. This study showed the production and functional characterisation of gentiobiose-derived oligosaccharides establishing a promising avenue for future applications.
AtıfScopus26WoS21OpenAlex22İncele - MakaleYalnız künye2019Scopus SJRQ3Biocatalyzed Enantiomerically Pure Production of (S)-Phenyl(thiophen-2-yl)methanol
Şahin, Engin; Dertli, Enes
Chiral aryl heteroaryl methanols are important precursors for the synthesis of pharmaceutically important molecules. The aims of this study were to use a biocatalyst that could efficiently bioreduce phenyl(thiophen2- yl) methanone 1 to (S)-phenyl(thiophen-2-yl) methanol 2, to identify the impact of the physicochemical factors that might affect the bioreduction by the biocatalyst, and to obtain multigram production of aryl heteroaryl secondary alcohol 2 with the biocatalyst under optimized conditions. Over the years, the (S)phenyl( thiophen-2-yl) methanol was synthesized on a small scale using a chemical catalyst without its enantiomerically pure form. In this study, Lactobacillus paracasei BD101 was used for the asymmetric reduction of phenyl(thiophen-2-yl) methanone to (S)-phenyl(thiophen-2-yl) methanol in the large-scale production. The asymmetric bioreduction conditions were systematically optimized, and the production of 3.77 g of (S)-phenyl(thiophen-2-yl) methanol was carried out in enantiomerically pure form > 99% enantiomeric excess (ee), > 99% conversion, and 90% yield. This method obtained with this biocatalyst is a process that can be used industrially in terms of conversion, ee, and yield. This study provides guidance for the application of L. paracasei BD101 in the production of optically active aryl heteroaryl alcohols.
AtıfScopus12WoS12OpenAlex12İncele - 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 - MakaleYalnız künye2019Scopus SJRQ3Synthesis and Biological Evaluation of Novel Tricyclic Pyrrolidinyl (R)-Alcohols and Amines
Şahin, Engin; Kılıç, Hamdullah; Törnük, Fatih; Dertli, Enes
Three new tricyclic pyrrolidinyl alcohols and three tricyclic pyrrolidinyl amines were synthesized, and the antibacterial activities of these compounds were tested against Salmonella enterica subsp. enterica serovar Typhimurium, Escherichia coli O157:H7, Staphylococcus aureus, and Listeria monocytogenes. All tested pyrrolidinyl alcohols and amines showed antibacterial activity to the tested pathogens, but this activity was dependent on the final concentration of the tested compound, and the structure of these compounds were also important for this antibacterial activity. Of the tested compounds, (2R)-2-(octahydro-4,8-ethanocyclohepta[c] pyrrol2(1H)-yl)-2-phenylethanamine (2c) was the most effective compound among the tested pyrrolidinyl alcohols and amines. This study shows a good example of finding new antimicrobials in order to control pathogenic bacteria.
AtıfScopus1WoS1OpenAlex1İncele - MakaleAçık Erişim2019Scopus SJRQ3Whole cell application of Lactobacillus paracasei BD101 to produce enantiomerically pure (S)-cyclohexyl(phenyl)methanol
Şahin, Engin; Serencam, Hüseyin; Dertli, Enes
In this study, a total of 10 bacterial strains were screened for their ability to reduce cyclohexyl(phenyl)methanone 1 to its corresponding alcohol. Among these strains, Lactobacillus paracasei BD101 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 L paracasei BD101, which showed high enantioselectivity and conversion for the bioreduction. The preparative scale asymmetric reduction of cyclohexyl(phenyl)methanone (1) by L paracasei BD101 gave (S)-cyclohexyl(phenyl)methanol (2) with 92% yield and >99% enantiomeric excess. The preparative scale study was carried out, and a total of 5.602 g of (S)-cyclohexyl(phenyl)methanol in high enantiomerically pure form (>99% enantiomeric excess) was produced. L paracasei BD101 has been shown to be an important biocatalyst in asymmetric reduction of bulky substrates. This study demonstrates the first example of the effective synthesis of (S)-cyclohexyl(phenyl)methanol by the L paracasei BD101 as a biocatalyst in preparative scale.
AtıfScopus39WoS37İncele