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Although numerous observational studies associated underfeeding with poor outcome, recent randomized controlled trials (RCTs) have shown that early full nutritional support does not benefit critically ill patients and may induce dose-dependent harm. Some researchers have suggested that the absence of benefit in RCTs may be attributed to overrepresentation of patients deemed at low nutritional risk, or to a too low amino acid versus non-protein energy dose in the nutritional formula. However, these hypotheses have not been confirmed by strong evidence. RCTs have not revealed any subgroup benefiting from early full nutritional support, nor benefit from increased amino acid doses or from indirect calorimetry-based energy dosing targeted at 100% of energy expenditure. Mechanistic studies attributed the absence of benefit of early feeding to anabolic resistance and futile catabolism of extra provided amino acids, and to feeding-induced suppression of recovery-enhancing pathways such as autophagy and ketogenesis, which opened perspectives for fasting-mimicking diets and ketone supplementation. Yet, the presence or absence of an anabolic response to feeding cannot be predicted or monitored and likely differs over time and among patients. In the absence of such monitor, the value of indirect calorimetry seems obscure, especially in the acute phase of illness. Until now, large feeding RCTs have focused on interventions that were initiated in the first week of critical illness. There are no large RCTs that investigated the impact of different feeding strategies initiated after the acute phase and continued after discharge from the intensive care unit in patients recovering from critical illness., SCOPUS: re.j, info:eu-repo/semantics/published

Diet-induced nutritional changes in the maternal reproductive tract elicit embryonic adaptations to maintain growth and survival, changes which nonetheless compromise long-term child and adult health via developmental programming. This is plausibly facilitated by metaboloepigenetic mechanisms, whereby metabolic sensing of nutrient availability coordinates epigenetic regulation of gene expression in a developmentally persistent manner, affecting short- and long-term embryo physiology and health. Despite little evidence for its efficacy and developmental safety, the very high fat, low carbohydrate ketogenic diet (KD) is increasing in popularity as a ‘fertility diet’ worldwide. In line with the hypothesis that metaboloepigenetics links diet with embryo health, KD consumption elevates systemic concentrations of the ketones beta-hydroxybutyrate (BOHB) and acetoacetate (AcAc), which in addition to their role as oxidative fuels, are epigenetic modifiers and may consequently affect embryo development. Therefore, to investigate the safety of a periconceptional KD for offspring health, it is necessary to determine the impact of ketones on the development, physiology, and viability of the preimplantation embryo. Using a mouse model, the impact of in vitro ketone exposure on preimplantation embryo development, physiology and viability was assessed. Exposure to BOHB alone perturbed blastocyst development, decreased glucose metabolism, and increased histone acetylation, predominantly impacting the trophectoderm cell lineage. This was further associated with implantation failure and delayed female fetal development post-transfer, suggesting preimplantation BOHB exposure is detrimental to development in a female-specific manner via a trophectoderm-mediated mechanism. Similarly, in vitro exposure to AcAc alone or AcAc + BOHB in combination did not impair morphological development of the blastocyst, however impacted glucose metabolism and cumulatively increased histone acetylation. P

The diastereo- and enantioselective allylation of ketones remains a synthetic challenge, with transition metal catalysis offering the most applied methods. Here, a boron-catalyzed allylation of ketones with allenes is presented. Excellent yield, regioselectivity, and diastereoselectivity were found across functionalized substrates. The reaction was further developed to accommodate an enantioenriched boron catalyst and thus gave asymmetric ketone allylation in good yield, diastereoselectivity, and enantioselectivity. Mechanistic studies supported a hydroboration–allylation–transborylation pathway.

Scope Milk fat globule membrane (MFGM) is an important component of milk that has previously been removed in the manufacture of infant formulas, but has recently gained attention owing to its potential to improve immunological, cognitive, and metabolic health. The goal of this study is to determine whether supplementing MFGM in infant formula would drive desirable changes in metabolism and gut microbiota to elicit benefits observed in prior studies. Methods and Results The serum metabolome and fecal microbiota are analyzed using H-1 NMR spectroscopy and 16S rRNA gene sequencing respectively in a cohort of Chinese infants given a standard formula or a formula supplemented with an MFGM-enriched whey protein fraction. Supplementing MFGM suppressed protein degradation pathways and the levels of insulinogenic amino acids that are typically enhanced in formula-fed infants while facilitating fatty acid oxidation and ketogenesis, a feature that may favor brain development. MFGM supplementation did not induce significant compositional changes in the fecal microbiota but suppressed microbial diversity and altered microbiota-associated metabolites. Conclusion Supplementing MFGM in a formula reduced some metabolic gaps between formula-fed and breastfed infants.

