Reduction Of Ketones Research Articles

Engineering ketoreductases for the enantioselective synthesis of chiral alcohols.

The use of engineered ketoreductases (KREDS), both as whole microbial cells and isolated enzymes, in the highly enantiospecific reduction of prochiral ketones is reviewed. The homochiral alcohol products are key intermediates in, for example, pharmaceuticals synthesis. The application of sophisticated protein engineering and enzyme immobilisation techniques to increase industrial viability are discussed.

Triflylpyridinium Promoted Controllable Reduction of Carboxylic Acids to Aldehydes

Triflylpyridinium Promoted Controllable Reduction of Carboxylic Acids to Aldehydes

A general synthesis of aromatic and heteroaromatic lipoxin B4 analogues.

Lipoxins are an important class of pro-resolving mediators that play a crucial role in the resolution of inflammation. Thus, the synthesis of more chemically and metabolically stable synthetic lipoxin analogues is an area of significant interest. Whereas synthetic analogues of lipoxin A4 (LXA4) have been well studied, analogues of lipoxin B4 (LXB4) have been the focus of considerably less attention. Herein we report the asymmetric synthesis of a focused library of LXB4 mimetics in which the triene core of the molecule has been replaced with different aromatic and heteroaromatic rings. The synthesis of each of these analogues was achieved by a general strategy in which the key steps were a Suzuki cross coupling between a common upper chain fragment and an aromatic lower chain, followed by a stereoselective ketone reduction.

Expeditious access to cis-β-aryl, γ-alkyl disubstituted (±)-γ-butyrolactones via nickel-hydride catalysis.

The 1,4-reduction of β- and γ-substituted butenolides using 5 mol% of NiCl2·6H2O and NaBH4 in MeOH for rapid access to cis-β,γ-disubstituted γ-butyrolactones is described. The reaction was selective for cis-products, which were obtained in good to excellent yields. This study showcased the influence of steric hindrance and angle strain on the diastereoselectivity outcome of conjugate reductions facilitated by in situ generated nickel-hydride.

Organic Acid to Nitrile: A Chemoenzymatic Three-Step Route.

Various widely applied compounds contain cyano-groups, and this functional group serves as a chemical handle for a whole range of different reactions. We report a cyanide free chemoenzymatic cascade for nitrile synthesis. The reaction pathway starts with a reduction of carboxylic acid to aldehyde by carboxylate reductase enzymes (CARs) applied as living cell biocatalysts. The second - chemical - step includes in situ oxime formation with hydroxylamine. The final direct step from oxime to nitrile is catalyzed by aldoxime dehydratases (Oxds). With compatible combinations of a CAR and an Oxd, applied in one-pot two-step reactions, several aliphatic and aryl-aliphatic target nitriles were obtained in more than 80% conversion. Phenylacetonitrile, for example, was prepared in 78% isolated yield. This chemoenzymatic route does not require cyanide salts, toxic metals, or undesired oxidants in contrast to entirely chemical procedures.

Synthesis of Selenoesters via Aldol Condensation and/or Conjugate Reduction and Their Antiviral Activities.

A variety of unsaturated selenoesters (including phenolic ones) were produced in good to high yields and with high E/Z ratios using TiCl4-promoted aldol condensation between Se-phenyl selenoacetate and their respective aldehydes without aqueous workup. A representative phenolic unsaturated selenoester was applied to acylation of tyrosine methyl ester without protection of the phenolic hydroxy groups to furnish the corresponding amino acid conjugate. The conjugate reduction of the unsaturated selenoesters including phenolic ones and selenocoumarin with HSiEt3 was catalyzed by B(C6F5)3 to afford the corresponding saturated selenoesters in good to high yields. This method was also applicable to the reduction of a saturated selenoester to the corresponding O-silyl hemiselenoacetal in a high yield. Moreover, most acyclic unsaturated selenoesters were found to show good multiple antiviral activities against HIV-1, HBV, and SARS-CoV-2.

