Ketone Products Research Articles

Synergistic photobiocatalysis for enantioselective triple radical sorting.

Multicomponent reactions - those where three or more substrates combine into a product - have been highly useful in rapidly building chemical building blocks of increased complexity4, but achieving this enzymatically has remained rare.5 This limitation primarily arises because an enzyme's active site is not typically set up to address multiple substrates, especially in cases involving multiple radical intermediates6. Recently, chemical catalytic radical sorting has emerged as an enabling strategy for a variety of useful reactions7,8. However, making such processes enantioselective is highly challenging due to the inherent difficulty in the stereochemical control of radicals9. Here, we repurpose a thiamine-dependent enzyme10,11 through directed evolution, combine it with photoredox catalysis, to achieve a photobiocatalytic enantioselective three-component radical cross-coupling. This approach combines three readily available starting materials - aldehydes, α-bromo-carbonyls and alkenes - to give access to enantioenriched ketone products. Mechanistic investigations provide insights into how this dual photo-/enzyme system precisely directs the three distinct radicals involved in the transformation, unlocking new enzyme reactivity. Our approach has achieved exceptional stereoselectivity, with 25 out of 33 examples achieving ≥97% enantiomeric excess.

Effect of five lactic acid bacteria on the flavor quality of fermented sweet potato juice

The purpose of this research was to assess the impact of 5 lactic acid bacteria (LAB), Lactiplantibacillus plantarum, Lacticaseibacillus casei, Streptococcus thermophilus, Lacticaseibacillus rhamnosus and Lactobacillus delbrueckii subsp. bulgaricus on the characteristic flavor of the fermented sweet potato juice. Following the fermentation process, significant variations were observed in the concentrations of sugars, organic acids, as well as the overall volatile aroma compounds. LAB can effectively facilitate the production of volatile organic compounds (VOCs), including acids and ketones, thereby enhancing the aroma quality. Inoculation fermentation by LAB decreased the sweet and nutty odor, and increased fresh, floral, and citrus aroma of the sweet potato juice. The sweet potato juice fermented by 5 lactic acid bacteria strains had different flavor features, while the sample of Lp10 showed the highest overall acceptability. Compared to other strains, L. plantarum exerted a more significant influence on the volatile compounds present in fermented sweet potato juice.

Access to Ketones via Nickel-Catalyzed Coupling between S-2-Pyridyl Thioesters and Redox-Active Esters Using an Organic Reductant.

A nickel-catalyzed coupling between S-2-pyridyl thioesters and redox-active esters has been reported. Diludine was used as a reductant in this strategy. Our method rapidly achieves the target ketone products in moderate to good yield. The construction of nonanomeric C-acyl glycosides was realized through the approach as well.

Identification of Urinary Glucose and Urinary Ketones in Pulmonary Tuberculosis Patients Receiving Anti-Tuberculosis Drug Therapy (OAT) at the Tlogosari Wetan Health Center

Tuberculosis is a contagious infection caused by Mycobacterium tuberculosis. Anti-Tuberculosis Drug Therapy (OAT) given also has side effects, one of which is hepatotoxicity. Laboratory examination of urine glucose identification can show if there is damage to the kidney glomerulus in the filtration process. OAT such as isoniazid can affect the breakdown of fat and cause increased ketone production, especially in individuals who have low carbohydrate intake so that if the excess amount will be excreted through urine (ketonuria). The purpose of this study was to identify urine glucose and urinary ketones in non-DM pulmonary TB patients with OAT treatment at the Tlogosari Wetan Health Center based on treatment phase, gender, and age. This type of research is descriptive observational with a cross sectional approach. The study sample was a urine sample from a non-DM pulmonary TB patient. The examination method used is dyeing using a reagent strip test. The results of the study from a total of 30 non-DM pulmonary TB patients with OAT therapy (100%). A total of 6 (20%) patients identified urinary glucose, with details of intensive phase treatment 2 (7%) trace urine glucose patients (±), while in advanced phase 2 (7%) patients identified trace urine glucose (±) and 2 (7%) low urine glucose patients (+1). The majority of positive urine glucose results were experienced by men with vulnerable elderly age (46-65 years) as many as 4 patients (14%). The results of urine ketone identification showed that 2 (6.6%) patients were identified with urine ketones, namely trace (±) in the intensive phase treatment, while 15 patients in the advanced phase of urine ketones were all negative.The majority of positive urinary ketone results were experienced by vulnerable men of adult age (26-45 years) as much as 2 caseins (14%). Conclusion: Of the 30 non-DM pulmonary TB patients with OAT therapy who met the inclusion criteria, there were 6 (20%) patients identified with urinary glucose and 2 (6.6%) patients identified with urinary ketones. The impact of this study is expected to encourage non-DM pulmonary TB patients to take OAT and do regular medical check-ups.