Prevention of epilepsy and its progression remains the most urgent need for epilepsy research and therapy development. Novel conceptual advances are required to meaningfully address this fundamental challenge. Maladaptive epigenetic changes, which include methylation of DNA and acetylation of histones - among other mechanisms, are now well recognized to play a functional role in the development of epilepsy and its progression. The methylation hypothesis of epileptogenesis suggests that changes in DNA methylation are implicated in the progression of the disease. In this context, global DNA hypermethylation is particularly associated with chronic epilepsy. Likewise, acetylation changes of histones have been linked to epilepsy development. Clinical as well as experimental evidence demonstrate that epilepsy and its progression can be prevented by metabolic and biochemical manipulations that target previously unrecognized epigenetic functions contributing to epilepsy development and maintenance of the epileptic state. This review will discuss epigenetic mechanisms implicated in epilepsy development as well as metabolic and biochemical interactions thought to drive epileptogenesis. Therefore, metabolic and biochemical mechanisms are identified as novel targets for epilepsy prevention. We will specifically discuss adenosine biochemistry as a novel therapeutic strategy to reconstruct the DNA methylome as antiepileptogenic strategy as well as metabolic mediators, such as beta-hydroxybutyrate, which affect histone acetylation. Finally, metabolic dietary interventions (such as the ketogenic diet) which have the unique potential to prevent epileptogenesis through recently identified epigenetic mechanisms will be reviewed. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.

Objective: High-anion gap metabolic acidosis (HAGMA) most commonly results from excess urea, lactate, ketones and exposure to toxins such as salicylate and toxic alcohols. Accumulation of pyroglutamic acid (PGA) is a rare cause of HAGMA. The exact incidence of HAGMA caused by PGA accumulation is unknown. A recent prospective study reported that high urine PGA concentrations were associated with 10% of patients with HAGMA. PGA is processed by the glutamate-glutathione cycle. The commonest cause of PGA accumulation is glutathione depletion. This causes the loss of negative feedback on gamma-glutamylcysteine (PGA precursor) production. Other causes include malnutrition, alcoholism, liver failure and sepsis. Though rare, deficiency of either glutathione synthetase causing gamma-glutamylcysteine (PGA precursor) accumulation or 5-oxoprolinase resulting in reduced PGA metabolism, also cause PGA accumulation. We describe a case of confirmed PGA accumulation after repeated supratherapeutic paracetamol use. Case report: A 32-year-old female presented with ongoing pain from shingles despite having taken 96 x 665 mg modified-release paracetamol caplets over the preceding two days. Two years prior, she suffered a gastric ulcer perforation following excessive ibuprofen use for dysmenorrhea. She subsequently ceased using NSAIDs and substituted these with regular use of four modifiedrelease paracetamol tablets every 3-4 hours. On presentation vital signs were normal except a respiratory rate of 24/min. Venous blood gas showed pH 7.04, bicarbonate 5.0mmol/L, pCO2 19 mmHg, lactate 1.4mmol/L, sodium 150mmol/L, chloride 117 mmol/L and anion gap 28, indicating a partially compensated HAGMA. Serum ketones were 2.8mmol/L, salicylate undetected and normal osmolar gap. Serum paracetamol was 312 mumol/L, 2.5 hours after the last dose. Liver function, INR and creatinine were normal. PGA accumulation from chronic paracetamol misuse and glutathione depletion was suspected. Acetylcysteine was in

A facile and convenient synthesis of the chiral phthalide framework catalyzed by cationic iridium was developed. The method utilized cationic iridium/bisphosphine-catalyzed asymmetric intramolecular carbonyl hydroacylation of 2-keto benzaldehydes to furnish the corresponding optically active phthalide products in good to excellent enantioselectivities (up to 98% ee). The mechanistic studies using a deuterium-labelled substrate suggested that the reaction involved an intramolecular carbonyl insertion mechanism to iridium hydride intermediate. In addition, we investigated the kinetic isotope effect (KIE) of intramolecular hydroacylation with deuterated substrate and determined that the C-H activation step is not included in the turnover-limiting step.

