Reduction Of Acetophenone Research Articles

Supramolecular chiral electrochemical reduction of acetophenone with hybridization of a chiral multifarene and Au nanoparticles

A supramolecular chiral electrode was constructed by layer-by-layer assembly of gold nanoparticles (AuNPs) and an S-chiral multifarene [3,2,1] (S-CMF) on the surface of a glassy carbon electrode, which was applied for the electroreduction of acetophenone. The host-guest encapsulation of the substrate within the chiral cavity was confirmed by 1H NMR, fluorescence titration, and molecular simulation. The composite on the electrode surface was characterized by electrochemical impedance spectroscopy (EIS) and transmission electron microscopy (TEM). Optimization of the electrolysis process was performed to give a high yield of 70.9% and high enantioselectivity of 63.9% ee, which exhibited superior reactivity to the previously reported materials. The repeatability of the experiment was tested via five separate experiments and indicated consistent stability, recyclability, and reusability of the novel chiral electrode. The proposed mechanism involved supramolecular encapsulation, two single-electron transfer steps, and proton addition. The chiral electroorganic reduction was extended to more substrates to provide successful yields and enantioselectivity.

Efficient biosynthesis of (S)-1-[2-(trifluoromethyl)phenyl]ethanol by a novel isolate Geotrichum silvicola ZJPH1811 in deep eutectic solvent/cyclodextrin-containing system

This study aimed to develop a biotransformation process for the production of (S)-1-[2-(trifluoromethyl)phenyl]ethanol, a key chiral intermediate of Plk1 inhibitor, and increase its productivity through medium engineering strategy. A fungus isolate Geotrichum silvicola ZJPH1811 was adopted as biocatalyst for 2ʹ-(trifluoromethyl)acetophenone reduction, and gave the best performance with > 99.2% product ee. To improve the yield, choline acetate/cysteine (ChAc/Cys) was introduced as co-solvent in reaction system, which accelerated mass transfer and protected cells from substrate inhibition. Moreover, a synergistic effect of methylated-β-cyclodextrin (MCD) and ChAc/Cys was found in the bioreduction, with further enhancement in substrate concentration and cell membrane permeability. Compared with buffer system, in the developed ChAc/Cys-MCD-containing system, substrate loading and product yield were increased by 6.7-fold and 2.4-fold respectively. This is the first report on (S)-1-[2-(trifluoromethyl)phenyl]ethanol production with G. silvicola, and provides valuable insight into the synergistic effect of DES and CDs in biocatalysis.

Synthesis of new mixed (-)-menthylalkyltin dihydrides. stereoselective reduction of chiral and prochiral ketones

This paper reports de synthesis of a series of (-)-menthylalkyltin dihydrides, (-)-MenRSnH2 (R = Me, n-Bu, i-Pr, t-Bu, Neophyl), starting from (-)-menthyltrimethyltin. The new (-)-menthylalkyltin dihydrides 12–16 were used in a study on the stereoselective reduction of chiral (-)-menthone under different reaction conditions. Also the results obtained in the reductions of prochiral acetophenone (27) and 2-acetylnaphthalene (28), with (-)-menthylmethyl- (12) and (-)-menthyli-propyltin (14) dihydrides are informed. Some physical properties as well as full 1H-, 13C-, and 119Sn NMR data of the new organotin compounds are informed.

Promotion of the Asymmetric Reduction of Prochiral Ketone with Recombinant E. coli Through Strengthening Intracellular NADPH Supply by Modifying EMP and Introducing NAD Kinase

The intracellular NADPH insufficient supply is the main bottleneck to the synthesis of chiral alcohols by asymmetric reduction with whole-cell catalysis. Herein, we provide a novel strategy to strengthen intracellular NADPH supply through introducing an NADP+-dependent glyceraldehyde 3-phosphate dehydrogenase (gapB from Bacillus subtilis 168) into the Embden-Meyerhof pathway and a NAD kinase (yfjB from E. coli MG1655) to further enhance the NADP(H) pool. A recombinant E. coli (E. coli BL21 (DE3)/pETDuet-1-gapB-yueD&pET28a-yfjB) was constructed to co-express gapB and yfjB with a carbonyl reductase gene yueD together. The result showed that the intracellular NADPH amount increased by 134.4% with the strategy. To the model reaction (asymmetric reduction of acetophenone to S-phenyl ethanol), the yield was 3.7-fold with this strategy compared to the control. This provides a technological route for strengthening the intracellular NADPH supply in E. coli for biocatalysis and biosynthesis.