Supramolecular Modulation for Selective Mechanochemical Iron‐Catalyzed Olefin Oxidation

AbstractThe development of a mechanochemical Fe‐catalyzed Wacker oxidation of olefins with a sustainable and benign procedure holds significant promise for industrial applications. However, navigating the intricate interactions inherent in ball‐milling conditions to fine‐tune reaction selectivity remains a formidable challenge. Herein, leveraging the dispersive and/or trapping properties of cyclodextrins, an innovative mechanochemical approach is developed through the integration of cyclodextrins into a Fe‐catalyzed system, enabling a streamlined Wacker oxidation process from simple and/or commercially available alkenes. Our efforts have yielded optimized mechanochemical conditions demonstrating exceptional reactivity and selectivity in generating a diverse array of ketone products, markedly enhancing catalytic efficiency compared to conventional batch methods. Mechanistic investigations have revealed a predominantly Markovnikov‐selective catalytic cycle, effectively minimizing undesired alcohol formation, hydrogenation, and the other competing pathways, boosting both reaction yield and selectivity.

Supramolecular Modulation for Selective Mechanochemical Iron-Catalyzed Olefin Oxidation.

The development of a mechanochemical Fe-catalyzed Wacker oxidation of olefins with a sustainable and benign procedure holds significant promise for industrial applications. However, navigating the intricate interactions inherent in ball-milling conditions to fine-tune reaction selectivity remains a formidable challenge. Herein, leveraging the dispersive and/or trapping properties of cyclodextrins, an innovative mechanochemical approach is developed through the integration of cyclodextrins into a Fe-catalyzed system, enabling a streamlined Wacker oxidation process from simple and/or commercially available alkenes. Our efforts have yielded optimized mechanochemical conditions demonstrating exceptional reactivity and selectivity in generating a diverse array of ketone products, markedly enhancing catalytic efficiency compared to conventional batch methods. Mechanistic investigations have revealed a predominantly Markovnikov-selective catalytic cycle, effectively minimizing undesired alcohol formation, hydrogenation, and the other competing pathways, boosting both reaction yield and selectivity.

A Polyoxotungstate Stabilized Copper Catalyst for Green and Efficient Transformation of Alcohols to Ketones

AbstractA water‐soluble copper catalyst (NH4)8[Cu2(H2O)8W12O42] ⋅ 4H2O is prepared by the generated paratunngstate B in situ, which can catalyze the H2O2 oxidation of cyclohexanol to cyclohexanone with a yield above 98 % in water under much milder conditions of 35 °C and atmospheric pressure, and the substrate can be extend to other secondary alcohols, potentially leading to an economical, green, and efficient ketone production method for industrial use.

Optimization of Biocatalytic Rhododendrol Production from Biogenic Rhododendrol Glycosides.