A facile and convenient synthesis of the chiral phthalide framework catalyzed by cationic iridium was developed. The method utilized cationic iridium/bisphosphine-catalyzed asymmetric intramolecular carbonyl hydroacylation of 2-keto benzaldehydes to furnish the corresponding optically active phthalide products in good to excellent enantioselectivities (up to 98% ee). The mechanistic studies using a deuterium-labelled substrate suggested that the reaction involved an intramolecular carbonyl insertion mechanism to iridium hydride intermediate. In addition, we investigated the kinetic isotope effect (KIE) of intramolecular hydroacylation with deuterated substrate and determined that the C-H activation step is not included in the turnover-limiting step.

Introduction: Very Low Calorie Diets (VLCD) have been demonstrated to achieve rapid and significant weight loss in obese people without kidney disease. However, there is no published evidence on the use of VLCD in end-stage kidney disease (ESKD) patients. Current manufacturers' guidelines state the meal replacement VLCD are contra-indicated in patients with impaired kidney function (eGFR <60ml/min). The aim of the study is to determine if the use of a VLCD with 3 meal replacements is safe and effective for weight loss in patients with ESKD treated with haemodialysis (HD). Method(s): 22 HD patients (9 home HD, 13 centre HD) with BMIs >30 were recruited and consented to the study. All were placed on a VLCD of 600-800 kcals. Subjects were monitored weekly for 4 weeks, and then fortnightly for the remainder of the study period (12 weeks in total). Pre and post dialysis weight, intradialytic fluid gain, biochemistry, ketones, and compliance with the VLCD plan were monitored each visit by nursing staff and dietitians. Dialysis prescriptions and medications were altered as medically required. Nutritional assessments, quality of life surveys, waist measurements, transthyretin and HbA1c were collected at baseline and completion of the study. Data was assessed using paired t-test and a mixed models where appropriate. All patients were included in the analysis. Result(s): Of the 22 patients recruited, 19 patients completed the 12 week treatment course. Three patients withdrew as they were found it difficult to maintain the study meal plans (at week 5, 6 and 10). Mean age was 49.7 years (SD 7.4), 40.1% were female, and 45.5% diabetic. Home HD patients were treated with alternate days HD 8 hours while centre HD were treated with 5 hour sessions 3 times per week. Mean pre dialysis weight was 121.1 kg (SD 28.4) at baseline. Throughout the study period pre-dialysis weight declined by 0.91 kg per week (95% C.I. 0.74 - 1.08, p<0.001). When assessed according to dialysis modality, rat

A new catalytic system that employs water as an environmentally friendly solvent for the dehydrogenative oxidation of alcohols and lactonization of diols has been developed. In this catalytic system, a water-soluble dicationic iridium complex having a functional ligand that comprises α-hydroxypyridine and 4, 5-dihydro-1H-imidazol-2-yl moieties exhibits high catalytic performance. For example, the catalytic dehydrogenative oxidation of 1-phenylethanol in the presence of 0.25 mol % of the iridium catalyst and base under reflux in water proceeded to give acetophenone in 92% yield. Additionally, under similar reaction conditions, the iridium-catalyzed dehydrogenative lactonization of 1, 2-benzenedimethanol gave phthalide in 98% yield.

Petroleum and its derivatives revolutionized every aspect of human life, from how we work and travel to what we wear and eat. However, mitigation and prevention of climate change are of utmost ethical and economical importance. Biology is a potential means for reducing greenhouse gas emissions, while maintaining or even diversifying and improving the goods and services the world has grown to depend on. Biofuels, for example, can be made with renewable waste feedstocks and can supplement or replace petroleum-derived fuels but lack optimal molecular properties. We therefore sought a means for customizing biologically-produced carbon backbones. To this end, we engineered enzymes from microbial antibiotic biosynthesis called polyketide synthases. These enzymes form modular “assembly lines” where the activity of each catalytic unit can be predicted with reasonable confidence. We envisioned combining individual enzymes to form a new biosynthetic assembly line which, until this work, did not exist in nature. We first investigated the main biosynthetic chassis, an iterative polyketide synthase, BorM5, from the borrelidin pathway. We discovered that BorM5 is promiscuous for both starting and elongation substrates, producing a variety of mid-length branched and linear saturated fatty acyl intermediates. We next characterized the trans-acting thioesterase, BorB, hoping to use it as an offloading mechanism. We propose that BorB acts to remove dead-end intermediates from the borrelidin pathway, increasing its efficiency. We then engineered on- and off-loading neighbors for BorM5 and observed production of new-to-Nature C11 and C14 methyl branched methyl ketones. Diversification and high-titer production of these compounds, combined with materials testing, may lead to improved biofuels and the environmental, economic, and social benefits that accompany them.

