Sürdürülebilir Kalkınma Amaçları
Yazarlar
Yayınlar
- MakaleAçık Erişim2024Scopus SJRQ1Efficient 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
Bayhan, Beyzanur; Özdemir, Akın; Dertli, Enes; Şahin, 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 °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.
AtıfScopus9WoS8OpenAlex5
İncele - MakaleAçık Erişim2024Scopus SJRQ2Green 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.
AtıfScopus10WoS10OpenAlex12
İncele - MakaleYalnız künye2024Scopus SJRQ1Effective biocatalytic synthesis of enentiopure (R)-1,2-diphenylethanol as a pharmaceutical precursor using whole-cell biocatalyst
Çakmak, Fadile; Özdemir, Akın; Dertli, Enes; Şahin, 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, 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 high-gram 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.
AtıfScopus7WoS7OpenAlex6İncele - MakaleYalnız künye2023Scopus SJRQ2Efficient bioreduction of 1-(furan-2-yl)ethanone into enantiomerically pure drug precursor by Lactobacillus paracasei BD101
Şahin, 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 α, β-unsaturated δ- lactones, which have antifungal, antibiotic, and cytotoxic effects on human tumor cells. However, the synthesis routes of (R)-2 still pose significant 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.
AtıfScopus16WoS15OpenAlex14İncele - MakaleAçık Erişim2023Scopus SJRQ2Efficient bio-catalytic production of enentiopure (S)-(4-chlorophenyl)(phenyl)methanol as a drug precursor by using a novel rotatable composite design-based optimization strategy
Tozlu, Nesrullah; Bülbül, Ali Savaş; Özdemir, Akın; Şahin, 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 L-cloprastine 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 °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.
AtıfScopus3WoS3OpenAlex2İncele - MakaleAçık Erişim2022Scopus SJRQ2Efficient bioreduction of cyclohexyl phenyl ketone by Leuconostoc pseudomesenteroides N13 biocatalyst using a distance-based design-focused optimization model
Özdemir, Akın; Şahin, 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°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.
AtıfScopus9WoS9OpenAlex8İncele - MakaleYalnız künye2019Scopus SJRQ3Production of enantiomerically enriched chiral carbinols using Weissella paramesenteroides as a novel whole cell biocatalyst
Tozlu, Caner; Şahin, Engin; Serencam, Hüseyin; Dertli, Enes
In this study, four bacterial strains were tested for their ability to reduce acetophenones to its corresponding alcohol. Among these strains Weissella paramesenteroides N7 was found to be the most successful biocatalyst to reduce the ketones to the corresponding alcohols. The reaction conditions were systematically optimized for W. paramesenteroides N7 that resulted in high enantioselectivity and conversion rates for the bioreduction. The scale-up asymmetric reduction of 1-(4-methoxyphenyl) propan-1-one (1r) by W. paramesenteroides N7 gave (R)-1-(4-methoxyphenyl) propan-1-ol (2r) with 94% yield and >99% enantiomeric excess. This is the first report showing the synthesis of (R)-1-(4-methoxyphenyl) propan-1-ol (2r) in enantiopure form using a biocatalyst on a gram scale. The whole cell catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that W. paramesenteroides N7 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest as a promising and alternative green approach.
AtıfScopus12WoS10OpenAlex11İncele - 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