Sürdürülebilir Kalkınma Amaçları

• 3

• MakaleAçık Erişim2024Scopus SJRQ2/r/bayburt/11764
  Green synthesis of (S)-1-(furan-2-yl)propan-1-ol from asymmetric bioreduction of 1-(furan-2-yl)propan-1-one using whole-cell of Lactobacillus paracasei BD101

  Bülbül, Ali Savaş; Şahin, Engin

  Chiral heterocyclic alcohols are important precursors for production of pharmaceutical medicines and natural products. (S)-1-(furan-2-yl)propan-1-ol ((S)-2) can be used production of pyranone, which can be used in the synthesis of sugar analogues, antibiotics, tirantamycines, and anticancer drugs. The synthetic approaches for (S)-2, however, have substantial difficulties in terms of inadequate enantiomeric excess (ee) and gram scale synthesis. Moreover, the biocatalytic synthesis of (S)-2 is unknown until now. In this study, the synthesis of (S)-2 was carried out by performing the asymmetric bioreduction of 1-(furan-2-yl)propan-1-one (1) using the Lactobacillus paracasei BD101 biocatalyst obtained from boza, a grain-based fermented beverage. (S)-2 was obtained with >99% conversion, >99% ee, and 96% yield under the optimized conditions. Furthermore, in 50 h, 8.37 g of 1 was entirely transformed into (S)-2 on gram scale (96% isolated yield, 8.11 g). This is the first report on the high-gram scale biocatalyzed synthesis of enantiopure (S)-2. These data suggest that L. paracasei BD101 can be used to bioreduction of 1 in gram scale and efficiently produce (S)-2. Furthermore, these findings laid the base for future study into the biocatalytic production of (S)-2. It was particularly notable as it was the highest known to date optical purity of (S)-2 generated by asymmetric reduction using a biocatalyst. This work offers a productive environmentally friendly method for producing (S)-2 using biocatalysts.

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  AtıfScopus10·WoS10·OpenAlex12

  İncele
• MakaleYalnız künye2022Scopus SJRQ3/r/bayburt/13418
  Optimization of asymmetric reduction conditions of 2-bromo-1-(naphthalen-2-yl)ethanone by Enterococcus faecium BY48 biocatalyst with A-optimal design-embedded model

  Özdemir, Akın; Şahin, Engin

  Aromatic α-halohydrins, especially 2-haloethanols, which are a common pharmacological precursor, may be readily transformed to chiral β-adrenergic receptor blockers. Studies including the synthesis of (S)-2-bromo-1-(naphthalen-2-yl)ethanol ((S)-2), an α-halohydrin, in high conversion, enantiomeric excess (ee), and yield by biocatalytic asymmetric reduction of 2-bromo-1-(naphthalen-2-yl)ethanone (1) are still insufficient. Moreover, asymmetric reduction of substrate 1 using a mathematical optimization method is not explored in the current literature. In this article, the four asymmetric bioreduction conditions, which are (1) pH, (2) temperature, (3) incubation period, and (4) agitation speed, of substrate 1 were optimized to obtain (S)-2 with A-optimal design-embedded model in the presence of Enterococcus faecium BY48. Optimum bioreduction conditions were determined by the A-optimal design-embedded model as follows: pH = 7, temperature = 25°C, incubation period = 24 h, and agitation speed = 200 rpm. And then, it was suggested that (S)-2 could be obtained with 98.88% ee and 100% conversion rate (cr) under these optimum conditions. As a result of the experimental reaction performed under the optimization conditions suggested by the model, (S)-2 was obtained with 99% ee and 100% cr. The study revealed that E. faecium BY48 could be used as a biocatalyst in asymmetric reduction reactions. Also, the A-optimal design-embedded model could have the great potential to obtain the optimum asymmetric bioreduction conditions.

  AtıfScopus3·WoS3·OpenAlex4

  İncele
• MakaleYalnız künye2022Scopus SJRQ3/r/bayburt/12198
  Gram-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.

  AtıfScopus3·WoS3·OpenAlex5

  İncele
• MakaleYalnız künye2021Scopus SJRQ3/r/bayburt/13586
  Biocatalytic 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.

  AtıfScopus23·WoS23·OpenAlex24

  İncele
• MakaleYalnız künye2021Scopus SJRQ3/r/bayburt/13414
  Regioselective 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.

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  AtıfScopus21·WoS21·OpenAlex23

  İncele
• MakaleAçık Erişim2020Scopus SJRQ3/r/bayburt/11959
  Synthesis 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.

  AtıfScopus23·WoS23·OpenAlex24

  İncele
• MakaleAçık Erişim2019Scopus SJRQ3/r/bayburt/13299
  Green 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.

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  AtıfScopus32·WoS30·OpenAlex34

  İncele
• MakaleAçık Erişim2019Scopus SJRQ3/r/bayburt/12315
  Whole 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.

  AtıfScopus39·WoS37

  İncele
• MakaleAçık Erişim2018Scopus SJRQ2/r/bayburt/13614
  Production of (R)-1-(1,3-benzodioxol-5-yl)ethanol in high enantiomeric purity by Lactobacillus paracasei BD101

  Şahin, Engin

  Piperonyl ring is found in a number of naturally occurring compounds and possesses enormous biological activities. There are many studies in the literature with compounds containing a piperonyl ring, but there are very few studies on the synthesis of chiral piperonyl carbinol. The objective of this study was to determine the microbial reduction ability of bacterial strains and to reveal the effects of different physicochemical parameters on this reduction ability. A total of 15 bacterial isolates were screened for their ability to reduce 1-(benzo[d][1,3]dioxol-5-yl) ethanone 1 to its corresponding alcohol. Among these isolates Lactobacillus paracasei BD101 was found to be the most successful biocatalyst to reduce the ketone containing piperonyl ring to the corresponding alcohol. 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 study was performed, and a total of 3.72 g of (R)-1-(1,3-benzodioxol-5-yl) ethanol in high enantiomeric form (>99% enantiomeric excess) was produced in a mild, cheap, and environment-friendly process. This study demonstrates that L paracasei BD101 can be used as a biocatalyst to obtain chiral carbinol with excellent yield and selectivity.

  AtıfScopus43·WoS42

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