An enzyme-catalyzed synthesis of rhododendrol, an intermediate in the production of raspberry ketone, was investigated. The approach involves the enzymatic hydrolysis of rhododendrol glycosides into rhododendrol and a glycosidic residue. Rhododendrol glycosides, which are naturally derived from the inner bark of birch trees-a renewable resource-vary considerably in composition depending on the origin of the plants. In this study, mixtures of betuloside and apiosylrhododendrin from natural resources were used in different proportions. An in-depth study was conducted to assess the feasibility of the process. A mathematical model was developed based on studies of the kinetics and operational stability of the enzyme. The model for betuloside hydrolysis catalyzed by β-glucosidase was validated in batch, repetitive batch, and ultrafiltration membrane reactors. The highest productivity, ranging from 83.9 to 94.5 g L-1 day-1, was achieved in the latter. After screening nearly 50 enzymes, RAPIDASE emerged as a solution for the hydrolysis of apiosylrhododendrin, and the model was validated in a batch reactor. Model-based optimization enabled the prediction of input parameters for different compositions of biogenic rhododendrol glycosides to obtain consistent process output metrics.

Computational insight into the selectivity of [formula omitted]-valerolactone hydrodeoxygenation over Rh(111) and Ru(0001)

The observed difference in the selectivity towards alkane, ketone, and alcohol hydrodeoxygenation products over Ru and Rh catalysts is explored using a combination of density functional theory and microkinetics. Using γ-valerolactone as a model compound, we investigate the reaction mechanism in order to identify selectivity determining species. The effect of the coadsorbed water molecule as well as the higher adsorbate surface coverage on reaction barriers and energies is explored as well. The performed calculations suggest that the desired alkane product is formed from a ketone intermediate on Ru, and through both ketone and alcohol on Rh, although the selectivity towards alkane on Rh is much lower than on Ru.

Oxidative Catalytic Depolymerization of Lignin into Value-Added Monophenols by Carbon Nanotube-Supported Cu-Based Catalysts

Lignin valorisation into chemicals and fuels is of great importance in addressing energy challenges and advancing biorefining in a sustainable manner. In this study, on the basis of the high microwave absorption performance of carbon nanotubes (CNTs), a series of copper-oxide-loaded CNT catalysts (CuO/CNT) were developed to facilitate the oxidative depolymerization of lignin under microwave heating. This catalyst can promote the activation of hydrogen peroxide and air, effectively generating a range of reactive oxygen species (ROS). Through the application of electron paramagnetic resonance techniques, these ROS generated under different oxidation conditions were detected to elucidate the oxidation mechanism. The results demonstrate that the •OH and O2•− play a crucial role in the formation of aldehyde and ketone products through the cleavage of lignin Cβ-O and Cα-Cβ bonds. We further evaluated the catalytic performance of the CuO/CNT catalysts with three typical lignin feedstocks to determine their applicability for lignin biorefinery. The bio-enzymatic lignin produced a 13.9% monophenol yield at 200 °C for 20 min under microwave heating, which was higher than the 7% yield via hydrothermal heating conversion. The selectivity of G-/H-/S-type products was slightly affected, while lignin substrate had a noticeable effect on the selective production. Overall, this study explored the structural characteristics of CuO/CNT catalysts and their implications for lignin conversion and offered an efficient oxidation approach that holds promise for sustainable biorefining practices.

Design and Understanding of Adaptive Hydrogenation Catalysts Triggered by the H2/CO2-Formic Acid Equilibrium.

An adaptive catalytic system for selective hydrogenation was developed exploiting the H2+CO2HCOOH equilibrium for reversible, rapid, and robust on/off switch of the ketone hydrogenation activity of ruthenium nanoparticles (Ru NPs). The catalyst design was based on mechanistic studies and DFT calculations demonstrating that adsorption of formic acid to Ru NPs on silica results in surface formate species that prevent C═O hydrogenation. Ru NPs were immobilized on readily accessible silica supports modified with guanidinium-based ionic liquid phases (Ru@SILPGB) to generate in situ sufficient amounts of HCOOH when CO2 was introduced into the H2 feed gas for switching off ketone hydrogenation while maintaining the activity for hydrogenation of olefinic and aromatic C═C bonds. Upon shutting down the CO2 supply, the C═O hydrogenation activity was restored in real time due to the rapid decarboxylation of the surface formate species without the need for any changes in the reaction conditions. Thus, the newly developed Ru@SILPGB catalysts allow controlled and alternating production of either saturated alcohols or ketones from unsaturated substrates depending on the use of H2 or H2/CO2 as feed gas. The major prerequisite for design of adaptive catalytic systems based on CO2 as trigger is the ability to shift the H2+CO2HCOOH equilibrium sufficiently to exploit competing adsorption of surface formate and targeted functional groups. Thus, the concept can be expected to be more generally applicable beyond ruthenium as the active metal, paving the way for next-generation adaptive catalytic systems in hydrogenation reactions more broadly.

