DSpace Arşivi :: by Yazar "Sahin, Engin" değerine göre listeleniyor

Yazar "Sahin, Engin" seçeneğine göre listele

Listeleniyor 1 - 20 / 27

Asymmetric reduction of aromatic heterocyclic ketones with bio-based catalyst Lactobacillus kefiri P2
(Springer International Publishing Ag, 2021) Baydas, Yasemin; Kalay, Erbay; Sahin, Engin
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 beta-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.
Asymmetric reduction of prochiral aromatic and hetero aromatic ketones using whole-cell of Lactobacillus senmaizukei biocatalyst
(Taylor & Francis Inc, 2021) Colak, Nida Sezin; Kalay, Erbay; Sahin, 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.
Bio-catalytic asymmetric synthesis of ?-adrenergic receptor blocker precursor: (R)-2-bromo-1-(naphthalen-2-yl)ethanol
(Taylor & Francis Ltd, 2020) Tasdemir, Volkan; Kalay, Erbay; Dertli, Enes; Sahin, Engin
Aromatic alpha-halohydrins, particularly 2-haloethanols as significant precursor of drugs, can easily be converted to chiral beta-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 beta-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.
Biocatalytic asymmetric synthesis of (R)-1-tetralol using Lactobacillus paracasei BD101
(Wiley, 2021) Kalay, Erbay; Sahin, 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.
Biocatalytic asymmetric synthesis of (S)-1-indanol using Lactobacillus paracasei BD71
(Taylor & Francis Ltd, 2022) Kalay, Erbay; Dertli, Enes; Sahin, 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.
Design, synthesis, antioxidant and anticholinesterase activities of novel isonicotinic hydrazide-hydrazone derivatives
(Elsevier, 2023) Aslanhan, Ozlem; Kalay, Erbay; Tokali, Feyzi Sinan; Can, Zehra; Sahin, Engin
The design and synthesis of hydrazone derivatives are increasing in popularity day by day due to the significant biological activities of this scaffold. In the present study, twelve novel isonicotinic hydrazide-hydrazone analogues were synthesized by the condensation reaction of isonicotinic hydrazide with ben-zaldehyde possessing sulfonate moiety. The structures of the novel compounds have been characterized in detail using spectroscopic techniques. All compounds have shown inhibitory effects against the AChE en-zyme at rates ranging from 21.00 to 59.48%. Among them, compound 5 has exhibited the best inhibitory effect of 59.48% against AChE at a concentration of 0.1 mM. Furthermore, to determine how effective the novel compounds are as antioxidants, FRAP and DPPH studies were also carried out. FRAP values in compounds 1-12 were found to range from 26.989-3415.556 mu mol FeSO4.7H2O/mg. They also displayed moderate antioxidant potential in the range of SC50= 0.03-87.32 mg/mL compared with the control Trolox (SC50 = 0.004) in DPPH radical scavenging activities. It was seen that the AChE inhibition percentages of the compounds were in the range of 23.04-58.10% at 0.1 mM concentration. This is the first research on the synthesis, antioxidant and enzyme inhibition properties of these compounds. (c) 2023 Elsevier B.V. All rights reserved.
Effective biocatalytic synthesis of enentiopure ( R )-1,2-diphenylethanol as a pharmaceutical precursor using whole-cell biocatalyst
(Elsevier, 2024) Cakmak, Fadile; Ozdemir, Akin; Dertli, Enes; Sahin, Engin
Optically active alcohols are crucial precursors. 1,2-Diarylethanols and their analogues constitute a significant group of substances of biological significance. The biocatalytic synthesis of ( R )-1,2-diphenylethanol ( ( R )-2 ), which can be utilized as a precursor to important drugs, is still not at the desired level in terms of substrate amount and production process. This study asymmetrically reduced 1,2-diphenylethanone (1) using the Lactobacillus paracasei BD87E6 biocatalyst and a novel orthogonal quadratic design -embedded optimization approach. The following reaction optimization conditions were determined using the suggested optimization technique: pH = 6, temperature = 31 C-degrees , incubation period = 48 h, and agitation speed=134 rpm. In addition, the reaction conversion was estimated to be 99.38 %, and the product 's enantiomeric excess (ee) was estimated to be 99.12 %. Further, ( R )-2 was produced with >99 % ee, >99 % conversion, and 98 % yield in the experimental investigation under the established optimum conditions. This study is the first attempt to reduce substrate 1 to (R) or (S)-2 using a mathematical optimization method in the presence of a biocatalyst. Furthermore, on a highgram scale, 1 (15.70 g) was entirely transformed into ( R )-2 (15.54 g, 98 % isolated yield). Notably, this study is also the first to perform the gram -scale production of ( R )-2 using a novel optimization approach and a biocatalyst. Finally, the innovative and novel orthogonal quadratic design -embedded optimization technique has been demonstrated as an efficient, cost-effective, and environmentally friendly biocatalytic procedure for synthesizing ( R )-2 .