Structure Sensitivity of Acetophenone Reduction on Palladium-Modified Platinum Single-Crystal Electrodes

The electrochemical reduction of acetophenone has been investigated in acidic conditions on the three low-index [namely (111), (110), and (100)] single-crystal platinum electrodes coated with an at...

Heterogeneous Catalysts “on the Move”: Flow Chemistry with Fluid Immobilised (Bio)Catalysts

As both, continuous synthesis and (bio‐)catalysis gained increasing interest in research as well as for industrial applications, ways for merging these fields enables novel opportunities for modern sustainable process development. In this contribution, an alternative approach for the application of immobilized enzymes in continuous flow processes is presented utilizing heterogeneous biocatalysts as a mobile phase. Based on superabsorber‐entrapped enzymes and whole cells as a “fluid heterogeneous phase”, a segmented hydrogel/organic solvent system was developed. Its applicability was investigated with two entirely different model reaction systems, namely the alcohol dehydrogenase (ADH)‐catalysed reduction of acetophenone, and the aldoxime dehydratase (Oxd)‐catalysed dehydration of octanal oxime. In particular for solvent labile catalytic systems, this approach offers an alternative for the application of immobilized biocatalysts in a continuously running process beyond the “classic” packed bed and wall coated reactors.

Taguchi analysis and asymmetric keto-reduction of acetophenone and its derivatives by soil filamentous fungal isolate: Penicillium rubens VIT SS1

Microbial asymmetric reduction of ketone is an efficient tool for the synthesis of chiral alcohols. This research focuses on exploring the soil fungal isolates for their ability toward the keto reduction of acetophenone and its derivatives to their corresponding chiral alcohols using growing cells. Bioreduction of acetophenone, 4-fluoro acetophenone, 4-methyl acetophenone, and 3-hydroxy acetophenone was carried out using different fungal cultures isolated from soil. Among the fungal isolates, Penicillium sp. and Aspergillus sp. showed significant bioconversion with varying enantio-selectivity. However, the Penicillium sp. has shown the maximum ability of bioreduction. The potential isolate was characterized using the internal transcribed spacer (ITS) region and found to be Penicillium rubens VIT SS1 (Genbank accession number: MK063869.1), which showed higher conversion and selectivity > 90%. The biocatalyst production and the reaction conditions were optimized using Taguchi analysis. The process conditions such as pH, temperature, media components, cosolvent, and substrate dosing were evaluated for the bioreduction of 3-hydroxy acetophenone, which is a key chiral intermediate of Phenylephrine and Rivastigmine using P. rubens VIT SS1. This study concludes about the potential of fungal cultures for sustainable synthesis of key chiral intermediates of Phenylephrine and Rivastigmine, similarly many aromatic chiral alcohols in simpler, novel, and cost-effective manner.

Corrigendum: Highly Enantioselective Production of Chiral Secondary Alcohols with Candida zeylanoides as a New Whole Cell Biocatalyst.

The increasing demand for biocatalysts in synthesizing enantiomerically pure chiral alcohols results from the outstanding characteristics of biocatalysts in reaction, economic, and ecological issues. Herein, fifteen yeast strains belonging to three food originated yeast species Candida zeylanoides, Pichia fermentans, and Saccharomyces uvarum were tested for their capability for asymmetric reduction of acetophenone to 1-phenylethanol as biocatalysts. Of these strains, C. zeylanoides P1 showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high yields. The preparative scale asymmetric bioreduction of 4-nitroacetophenone (1m) by C. zeylanoides P1 gave (S)-1-(4-nitrophenyl)ethanol (2m) with 89% yield and > 99% enantiomeric excess. Compound 2m has been obtained in an enantiomerically pure and inexpensive form. Additionally, these results indicate that C. zeylanoides P1 is a promising biocatalyst for the synthesis of chiral alcohols in industry.