Integration of metabolomic and transcriptomic analyses reveals novel regulatory functions of the ChREBP transcription factor in energy metabolism.

Carbohydrate Response Element-Binding Protein (ChREBP) is a transcription factor that activates key genes involved in glucose, fructose, and lipid metabolism in response to carbohydrate feeding, but its other potential roles in metabolic homeostasis have not been as well studied. We used liver-selective GalNAc-siRNA technology to suppress expression of ChREBP in rats fed a high fat/high sucrose diet and characterized hepatic and systemic responses by integrating transcriptomic and metabolomic analyses. GalNAc-siChREBP-treated rats had lower levels of multiple short-chain acyl CoA metabolites compared to rats treated with GalNAc-siCtrl containing a non-targeting siRNA sequence. These changes were related to a sharp decrease in free CoA levels in GalNAc-siChREBP treated-rats, accompanied by lower expression of transcripts encoding enzymes and transporters involved in CoA biosynthesis. These activities of ChREBP likely contribute to its complex effects on hepatic lipid and energy metabolism. While core enzymes of fatty acid (FA) oxidation are induced by ChREBP knockdown, accumulation of liver acylcarnitines and circulating ketones indicate diversion of acetyl CoA to ketone production rather than complete oxidation in the TCA cycle. Despite strong suppression of pyruvate kinase and activation of pyruvate dehydrogenase, pyruvate levels were maintained, likely via increased expression of pyruvate transporters, and decreased expression of lactate dehydrogenase and alanine transaminase. GalNAc-siChREBP treatment increased hepatic citrate and isocitrate levels while decreasing levels of distal TCA cycle intermediates. The drop in free CoA levels, needed for the 2-ketoglutarate dehydrogenase reaction, as well as a decrease in transcripts encoding the anaplerotic enzymes pyruvate carboxylase, glutamate dehydrogenase, and aspartate transaminase likely contributed to these effects. GalNAc-siChREBP treatment caused striking increases in PRPP and ZMP/AICAR levels, and decreases in GMP, IMP, AMP, NaNM, NAD(P), and NAD(P)H levels, accompanied by reduced expression of enzymes that catalyze late steps in purine and NAD synthesis. ChREBP suppression also increased expression of a set of plasma membrane amino acid transporters, possibly as an attempt to replenish TCA cycle intermediates. In sum, combining transcriptomic and metabolomic analyses has revealed regulatory functions of ChREBP that go well beyond its canonical roles in control of carbohydrate and lipid metabolism to now include mitochondrial metabolism and cellular energy balance.

Enhancing the ketonization efficiency of biomass through selective conversion of furanic compounds

Catalytic ketonization of biomass is an effective approach for the deoxygenation of bio-oil and the enrichment of high-purity ketone products. However, the bio-oil contains a large amount of furanic components with oxygenated side groups (e.g., furfural, furfuralcohol, etc.), which severely hinders the efficiency of the ketonization reaction. In response to this challenge, this study employed Pd-based catalysts for selective conversion of furfural into "keto-friendly" components, thereby mitigating their inhibitory effects. Initially, three morphologies of CeO2 (the main catalyst for ketonization) were selected to investigate their influence on furfural conversion. It was found that the products were mainly furfural (exceeding 86 %), with only up to approximately 13 % of "keto-friendly" products (mainly furans) detected, indicating that pure CeO2 exhibits a weak catalytic effect on the effective conversion of furfural. Compared with pure CeO2, the yield of "keto-friendly" products increased significantly when 1 wt% Pd was loaded, demonstrating the excellent catalytic performance of Pd in the effective conversion of furfural. Co-doping of Pd and Zr (5 wt%) on CeO2 further increased the "keto-friendly" products to 66 %, suggesting a synergistic effect of Pd and Zr. Mechanism analysis revealed that Pd promotes the formation of furans and benzenes by enhancing the decarbonylation of furfural and subsequent furan ring opening reactions, while the competing carbonyl hydrogenation pathway is weakened. The findings of this study will be beneficial for enhancing the biomass ketonization conversion, thereby providing valuable references for the high-value utilization of biomass.