Efficient bio-catalytic production of enentiopure (S)-(4-chlorophenyl) (phenyl)methanol as a drug precursor by using a novel rotatable composite design-based optimization strategy
(Elsevier, 2023) Tozlu, Nesrullah; Bulbul, Ali Savas; Ozdemir, Akin; Sahin, Engin
Asymmetric bioreductions catalyzed by biocatalysts have demonstrated great promise in manufacturing chiral alcohols. On the other hand, the synthesis of (S)-(4-chlorophenyl)(phenyl)methanol ((S)-2), precursors of Lcloprastine and carbinoxamine, still presents considerable challenges due to the inadequate substrate quantity and production process. In this work, a novel rotatable composite design-based optimization technique was used with the Lactobacillus paracasei BD101 biocatalyst for the asymmetric reduction of (4-chlorophenyl)(phenyl) methanone (1). Optimization conditions of the reaction were determined by the proposed optimization strategy as: pH=5.85, temperature=37 degrees C, incubation time=71 h, and agitation speed=120 rpm. The reaction conversion and the product of enantiomeric excess (ee) were also predicted to be 97% and 99%, respectively. In the experimental study performed under the determined optimized conditions, (S)-2 was obtained with >99% ee, >99% conversion, and 97% yield. In addition, 1 with the amount of 15.166 g was completely converted to (S)-2 (14.85 g, 97% isolated yield) on a high-gram scale. Notice that the manufacture of (S)-2 on a gram scale utilizing a biocatalyst and an optimization technique is demonstrated in this work for the first time. Finally, an economical, effective, and environmentally friendly biocatalytic process for the biocatalytic synthesis of (S)-2, which have antitussive and antiemetic properties and relax the bronchial muscle, has been demonstrated by the novel rotatable composite design-based optimization method.
Efficient bioreduction of 1-(furan-2-yl)ethanone into enantiomerically pure drug precursor by Lactobacillus paracasei BD101
(Elsevier, 2023) Sahin, Engin
Asymmetric bioreduction catalyzed by biocatalyst have shown considerable potential in the preparation of chiral alcohols. (R)-1-(furan-2-yl)ethanol ((R)-2) can be used precursor in the synthesis of many naturally bioactive piperidine alkaloids such as (-)-Cassine, (-)-Spectaline, (-)-Carnavaline, Prosafrine and (-)-Prosafrinine. Moreover, (R)-2 a key chiral precursor in the production of alpha, beta-unsaturated delta-lactones, which have antifungal, antibiotic, and cytotoxic effects on human tumor cells. However, the synthesis routes of (R)-2 still pose signif-icant challenges in term of unsatisfactory enantiomeric excess (ee) and gram scale synthesis. In this study, Lactobacillus paracasei BD101 biocatalyst from boza, a cereal-based fermented beverage, for the asymmetric bioreduction of the 1-(furan-2-yl)ethanone (1). Following biocatalytic process optimization, (R)-2 was generated with >99% ee and 97% yield. In addition, 9.9 g of 1 was completely converted into (R)-2 on a gram scale (9.78 g, 97% isolated yield) in 48 h. This is the first report about the fabrication of enantiopure (R)-2 in high gram scale using biocatalyst. The optical purity of (R)-2 produced by asymmetric reduction with L paracasei BD101 was also noteworthy since it was the highest documented to date. This study provides an efficient green process for the biocatalytic synthesis of (R)-2.