Unusual aldehyde reductase activity for the production of full-length fatty alcohol by cyanobacterial aldehyde deformylating oxygenase

Aldehyde-deformylating oxygenase (ADO) is a non-heme di-iron enzyme that catalyzes the deformylation of aldehydes to generate alkanes/alkenes. In this study, we report for the first time that under anaerobic or limited oxygen conditions, Prochlorococcus marinus (PmADO) can generate full-length fatty alcohols from fatty aldehydes without eliminating a carbon unit. In contrast to ADO's native activity, which requires electrons from the Fd/FNR electron transfer complex, ADO's aldehyde reduction activity requires only NAD(P)H. Our results demonstrated that the yield of alcohol products could be affected by oxygen concentration and the type of aldehyde. Under strictly anaerobic conditions, yields of octanol were up to 31%. Moreover, metal cofactors are not involved in the aldehyde reductase activity of PmADO because the yields of alcohols obtained from apoenzyme and holoenzyme treated with various metals were similar under anaerobic conditions. In addition, PmADO prefers medium-chain aldehydes, specifically octanal (kcat/Km around 15 × 10−3 μM−1min−1). The findings herein highlight a new activity of PmADO, which may be applied as a biocatalyst for the industrial synthesis of fatty alcohols.

Cobalt Nanoparticles Formed upon Reaction of Cp*Co(III) Metallacycles with Na[BHEt3] Show Catalytic Activity in the Hydrosilylation of Aryl Ketones, Aldehydes and Nitriles

AbstractThe reactivity of the 2‐phenylpyridine‐derived [Cp*CoI(phpy‐κC,N)] metallacycle towards Et3SiH and hydrides was evaluated. The treatment of the same Co(III) complex with Na[BHEt3] resulted in its decomposition into cobalt nanoparticles. The hydride‐promoted decomposition of the metallacycle involves the transient formation of an elusive hydrido‐cobalt(III) intermediate, the traces of which were detected by 1H NMR spectroscopy at sub‐ambient temperature. The Co nanoparticles produced from a 5 mol% and 10 mol% load of cobaltacycle and Na[BHEt3] respectively contain Co(0) that is responsible for the hydrosilylation by Et3SiH of arylketones into silylalkyl ethers. To minimize the residual side reduction of carbonyls by Na[BHEt3], a mixture of 5 mol% of the latter with 5 mol% of BEt3 was found to produce optimal hydrosilylation yields at 40 °C in 2 h. Under similar conditions, several arylnitriles were mono‐hydrosilylated into N‐silyl‐imines in yields ranging from 68 to 100 %.

Influence of metal oxide catalyst on co-pyrolysis of biomass and COVID-19 waste

ABSTRACT The disposal of waste generated by the COVID-19 pandemic is still a challenge to the government in most countries. The present study shines its light on the catalytic effect of metal oxide on converting COVID-19 waste i.e. used face masks into valuable products through co-pyrolysis. The co-pyrolysis trial was carried out for a mixture of waste face mask (WFM) and Moringa oleifera (MO) biomass at a constant temperature of 450°C for 15 min of resident time. This investigation focuses on studying the catalytic effect of calcium oxide (CaO) on the by-products of the pyrolysis process. From the FT-IR studies, it is observed that the CaO catalyst assisted to reduce oxygen as well as sulphur and carboxylic acids in the bio-oil due to its strong basic nature. The FE-SEM images suggest the increase in porous structure with catalytic pyrolysis (CP) char compared to non-catalytic pyrolysis (NCP) char. The catalytic activity of CaO increased the alcoholic content with a reduction in aldehydes and ketones in the bio-oil. The addition of WFM to the biomass with CaO catalyst pyrolysis (CP) delivered a higher oil yield of 52% compared to non-catalytic pyrolysis (NCP).

Recycling of Cofactors in Crude Enzyme Hydrogels as Co-immobilized Heterogeneous Biocatalysts for Continuous-Flow Asymmetric Reduction of Ketones.