A structural and functional model for alkene dioxygenases

In this article, we report sterically-controlled iron sites based on non-chelating bulky imidazole ligands. Adding 6 equiv. of 1,2-dimethylimidazole (1,2-Me2Im) to Fe(OTf)2⋅2CH3CN affords the first example of a 5-coordinate imidazole‑iron complex ([Fe(1,2-Me2Im)5](OTf)2, 1). The structure is distorted square pyramidal (τ5 = 0.41). When an iPr group is substituted for the methyl group at the 2-position on the imidazole (2-iPr-1-MeIm), the 14-electron complex ([Fe(2-iPr-1-MeIm)4](OTf)2, 2) is obtained. This complex exhibits slightly distorted tetrahedral geometry (τ'4 = 0.93) with four N-donors and serves as a 4-His iron structural model complex for carotenoid cleavage dioxygenases (CCD). The electronic structure of 1 and 2 were characterized by Mössbauer spectroscopy. Reactions of 1 and 2 with model olefin substrates (1-R-4-(1-methoxyprop-1-en-2-yl)benzene; R = Me or Br) in the presence of oxygen result in olefin cleavage yielding ketone and aldehyde products, although 2 yields more products than 1. Support for a proposed reaction mechanism for 2 is offered from Density Functional Theory (DFT) calculations.

N-heterocyclic carbene-catalyzed nucleophilic aromatic substitution reaction of polyfluoroarenes

Fluorinated asymmetric aryl ketones represent a pivotal class of organic synthesis intermediates, which have garnered widespread application in the realms of organic chemistry, materials science, and drug discovery. Herein, we report a pioneering nucleophilic aromatic substitution (S N Ar) reaction involving aryl aldehydes and polyfluoroarenes, elegantly catalyzed by N-heterocyclic carbene (NHC). This innovative strategy yields bis(hetero)aryl ketone products in yields ranging from moderate to exceptional (40–83%), all achieved under gentle conditions, devoid of both transition metals and directing groups. The versatility of this method is underscored by its compatibility with a broad spectrum of substrates, particularly exhibiting remarkable resilience toward alkoxy functional groups. Notably, we have successfully transformed an array of biologically active molecules, crafting a series of their corresponding derivatives with precision.

Intrinsic promotion mechanism of calcium oxide on ketone production during catalytic fast pyrolysis of biomass via experiment and density functional theory simulation

CaO modified with acetic acid solution or sodium hydroxide (H-CaO/OH-CaO) was used to explore the relationship between the physical and chemical properties of CaO and the components of bio-oil during the pyrolysis of rice straw (RS) and model compounds via experiment and density functional theory(DFT) simulation. The results showed that the modification changed the properties of CaO, and thus the catalytic performance on production of bio-oil components. H-CaO with the larger number of strong basic sites (1.10 ∼ 2 times than commercial CaO) and the longer Ca-O bond length showed the better selectivity and performance on formation of ketones (the maximum relative content in bio-oil reached 43 %). The conversion pathway of cellulose/hemicellulose was changed by H-CaO, which promoted the formation of ketones. The easier combining of H-CaO with the pyrolysis primary products due to the longer Ca-O bond was the key to its better performance.