Efficient bioreduction of 4-phenyl-2-butanone to drug precursor (S)-4-phenyl-2-butanol by a whole-cell biocatalyst using a novel hybrid design technique
(Elsevier, 2024) Bayhan, Beyzanur; Ozdemir, Akin; Dertli, Enes; Sahin, Engin
Asymmetric synthesis is a critical tactic in pharmaceutical industries for creating chiral medications as it allows an enantiomer to be obtained in synthetic chemistry. The asymmetric bioreduction processes by biocatalysts have shown significant potential in producing chiral alcohols. The amount of substrate and the production method of the biocatalytic synthesis of (S)-4-phenyl-2-butanol ((S)-2) are not still desired levels. Furthermore, the biocatalytic asymmetric reduction of 4-phenyl-2-butanone (1) to (R)- or (S)-4-phenyl-2-butanol did not use any mathematical modeling techniques. In this study, the asymmetric bioreduction of 1 was carried out in this work employing Lactobacillus paracasei BD71 biocatalyst and a novel hybrid design-based optimization approach. By using the hybrid design technique, the optimal circumstances were discovered to be pH = 7, temperature = 29 degrees C, incubation period = 66 h, and agitation speed = 189 rpm. Also, the enantiomeric excess (ee) and conversion could be 99.15 % and 98.19 %, respectively. Next, (S)-2 was acquired to be ee: 99 %, conversion: >99 %, and yield: 97 % from the optimum bioreduction conditions. Furthermore, 14.08 g of 1 under optimal conditions was entirely transformed into (S)-2 (13.84 g, 97 % isolated yield). This study is the first research attempt to use a biocatalyst and an innovative and new hybrid design-based optimization approach to fabricate enantiopure (S)-2 at a high gram scale. This work has successfully demonstrated that the new hybrid design-based optimization technique is applicable to biocatalytic asymmetric reduction processes.
Efficient bioreduction of cyclohexyl phenyl ketone by Leuconostoc pseudomesenteroides N13 biocatalyst using a distance-based design-focused optimization model
(Elsevier, 2022) Ozdemir, Akin; Sahin, Engin
Whole-cell biocatalysts have been a popular method for the preparation of chiral alcohols. Although asymmetric reduction of cyclohexyl(phenyl)methanone (1) by chemical catalysts is common, a biocatalytic asymmetric reduction is extremely rare. In this respect, we report herein that Leuconostoc pseudomesenteroides N13 was successfully employed as a biocatalyst to reduce 1 to (S)-cyclohexyl(phenyl)methanol ((S)-2). Furthermore, the use of a mathematical optimization strategy for asymmetric reduction of substrate 1 is not known in the current literature. The new distance-based design-focused optimization model was used to enhance the conversion of the substrate, enantiomeric excess (ee) of product, and yield. The distance-based design-focused optimization model identified the following optimal bioreduction conditions: pH=6.46, temperature=30 degrees C, incubation period=72 hours, and agitation speed=199 rpm. Then it was stated that under these ideal conditions, (S)-2 may be produced with 99 % ee and 98.46 % conversion rate (cr). (S)-2 was achieved with 99% ee, and 99% cr as a consequence of the experimental reaction carried out under the indicated optimization conditions. It has been shown that Leuconostoc pseudomesenteroides N13 can be utilized as a biocatalyst in asymmetric reduction reactions. This study, in addition to being the first example of a bioreduction of substrate 1 by mathematical optimization, also demonstrates for the first time the distance-based design-focused model can be used in the bioreduction reaction.
Gram-scale synthesis of (S)-1-(thiophen-2-yl)ethanol in high enantiomeric purity under Enterococcus faecium BY48 biocatalysts
(Wiley, 2022) Sahin, 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.
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
(Wiley, 2024) Bulbul, Ali Savas; Sahin, 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.