This work presents a formalised, physically consistent approach to account for cross association in the SAFT framework. The focus of the approach was to account for solvation of non-self-associating components, using members of the ketone and ether functional groups as model components. Physical consistency is captured by only considering a single negative site in these components, with the association mechanisms termed the “N scheme” as a result. An accurate polar parameter set is a prerequisite for the approach, where polar and dispersion interactions are already accounted for in pure component properties and those of mixtures where solvation is absent. Using SAFT-VR Mie-GV as the example framework, the approach considers the discretisation of the two association parameters, and it applies the resulting matrix of parameter sets to mixture VLE data for the ketone or ether with alcohols in the C2 to C4 range. Analysis of the resulting AAD contour plots demonstrate that the use of average solvation parameters for each functional groups are appropriate, rather than component-specific parameters, and they offer excellent pure predictions for alcohol mixtures and good predictions for aqueous mixtures. As a final test, the approach was applied to chloroform, considering a single positive site and using the proposed parameterisation method. The resulting “P scheme” for chloroform, in conjunction with the N scheme for acetone, yields excellent predictions for the quintessential chloroform/acetone mixture and emphasises the suitability and predictive strength of the approach.

The DIPSkewphos/PICA derivative-Ru(II) complexes catalyzed asymmetric hydrogenation of significantly sterically hindered 2',3',4',5',6'-pentamethylacetophenone, which was not reduced with NaBH4 at 25 degrees C, with a substrate-to-catalyst molar ratio (S/C) of 2000 under 50 atm of H-2 in a base-containing 2-propanol to afford the alcohol in 99% ee quantitatively. A series of polysubstituted aromatic ketones was smoothly reacted with an S/C of 300-10,000 under 10-50 atm of H-2, yielding the alcoholic products in up to 99% ee. The catalyst system achieved an industrial-scale (50 kg) hydrogenation of 2',6'-dichloro-3'-fluoroacetophenone, affording the alcohol in 96% isolated yield and in 98% ee. The obtained alcoholic product is known as a key intermediate for the synthesis of the medicine crizotinib.

Palladium-catalyzed reactions have become one of the most important tools in modern organic chemistry due to its ability to catalyze the formation of new carbon-carbon bonds. The aim of the work presented in this thesis was to develop new palladium(II)-catalyzed addition reactions. In this work, cyanamides were investigated as a new substrate to give aryl amidines as products. The first protocol developed employed aryltrifluoroborates as the aryl partner, and the insertion of the aryl group into un-, mono-, and di-substituted cyanamides was successful for a wide variety of aryltrifluoroborates. An alternative method of generating the necessary intermediate for insertion into the cyanamide is the decarboxylative formation of aryl-palladium from aryl carboxylic acids. A protocol was developed for this reaction, but was unfortunately limited to a small number of ortho-substituted electron-rich aryl carboxylic acids. The mechanism was investigated by the means of DFT calculations and ESI-MS studies, and the rate-determining step was suggested to be the 1,2-carbopalladation based upon those results. A translation of the batch protocol to continuous-flow conditions was also demonstrated. The ideal method of generating the aryl-palladium species is by C-H bond activation, and this approach was demonstrated with indoles, giving a variety of 3-amidinoindoles as products. The mechanism was investigated by DFT calculations and a plausible catalytic cycle was proposed. A continuous-flow application of a desulfitative palladium(II)-catalyzed addition to nitriles to give ketones was developed. In addition, different reactor materials were evaluated in the microwave heated reactor cavity. Thus the reaction was shown to proceed with microwave heating in a borosilicate glass and an aluminum oxide reactor, and also in conditions mimicking conventional heating in a silicon carbide reactor. Finally, a protocol was developed for the convenient synthesis of sodium aryl sulfinates from Gr