Modelling Photosynthesis with ZnII -Protoporphyrin All-DNA G-Quadruplex/Aptamer Scaffolds.

All-DNA scaffolds act as templates for the organization of photosystem I model systems. A series of DNA templates composed of ZnII -protoporphyrin IX (ZnII PPIX)-functionalized G-quadruplex conjugated to the 3'- or 5'-end of the tyrosinamide (TA) aptamer and ZnII PPIX/G-quadruplex linked to the 3'- and 5'-ends of the TA aptamer through a four-thymidine bridge. Effective photoinduced electron transfer (ET) from ZnII PPIX/G-quadruplex to bipyridinium-functionalized tyrosinamide, TA-MV2+ , bound to the TA aptamer units is demonstrated. The effectiveness of the primary ET quenching of ZnII PPIX/G-quadruplex by TA-MV2+ controls the efficiency of the generation of TA-MV+. . The photosystem-controlled formation of TA-MV+. by the different photosystems dictates the secondary activation of the ET cascade corresponding to the ferredoxin-NADP+ reductase (FNR)-catalysed reduction of NADP+ to NADPH by TA-MV+. , and the sequestered alcohol dehydrogenase catalysed reduction of acetophenone to 1-phenylethanol by NADPH.

Modelling Photosynthesis with ZnII‐Protoporphyrin All‐DNA G‐Quadruplex/Aptamer Scaffolds

AbstractAll‐DNA scaffolds act as templates for the organization of photosystem I model systems. A series of DNA templates composed of ZnII‐protoporphyrin IX (ZnIIPPIX)‐functionalized G‐quadruplex conjugated to the 3′‐ or 5′‐end of the tyrosinamide (TA) aptamer and ZnIIPPIX/G‐quadruplex linked to the 3′‐ and 5′‐ends of the TA aptamer through a four‐thymidine bridge. Effective photoinduced electron transfer (ET) from ZnIIPPIX/G‐quadruplex to bipyridinium‐functionalized tyrosinamide, TA‐MV2+, bound to the TA aptamer units is demonstrated. The effectiveness of the primary ET quenching of ZnIIPPIX/G‐quadruplex by TA‐MV2+ controls the efficiency of the generation of TA‐MV+.. The photosystem‐controlled formation of TA‐MV+. by the different photosystems dictates the secondary activation of the ET cascade corresponding to the ferredoxin‐NADP+ reductase (FNR)‐catalysed reduction of NADP+ to NADPH by TA‐MV+., and the sequestered alcohol dehydrogenase catalysed reduction of acetophenone to 1‐phenylethanol by NADPH.

New alkoxymethyl-functionalized pyridinium-based chiral ionic liquids: synthesis, characterization and properties

An efficient solvent-free synthesis of a new family of functionalized chiral ionic liquids based on pyridinium cation has been developed from low-cost chiral terpenoid alcohols. An exhaustive characterization was performed using state-of-the-art techniques, such as ESI–MS, ATR FT-IR and NMR (1H, 13C, 11B, 31P, 19F) spectroscopy. Thermal properties of this new class of chiral ionic liquids were studied by TGA and DSC analyses. Catalytic potential of the synthesized CILS was also evaluated in the asymmetric reduction of prochiral acetophenones.

Enzyme immobilization on porous chitosan hydrogel capsules formed by anionic surfactant gelation.

Sodium dodecyl sulfate (SDS)-chitosan hydrogels have been employed for adsorption of anionic dyes and metallic substances. Two mutant forms of Thermoanaerobacter ethanolicus alcohol dehydrogenase (TeSADH) were used as model enzymes to develop a novel enzyme immobilization technique employing newly formulated porous chitosan hydrogels. The enzyme immobilized on chitosan hydrogel capsules formed by 5g/l SDS gelation and subsequent treatment with 0.05M NaOH was 28-35% higher in NADPH production than that formed by 20g/l SDS gelation only under the same conditions. A 48-h asymmetric biphasic reduction of acetophenone with immobilized TeSADH enzyme at 50 °C showed 68% increase in (R)-1-phenylethanol production than the free enzyme. Compared to the free enzyme which denatured and lost its activity at 80 °C, the immobilized enzyme retained about 25% of its initial activity after 2-h incubation. In contrast to the conventional chitosan hydrogel which suffers thermal and operational stability, the newly formulated porous chitosan hydrogel capsules have excellent enzyme loading efficiency and stable at harsh temperatures. Especially, this newly developed enzyme immobilization method would be applicable for food processing.