Flow biocatalysis involving oxidoreductase is limited by the difficulty in recycling expensive cofactors. In this study, an enzyme-rich hydrogel monolithic microreactor was developed via in situ microfluidic assembly of inexpensive crude enzymes. This porous gel biocatalyst exhibited good tethering functions to nicotinamide cofactors; thus, they were retained by the hydrogel to controllably form a novel heterogeneous biocatalyst with self-sufficient cofactors. The flow asymmetric production of a chiral alcohol in this cofactor-entrapped gel microreactor achieved >99 % enantioselectivity and a high space-time yield of 46.3 g L-1 h-1 at 94.8 % conversion. Moreover, the turnover number of cofactors reached as high as 4800 after continuous operation of 160 reactor volumes, realizing significantly higher utilization of the cofactors compared with many reported strategies. Furthermore, this engineered heterogeneous biocatalyst exhibited improved performance in terms of product tolerance and storage stability, paving the way for a green, cost-effective, and sustainable continuous-flow production of enantiopure alcohols.

Triflylpyridinium Enables Rapid and Scalable Controlled Reduction of Carboxylic Acids to Aldehydes using Pinacolborane.

Building up new and efficient methods for the controlled conversion of carboxylic acids to aldehydes is important. Herein, we report a rapid, modular and scalable method for the conversion of carboxylic acids to aldehydes using pinacolborane at ambient temperature, in which a triflylpyridinium reagent is used. The conversion of carboxylic acid to intermediate acylpyridinium by triflylpyridinium is new. A binary pyridine-coordinated boronium complex is generated after reduction. The unprecedented reduction of the acylpyridinium by HBpin opens up a practically direct synthesis of aldehydes from carboxylic acids. Theoretical studies indicate that the reduction of acylpyridinium requires a lower activation free energy than that of the product aldehyde. The synthetic advantage of this protocol is further highlighted by the scalable synthesis of aldehyde via continuous flow process. Configuration retention for chiral acids are presented in those syntheses.

Triflylpyridinium Enables Rapid and Scalable Controlled Reduction of Carboxylic Acids to Aldehydes using Pinacolborane

AbstractBuilding up new and efficient methods for the controlled conversion of carboxylic acids to aldehydes is important. Herein, we report a rapid, modular and scalable method for the conversion of carboxylic acids to aldehydes using pinacolborane at ambient temperature, in which a triflylpyridinium reagent is used. The conversion of carboxylic acid to intermediate acylpyridinium by triflylpyridinium is new. A binary pyridine‐coordinated boronium complex is generated after reduction. The unprecedented reduction of the acylpyridinium by HBpin opens up a practically direct synthesis of aldehydes from carboxylic acids. Theoretical studies indicate that the reduction of acylpyridinium requires a lower activation free energy than that of the product aldehyde. The synthetic advantage of this protocol is further highlighted by the scalable synthesis of aldehyde via continuous flow process. Configuration retention for chiral acids are presented in those syntheses.

Structure of the Reductase Domain of a Fungal Carboxylic Acid Reductase and Its Substrate Scope in Thioester and Aldehyde Reduction.

The synthesis of aldehydes from carboxylic acids has long been a challenge in chemistry. In contrast to the harsh chemically driven reduction, enzymes such as carboxylic acid reductases (CARs) are considered appealing biocatalysts for aldehyde production. Although structures of single- and didomains of microbial CARs have been reported, to date no full-length protein structure has been elucidated. In this study, we aimed to obtain structural and functional information regarding the reductase (R) domain of a CAR from the fungus Neurospora crassa (Nc). The NcCAR R-domain revealed activity for N-acetylcysteamine thioester (S-(2-acetamidoethyl) benzothioate), which mimics the phosphopantetheinylacyl-intermediate and can be anticipated as the minimal substrate for thioester reduction by CARs. The determined crystal structure of the NcCAR R-domain reveals a tunnel that putatively harbors the phosphopantetheinylacyl-intermediate, which is in good agreement with docking experiments performed with the minimal substrate. In vitro studies were performed with this highly purified R-domain and NADPH, demonstrating carbonyl reduction activity. The R-domain was able to accept not only a simple aromatic ketone but also benzaldehyde and octanal, which are typically considered to be the final product of carboxylic acid reduction by CAR. Also, the full-length NcCAR reduced aldehydes to primary alcohols. In conclusion, aldehyde overreduction can no longer be attributed exclusively to the host background.