MACHINE LEARNING APPLICATION FOR OPTIMIZING ASYMMETRICAL REDUCTION OF ACETOPHENONE EMPLOYING COMPLETE CELL OF LACTOBACILLUS SENMAIZUKE AS AN ENVIRONMENTALLY FRIENDLY APPROACH
(Health & Environment Assoc, 2020) Taylan, Osman; Yilmaz, Mustafa Tahsin; Balubaid, Mohammed; Alamoudi, Rami; El-Obeid, Tahra; Dertli, Enes; Sahin, Engin
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 degrees C, 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 %.
Modified distance optimization method for the asymmetric bioreduction conditions of phenyl(thiophen-2-yl)methanone by Weissella paramesenteroides N7
(Pergamon-Elsevier Science Ltd, 2023) Ozdemir, Akin; Sahin, Engin
Chirality plays a significant part in life since it is closely linked to carrying out the many metabolic processes that make up a living being. Chiral secondary alcohols such as diaryl-, aryl heteroaryl-, and diheteroaryl are employed in pharmaceuticals as drug intermediates. Although biocatalytic asymmetric reduction of prochiral ketones containing aromatic and heteroaromatic groups is widely known, biocatalytic reduction of heteroaromatic prochiral ketones containing sulfur heteroatoms is rarely known. Very few studies exist in the literature, including the biocatalytic reduction of phenyl(thiophen-2-yl) methanone (1). Moreover, the biocatalytic reduction of 1 with a mathematical modelling and optimization technique is unknown until now. In this study, Weissella paramesenteroides N7 biocatalyst for the asymmetric bioreduction of 1 using a novel modified distance optimization method. Optimization conditions were found as pH = 6.46, temperature = 26 degrees C, incubation period = 71 h, agitation speed = 200 rpm by the modified distance optimization method, and it was determined that the conversion and enantiomeric excess (ee) under these conditions could be 98.7% and 98%, respectively. Under these proposed optimization conditions, (S)-phenyl(thiophen-2-yl)methanol ((S)-2) was obtained with >99% ee, >99% conversion, and 97% yield. In addition, 11.29 g of 1 was completely converted into (S)-2 (11.07 g, 97% isolated yield) under optimized conditions. This is the first report about the fabrication of enantiopure (S)-2 in high gram scale using a biocatalyst and a novel modified distance optimization technique. In this study, the successful applicability of the new modified distance optimization method in biocatalytic asymmetric reduction reactions has been successfully demonstrated. (c) 2023 Elsevier Ltd. All rights reserved.
A Multi-response Nonlinear Programming Model with an Inscribed Design to Optimize Bioreduction Conditions of (S)-phenyl (pyridin-2-yl)methanol by Leuconostoc pseudomesenteroides N13
(Springer Heidelberg, 2024) Ozdemir, Akin; Sahin, Engin
Asymmetric bioreductions have the potential to synthesize chiral alcohols when catalyzed by biocatalysts. Nevertheless, the (S)-phenyl (pyridin-2-yl)methanol ((S)-2) analgesic synthesis poses significant challenges concerning unsatisfactory substrate amount and production method. Thus, this study proposes an inscribed design-focused multi-response nonlinear optimization model for the asymmetric reduction of the phenyl(pyridin-2-yl)methanone (1) with Leuconostoc pseudomesenteroides N13 biocatalyst. From the novel inscribed design-focused multi-response nonlinear optimization model, optimization conditions of the reaction, such as pH = 6, temperature = 29 degrees C, incubation time = 53 h, and agitation speed = 153 rpm, were found. Also, the reaction conversion was predicted to be 99%, and the product of the enantiomeric excess (ee) was 98.4% under the obtained optimization conditions. (S)-2 was obtained with 99% ee, 99% conversion, and 98% yield while performing a validation experiment using the determined optimized conditions. In addition, 1 with the amount of 11.9 g was converted entirely to (S)-2 (11.79 g, 98% isolated yield) on a high gram scale. Also, this study is noted as the first example of the gram-scale production of (S)-2 using an optimization strategy and biocatalyst. Further, the applicability of the inscribed design-focused optimization model in biocatalytic reactions has been demonstrated and provides an effective process for the analgesic synthesis of (S)-2, which is a green, cost-effective method of producing chiral aryl heteroaryl methanol.