Harnessing the potential of acyl triazoles in bifunctional cobalt-catalyzed radical cross-coupling reactions

Persistent radicals facilitate numerous selective radical coupling reactions. Here, we have identified acyl triazole as a new and versatile moiety for generating persistent radical intermediates through single-electron transfer processes. The efficient generation of these persistent radicals is facilitated by the formation of substrate-coordinated cobalt complexes, which subsequently engage in radical cross-coupling reactions. Remarkably, triazole-coordinated cobalt complexes exhibit metal-hydride hydrogen atom transfer (MHAT) capabilities with alkenes, enabling the efficient synthesis of diverse ketone products without the need for external ligands. By leveraging the persistent radical effect, this catalytic approach also allows for the development of other radical cross-coupling reactions with two representative radical precursors. The discovery of acyl triazoles as effective substrates for generating persistent radicals and as ligands for cobalt catalysis, combined with the bifunctional nature of the cobalt catalytic system, opens up new avenues for the design and development of efficient and sustainable organic transformations.

Influence of Carbohydrate Intake on Caprylic Acid (C8:0)-Induced Ketogenesis-A Systematic Review and Meta-Analysis.

The ketogenic diet is used worldwide to treat various diseases, especially drug-resistant epilepsies. Medium-chain triglycerides or medium-chain fatty acids, primarily the major ketogenic compound caprylic acid (C8; C8:0), can significantly support ketogenesis. This review examines the effects of concurrent carbohydrate intake on C8-induced ketogenesis. A systematic literature search (PubMed and Web of Science) with subsequent data extraction was performed according to PRISMA guidelines and the Cochrane Handbook. Studies investigating the metabolic response to C8-containing MCT interventions with carbohydrate intake were included. The studies did not include a ketogenic diet. Three intervention groups were created. The quality of the studies was assessed using the RoB II tool, and the meta-analysis was performed using the Cochrane RevMan software. A total of 7 trials, including 4 RCTs, met the inclusion criteria. Ketone production was lower when C8 was combined with carbohydrates compared to MCT intake alone. The lower C8 dose group (11 g) did not show a significantly lower ketogenic effect than the higher dose group (19 g). Forest plot analysis showed heterogeneous data. The data suggest a non-linear relationship between C8, carbohydrate intake and ketone production. Further studies are needed to investigate the influence of different carbohydrates on C8-induced ketogenesis. Limitations include heterogeneous intervention conditions, such as different types of dispersions, caffeine intake, limited number of studies and variability in study design.

Continuous Flow Approach for Benzylic Photo-oxidations Using Compressed Air.

A continuous flow approach for the aerobic photo-oxidation of benzylic substrates to ketone and aldehyde products is presented. The resulting process exploits UV-A LEDs (375 nm) in combination with a Corning AFR reactor that ensures effective gas-liquid mixing and leads to short residence times of 1 min. A variety of benzylic substrates are converted to their corresponding carbonyl products, and scalability is demonstrated to produce multigram quantities of products within a few hours. Overall, this continuous flow approach offers several improvements over alternative oxidation methods due to the combined use of air as an oxidant and SAS (sodium anthraquinone-2 sulfonate) as a water-soluble photocatalyst. The use of greener and safer conditions together with process intensification principles renders this flow approach attractive for further industrial applications.

Upgrade of Acetone-Butanol-Ethanol Mixture to High-Value Biofuels over Ca-Doped Ni-CaO-SiO2 catalyst.

The selective conversion of biomass fermentation derived from an acetone-butanol-ethanol (ABE) mixture into high-value biofuels is of paramount importance for industrial applications. However, challenges persist in effectively controlling the selectivity of long carbon chain ketones in elevated ABE conversion. In this research, a Ca-doped Ni-CaO-SiO2 catalyst was designed and employed to achieve a remarkable conversion of 89.9% into ketone products from the extracted ABE mixture. The selectivity for C8+ ketones reaches 41.8%, demonstrating exceptional performance. The reversible phase transition between Ca2SiO4 and CaCO3 enhances the recyclability, thereby improving the sustainability of the process. Additionally, the trace intermediate 3-hepten-2-one was successfully detected using two-dimensional GC×GC-MS, elucidating the conversion pathway in the catalytic upgrading of the ABE mixture. This finding offers a potential route for the efficient utilization of biomass and the highly selective production of value-added chemicals.