Response surface optimization of product yields and biofuel quality during fast hydrothermal liquefaction of a highly CO2-tolerant microalgae

The effects of biochemical components and processing variables (e.g., temperatures, solid-liquid ratio, ethanol concentration, and time) during fast hydrothermal liquefaction of a highly CO2-tolerant microalgae (Micractinium sp.) on the product yields and biofuel quality were explored using response surface methodology coupled with central composite design. Results showed that the maximum bio-oil yield (51.4 %) was obtained at 321 °C for 49 min at ethanol concentration of 75 % and solid-liquid ratio of 15.3 %. Among different studied parameters, ethanol concentration showed the highest significant impact on the bio-oil yield due to the low P-value and high F-value in ANOVA analysis. Furthermore, the chemical compositions of bio-oils were determined, which showed that the increase of ethanol concentration in the solvent not only increased the bio-oil yield but also promoted the bio-oil quality by reduction of carboxylic acids and nitrogen-containing compounds with simultaneous enhancement of esters in the bio-oil. The present results show that fast hydrothermal liquefaction is a promising approach to convert the microalgae into high quality biofuels rich in esters.

Effects of Starter Cultures and Type of Casings on the Microbial Features and Volatile Profile of Fermented Sausages

In the literature, the effect of the type of casing on fermented sausages is quite unexplored, while several studies are focused on the impact of starter cultures. Therefore, this paper studied the effect of three commercial starter cultures and two casings (natural or collagen) on Italian fermented sausages. Physico-chemical parameters (aw, pH, weight loss), microbiota, aroma profile and sensory analysis were evaluated. Results showed that collagen casings promoted a higher reduction of pH and weight loss. Concerning the microbiota, samples with natural casing had higher counts of lactic acid bacteria, while yeast proliferation was promoted in those with collagen. Regardless of the starters and casings applied, levels of enterococci and Enterobacteriaceae were low (≤2 log CFU/g). The aroma profile was significantly affected by casing: despite the starter applied, the presence of collagen casing favoured acid accumulation (mainly acetate and butanoate) and reduction of ketones. Sensory analysis highlighted significant differences only for odour, colour intensity and sourness. The differences observed suggest that collagen casings may provide a greater availability of oxygen. Overall, casings rather than starter cultures impact the microbial and sensorial features of fermented sausages.

A Safer Reduction of Carboxylic Acids with Titanium Catalysis.

Ammonia-borane, shown previously to react with carboxylic acids under reflux to form primary amides, reduces acids to alcohols at room temperature in the presence of catalytic TiCl4. The process, which is tolerant of a variety of potentially reactive functional groups, including N-protected amino acids, can be employed for the selective reduction of acids in the presence of amides, nitriles and, to some extent, esters. Aliphatic acids can be selectively reduced in the presence of aromatic acids.

A triphos-modified tungsten piano-stool complex for the homogeneous (conjugate) hydrogenation of ketones and esters

We disclose the synthesis, characterization, and catalytic application of a triphos-tagged, non-pincer-type tungsten complex. The pertinent W-based half-sandwich compound was used in the homogeneous hydrogenation of ketones and esters to afford the corresponding alcohols. Furthermore, the introduced base metal catalyst facilitated the conjugate reduction of enoates to yield the respective CC-bond-free esters. Most of the applied substrate ketones were convertible under very mild reaction conditions (room temperature, 5 bar H2) in the presence of t–BuONa. The exchange of the cation in the auxiliary base from Na+ to Li+ turned out to be crucial for the successful reduction of the carbonyl ester group. The deployed organometallic complex is readily weighable and can be handled on the laboratory bench outside a sealed glove box system.