ObjectiveThe ketogenic diet (KD) is a proven treatment for drug-resistant (DR) seizures in children and adolescents. However, the relationship between seizure control and the most commonly measured metabolite of the diet, the ketone body d-beta-hydroxybutyrate (D-BHB), is controversial. This study was performed to clarify the relationship because specific ketone bodies may be useful as biomarkers of diet efficacy.MethodsFamilies of children with DR seizures were approached for participation in this open-label, prospective study when they were referred for the KD at two western Canadian children's hospitals. Inclusion criteria included documentation of DR seizures without exclusion based on age, sex, seizure, or syndrome type. Patients were excluded if they were referred for treatment of a metabolic disorder independent of seizures. Seizures were quantified via parental report and standardized as seizure frequency per 28 days. Epilepsy syndromes were identified on the basis of the medical record. Blood D-BHB was determined by tandem mass spectrometry.ResultsA total of 23 patients were recruited from both sites. Data from five individuals were excluded because these seizures occurred in clusters, leaving 18 patients for the primary analysis. In the latter group, a clear positive correlation was present between measures of seizure frequency and D-BHB concentrations. However, this failed to reach statistical significance, likely because of the relatively small numbers.SignificanceA trend clearly exists between seizure frequency and D-BHB levels, so we should not be dissuaded by the lack of statistical significance because it possibly results from methodological techniques, especially sample size. These results call for a larger prospective study in which seizure frequency is assessed at the point of care in a standardized fashion so as to determine whether D-BHB can be used as a reliable biomarker of KD efficacy.

The volatile fraction of dehydrated edible seaweeds belonging to seven species (Himanthalia elongata, Laminaria ochroleuca, Palmaria palmata, Porphyra umbilicalis, Saccharina latissima, Ulva lactuca and Undaria pinnatifida) was analyzed by gas chromatography–mass spectrometry, after solid-phase microextraction of samples. Thirty-six hydrocarbons, 34 ketones, 28 aldehydes, 23 alcohols, 8 carboxylic acids, 6 halogenated compounds, 4 furans, 3 esters, 2 sulphur compounds, 2 pyrazines, 1 pyridine and 1 amine were detected among the 151 volatile compounds found in seaweeds. There were significant differences between seaweed species for all the volatile compounds. Hydrocarbons reached their highest levels in U. pinnatifida, ketones in P. umbilicalis, aldehydes in P. palmata and P. umbilicalis, alcohols in P. umbilicalis, carboxylic acids in S. latissima, and halogenated compounds in L. ochroleuca and S. latissima. Sensory analysis revealed that P. palmata, U. lactuca and H. elongata were the seaweeds showing the most potent seafood odour and seaweed odour characteristics. © 2016 Elsevier Ltd

Ketosis is a metabolic condition that occurs during heat stress, prolonged exercise, fasting, and in obese and diabetic individuals. The major ketone body, β-OH butyrate, affects cellular signaling pathways in a hormone-like manner through its receptor GPR109a. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of diabetes. To understand how β-OH butyrate signaling affects hepatic metabolism we compared the fasting response in control and 3-hydroxy-3-methylglutaryl-CoA Synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production, and in GPR109a +/+ and -/- mice. To directly assess the response to ketone signaling we gave intraperitoneal injections of the GPR109a agonists niacin (0.8mmol/kg) and β-OH butyrate (5.7mmol/kg) to HMGCS2 knockdown mice over the final 9 hours of a 16 hour fast. Ketogenic deficient mice showed a more robust increase in hepatic carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 2 (UCP2) mRNA than control mice in response to fasting. Accordingly, niacin and β-OH butyrate administration decreased fasting CPT1 mRNA expression in knockdown mice, while fasting knockdown UCP2 mRNA and control HMGCS2 mRNA were lowered by β-OH butyrate. GPR109a knockout did not alter the hepatic response to fasting, although the effect of niacin on fasting HMGCS2 mRNA expression was dependent on GPR109a expression. While the role of GPR109a and how chronic hyperketonemia alters β-OH butyrate signaling require further study, these data suggest that endogenous β-OH butyrate signaling during a fast regulates the transcript levels of hepatic genes directly involved in its own synthesis.