Characterization and Application of a Robust Glucose Dehydrogenase from Paenibacillus pini for Cofactor Regeneration in Biocatalysis.

Glucose dehydrogenases are important auxiliary enzymes in biocatalysis, employed in the regeneration of reduced nicotinamide cofactors for oxidoreductase catalysed reactions. Here we report the identification and characterization of a novel glucose-1-dehydrogenase (GDH) from Paenibacillus pini that prefers NAD+ as cofactor over NADP+. The purified recombinant P. pini GDH displayed a specific activity of 247.5U/mg. The enzyme was stable in the pH range 4-8.5 and exhibited excellent thermostability till 50°C for 24h, even in the absence of NaCl or glycerol. Paenibacillus pini GDH was also tolerant to organic solvents, demonstrating its potential for recycling cofactors for biotransformation. The potential application of the enzyme was evaluated by coupling with a NAD+-dependent alcohol dehydrogenase for the reduction of acetophenone and ethyl-4-chloro-3-oxo-butanoate. Conversions higher than 95% were achieved within 2h with low enzyme loading using lyophilized cell lysate, suggesting that P. pini GDH could be highly effective for recycling NADH in redox biocatalysis.

Flow Process for Ketone Reduction Using a Superabsorber-Immobilized Alcohol Dehydrogenase from Lactobacillus brevis in a Packed-Bed Reactor.

Flow processes and enzyme immobilization have gained much attention over the past few years in the field of biocatalytic process design. Downstream processes and enzyme stability can be immensely simplified and improved. In this work, we report the utilization of polymer network-entrapped enzymes and their applicability in flow processes. We focused on the superabsorber-based immobilization of an alcohol dehydrogenase (ADH) from Lactobacillus brevis and its application for a reduction of acetophenone. The applicability of this immobilization technique for a biotransformation running in a packed bed reactor was then demonstrated. Towards this end, the immobilized system was intensively studied, first in a batch mode, leading to >90% conversion within 24 h under optimized conditions. A subsequent transfer of this method into a flow process was conducted, resulting in very high initial conversions of up to 67% in such a continuously running process.

Preparation of chiral alcohols by enantioselective reduction of prochiral ketones with Sinapis alba seeds as biocatalyst

The objective of this work is to apply yellow mustard seeds in the enzymatic reduction (biocatalysis) of acetophenone and its derivatives, providing a new biocatalyst for this type of reduction. The reaction parameters were optimized from acetophenone, resulting in 1-phenylethanol, with 68.5% conversion yield and 53% enantiomeric excess (e.e.), analyzed by GC and HPLC, respectively. Reactions to acetophenone and its derivatives were conducted in aqueous medium using buffers pH 6.0 and pH 6.5 in the presence of PVP. A polymer that can act as a protector preventing oxidation of peroxidase enzymes. The results for the derivatives presented low yields (4–18%: substances 5, 7 and 8), moderate (28–40%: substances 3, 4 and 6) and optimum (81%: substance 2) yields, with enantiomeric excesses varying from good to excellent results. Meta-substituted derivatives showed inversion of configuration in the presence of PVP. The biocatalyst was also tested in reactions with other carbonyl compounds, presenting moderate results. In this way, this work offers a new perspective of the application of PVP in biocatalysis reactions and a new biocatalyst for future applications.

Optimization of the transfer hydrogenation reaction of acetophenone on Ni@MOF-5 nanoparticles using response surface methodology

In this study, the transfer hydrogenation reduction of acetophenone using supported nickel on MOF as catalyst was investigated. BBD and RSM were employed to investigate the effect of the experimental parameters such as Ni content, catalyst content, temperature, and reaction time. Optimum reaction conditions for the formation of 1-phenylethanol were 45% mol of Ni content, 0.11 g of catalyst, reaction temperature at 83 °C, and reaction time 90 min. The catalyst was characterized by FESEM, EDX, FT-IR, XRD, and H2-TPR techniques. The catalyst-free reaction phase was analyzed by AAS, and fortunately, no leaching of nickel was detected.