Metabolism Profile of Mequindox in Sea Cucumbers In Vivo Using LC-HRMS.

In this work, the metabolism behavior of mequindox (MEQ) in sea cucumber in vivo was investigated using LC-HRMS. In total, nine metabolites were detected and identified as well as the precursor in sea cucumber tissues. The metabolic pathways of MEQ in sea cucumber mainly include hydrogenation reduction, deoxidation, carboxylation, deacetylation, and combinations thereof. The most predominant metabolites of MEQ in sea cucumber are 2-iso-BDMEQ and 2-iso-1-DMEQ, with deoxidation and carbonyl reduction as major metabolic pathways. In particular, this work first reported 3-methyl-2-quinoxalinecarboxylic acid (MQCA) as a metabolite of MEQ, and carboxylation is a major metabolic pathway of MEQ in sea cucumber. This work revealed that the metabolism of MEQ in marine animals is different from that in land animals. The metabolism results in this work could facilitate the accurate risk assessment of MEQ in sea cucumber and related marine foods.

Study on the aroma formation of baked sea bass (Lateolabrax japonicus) via solvent-assisted flavor evaporation coupled with gas chromatography-mass spectrometry (SAFE-GC-MS) analysis

The study aims to reveal the formation pathways of main aroma volatile compounds of sea bass during baking processing. Total of 3 heat treatments were used in this study to explore the effects of different conditions on flavor performance. The difference between 3 treatments depended on oxygen engagement and sealed/unsealed environments. The results showed that all the heating treatments promoted the scores of roasted meaty, fatty, and sweet notes in sea bass samples. Those 3 aroma profiles contributed to the increase acceptability. On the contrary, the fishy and grassy notes leaded the decrease scores of acceptability. The correlation was mainly due to changes in concentration of key aroma compounds. Among the treatments, anaerobic sealed heating treatment promoted the isomerization of the olefins; reduction of aldehydes; and electrocyclic reaction. Aerobic sealed heating treatment responded for the oxidation of the aldehydes, and deformation-oxygenation reactions. Aerobic unsealed heating treatment promoted the reaction of degradation of fatty acids and conversion of the unsaturated aldehydes. Then, unsealed environment leaded to the loss of large amounts of aroma compounds. Our findings will provide scientific information on regulating flavor formation of sea bass during baking through controlling processing conditions.

Efficient MPV reductions of biomass-derived aldehydes and ketones over an assembling zirconium-gallic acid hybrid under mild condition

The utilization of natural renewable resources for the synthesis of catalytic materials and their application for the sustainable production of high value chemicals from lignocellulose is a very attractive topic. Herein, F127 was used as a dispersant to promote the formation of robust organic–inorganic hybrids (Zr5-GAF) of gallic acid (GA) selected as organic ligands with Zr in ethanol for the Meerwein-Ponndorf-Verley reduction of biomass-derived aldehydes and ketones. Multiple characterizations proved that F127 enhanced the connectivity of Zr and GA while effectively increased the specific surface area and pore volume of the catalyst. The addition of F127 shifted the binding energy of Zr and O to higher values and thus obtained more and stronger Lewis acid-base sites. The synthesized Zr5-GAF helped to yield near-quantitative furfuryl alcohol (FA, 94.7%) and a much higher FA production rate than previously reported under mild conditions (100 ℃, 1 h). Moreover, kinetic experiments showed that the reduction activation energy of furfural was as low as 36.04 kJ/mol and Zr5-GAF exhibited good recyclability for at least six reaction cycles. The approach of designing heterogeneous catalytic materials from GA with economical, environmentally friendly and sustainable characteristics has great potential in green chemistry.