Optimization of Asymmetric Bioreduction Conditions of 2-methyl-1-phenylpropan-1-one by Lactobacillus fermentum BY35 Using I-Optimal Design-Based Model
(Springer Heidelberg, 2022) Aksuoglu, Selmani; Ozdemir, Akin; Serencam, Huseyin; Dertli, Enes; Sahin, Engin
The bioreduction of prochiral ketones offers efficient access to chiral secondary alcohols, which are potentially beneficial precursors for producing many biologically active compounds and natural products. This bioreduction process can be affected by different parameters when whole-cell of biocatalysts such as Lactic Acid Bacteria strains are applied. In this context, this paper proposed an I-optimal design-based model to optimize culture parameters such as temperature, pH, incubation period, and agitation speed for asymmetric bioreduction of 2-methyl-1-phenylpropan-1-one (1) with Lactobacillus fermentum BY35 as a biocatalyst while achieving the highest conversion rate (cr) and enantiomeric excess (ee). The optimum settings of the four culture parameters and the cr and ee values were found using the proposed optimization model as follows: pH = 6.5, temperature = 25 degrees C, incubation period = 38.5 h, agitation speed = 200 rpm, the ee value = 98.78%, and the cr value = 98.92%. After the validation of the process, the cr and ee values were found to be > 99% and > 99%, respectively, while using the optimum operating conditions from the optimization model. Thus, the results of the optimization model are consistent with the results of the validation experiment. It is also noted that this paper is the first to optimize culture parameters using the proposed I-optimal design-based model for an asymmetric reduction.
Optimization 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
(Taylor & Francis Inc, 2022) Ozdemir, Akin; Dertli, Enes; Sahin, 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 degrees 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.
Optimization of asymmetric reduction conditions of 2-bromo-1-(naphthalen-2-yl)ethanone by Enterococcus faecium BY48 biocatalyst with A-optimal design-embedded model
(Wiley, 2022) Ozdemir, Akin; Sahin, Engin
Aromatic alpha-halohydrins, especially 2-haloethanols, which are a common pharmacological precursor, may be readily transformed to chiral beta-adrenergic receptor blockers. Studies including the synthesis of (S)-2-bromo-1-(naphthalen-2-yl)ethanol ((S)-2), an alpha-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 degrees 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.
Optimization of Biocatalytic Production of Enantiopure (S)-1-(4-Methoxyphenyl) Ethanol with Lactobacillus senmaizuke Using the Box-Behnken Design-Based Model
(Springer Heidelberg, 2022) Kavi, Mervenur; Ozdemir, Akin; Dertli, Enes; Sahin, Engin
Enantiomerically pure (S)-1-(4-methoxyphenyl) ethanol is a significant molecule for the production of various drug intermediates. (S)-1-(4-methoxyphenyl) ethanol was synthesized from 4-methoxyacetophenone using Lactobacillus senmaizuke as a biocatalyst. In addition, optimization of experimental conditions is important to analyze the role of culture parameters for catalytic bioreduction reactions. For this particular purpose, the experimental conditions of pH, incubation period, temperature, and agitation speed were investigated with the Box-Behnken experimental design-based proposed optimization model. (S)-1-(4-methoxyphenyl) ethanol, which can be used for the synthesis of antihistamines, including diphenhydramine hydrochloride and loratadine cycloalkyl [b] indoles that have the treatment function for an allergic response, was obtained in > 99% conversion, > 99% enantiomeric excess and 96% yield with whole cells of L. senmaizukei at this optimization conditions: pH = 5.80, the temperature = 29 degrees C, incubation period = 50 h, and agitation speed = 155 rpm. The bioreduction of 4-methoxyacetophenone efficiency was importantly affected by the quadratic and linear effects of experimental design parameters. Besides, the results demonstrate the importance of design parameters for catalytic bioreduction reactions. It is also concluded that the results show the effectiveness of the Box-Behnken experimental design-based proposed model to obtain optimum operating conditions of design parameters for catalytic bioreduction reactions.

Yazar "Sahin, Engin" seçeneğine göre listele

Sayfa Başına Sonuç

Sıralama seçenekleri