Stereoselective Reducing Complexes Supported in Solid Phase: Preparation and Reactivity Study

AbstractTwelve new chiral chelating resins have been prepared using solid phase organic synthesis with the Merrifield and Wang resins and the bidentate amine 1,2‐ethylenediamine, followed by the coupling of asymmetric ketones such as 1‐phenyletanone, 4‐methyl‐2‐pentanone 4‐nitroacetophenone and 4‐methoxyacetophenone to form prochiral imines. The enantioselective reduction with borane and (R)‐(+)‐2‐Methyl‐CBS‐oxazaborolidine leads to the chiral resins with yields greater than 86%. We used these chiral resins to prepare 24 reducing complexes with alkali tetrahydroborates in a very simple way giving yields greater than 87%. Finally, we achieved a preliminary enantioselective reduction of acetophenone employing the Merrifield's chiral chelating resins obtaining the corresponding S alcohol in a 70:30 ratio with the R analog alcohol.

An Alkali-tolerant Carbonyl Reductase from Bacillus subtilis by Gene Mining: Identification and Application

Enantiopure alcohols have received much attention due to their widespread use as pharmaceutical intermediates. In the asymmetric biosynthesis of enantiopure alcohols, the excellent performance of carbonyl reductase makes it be the best choice as the biocatalysts. In this work, an alkali-tolerant carbonyl reductase (BsCR, encoded by yueD) from Bacillus subtilis (strain 168) was obtained through gene mining, and successfully heterologously expressed in Escherichia coli with pET-32a. BsCR showed excellent alkali resistance and even can keep more than 70% of its peak activity after incubation in Tris–HCl buffer at pH 9.0 for 40 h. The Michaelis constants and maximal velocity of the BsCR to NADPH (A) and ethyl 4-chloroacetoacetate (B) are $$K_{m}^{A}$$ = 5.390 × 10−2 mmol/L, $$K_{m}^{B}$$ = 1.855 mmol/L, and $$V_{max}$$ = 147.3 μmol·min−1·mg−1, respectively. Applying the E. coli BL21(DE3)/pET-32a-yueD to catalyze asymmetric reduction of ethyl 4-chloroacetoacetate and acetophenone, the yield of S-CHBE reached 89.9% and S-1-phenyl ethanol reached 66.7%, and e.e. of both products reached more than 99%. This work provides a novel CR for asymmetric reduction. A carbonyl reductase (BsCR) and its gene were identified through gene mining, and overexpressed in Escherichia coli BL21(DE3) for whole-cell biocatalytic asymmetric reduction

Response surface methodology as optimization strategy for asymmetric bioreduction of acetophenone using whole cell of Lactobacillus senmaizukei

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.

Micrometer-Sized Water Droplets Induce Spontaneous Reduction.

Bulk water serves as an inert solvent for many chemical and biological reactions. Here, we report a striking exception. We observe that in micrometer-sized water droplets (microdroplets), spontaneous reduction of several organic molecules occurs, pyruvate to lactate, lipoic acid to dihydrolipoic acid, fumarate to succinate, and oxaloacetate to malate. This reduction proceeds in microdroplets without any added electron donors or acceptors and without any applied voltage. In three of the four cases, the reduction efficiency is 90% or greater when the concentration of the dissolved organic species is less than 0.1 μM. None of these reactions occurs spontaneously in bulk water. One example demonstrating the possible broad application of reduction in water microdroplets to organic molecules is the reduction of acetophenone to form 1-phenylethanol. Taken together, these results show that microdroplets provide a new foundation for green chemistry by rendering water molecules to be highly electrochemically active without any added reducing agent or applied potential. In this manner, aqueous microdroplets might have provided a route for abiotic reduction reactions in the prebiotic era, thereby providing organic molecules with a reducing power before the advent of biotic reducing machineries.