Palladium complexes have the ability to catalyse cross-coupling of two organic moieties through the formation of transient metal-carbon bonds, thus bringing them closer to each other to facilitate the formation of a new bond. Palladium-catalysed coupling reactions are one of the most important carbon-carbon forming reactions available to organic chemists and many of these reactions rely on the reactivity of aryl-palladium complexes. The investigation of new aryl-palladium precursors is thus of great interest, especially as more sustainable and economic methods can be developed. This thesis describes the use of carboxylic acids and sodium arylsulfinates as such new arylating agents. Protocols for microwave-assisted palladium(II)-catalysed decarboxylative synthesis of electron-rich styrenes and 1,1-diarylethenes were developed. However, these transformations had very limited substrate scopes which prompted the investigation of sodium arylsulfinates as alternative arylating agents. These substrates were employed in the microwave-assisted palladium(II)-catalysed desulfitative addition to nitriles, and the substrate scope was demonstrated by combining a wide array of sodium arylsulfinates and nitriles to yield the corresponding aryl ketones. The application of the desulfitative reaction in a continuous flow setup was demonstrated, and aluminium oxide was identified as safe alternative to borosilicate glass as a reactor material. The mechanisms of the decarboxylative and desulfitative transformations were investigated by density functional theory (DFT) calculations. The desulfitative reaction was also investigated by direct electrospray ionization mass spectrometry (ESI-MS), providing further mechanistic insight. Finally, a protocol for the safe and convenient synthesis of a wide range of sodium arylsulfinates was developed.

Leucine amino acid, has been explored as an effective catalyst for conversion of ketones and aldehydes into corresponding gem-dihydroperoxides using 30% aqueous hydrogen peroxide in acetonitrile at room temperature. The reactions proceed smoothly within short periods of time to provide the respective gem-dihydroperoxides in excellent yields. Mild reaction conditions, low reaction times, high yields, low environmental impact, use of non-expensive, recyclable and green catalyst are the main merits of the present method.

The large consumption of freshwater in fermentations and bio-transformations is a matter of concern for the sustainability of many bio-processes. The use of seawater to perform bio-processes is a sustainable alternative. In this work, we used marine yeasts from deep-sub-seafloor sediments grown in seawater as bio-catalysts to perform the stereoselective reduction of different ketones, and the bio-transformations were accomplished in seawater as well. Strains of Meyerozyma guilliermondii and Rhodotorula mucilaginosa were able to reduce different aromatic ketones with high molar conversions and moderate-to-high enantioselectivity with no significant differences between bio-catalysis performed in seawater and freshwater. Finally, the selected marine yeasts were used for the reduction of key intermediates in seawater for the synthesis of molecules of pharmaceutical interest (desogestrel, norgestrel, gestodene, pramipexole).

A simple and efficient conversion of ketones and aldehydes into corresponding gem-dihydroperoxides (DHPs) has been developed by SbCl3-catalyzed oxidation with 30% H2O2 at room temperature. The reactions proceeded smoothly under mild conditions at room temperature. Simple experimental procedure, use of inexpensive and non-toxic catalyst, high yields and low reaction times are the main merits of the present method.

The work described in this thesis is focused on the development of new bidentate iridium complexes and their applications in the asymmetric reduction of olefins, ketones and imines. Three new types of iridium complexes were synthesized, which included pyridine derived chiral N,P-iridium complexes, achiral NHC complexes and chiral NHC-phosphine complexes. A study of their catalytic applications demonstrated a high efficiency of the N,P-iridium complexes for asymmetric hydrogenation of olefins, with good enantioselectivity. The carbene complexes were found to be very efficient hydrogen transfer mediators capable of abstracting hydrogen from alcohols and subsequently transfer it to other unsaturated bonds. This hydrogen transferring property of the carbene complexes was used in the development of C–C and C–N bond formation reactions via the hydrogen borrowing process. The complexes displayed high catalytic reactivity using 0.5–1.0 mol% of the catalyst and mild reaction conditions. Finally chiral carbene complexes were found to be activated by hydrogen gas. Their corresponding iridium hydride species were able to reduce ketones and imines with high efficiency and enantioselectivity without any additives, base or acid., At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 5: Submitted. Paper 6: Manuscript.

It is well established that organic pollutants such as phenols are degraded in the presence of chromophoric dissolved organic matter (CDOM) and sunlight in natural waters. Early work attributed the photochemical loss of phenols to the involvement of photoproduced reactive oxygen species (ROS) such as singlet oxygen (1O2), hydroxyl radical (*OH) or peroxy radicals (RO2*). However, evidence for the involvement of triplet excited states of aromatic ketones/aldehydes within CDOM has accumulated in the literature. To probe the mechanism of the photosensitized loss of phenols by humic substances (HS), the dependence of the initial rate of 2,4,6-trimethylphenol (TMP) loss (RTMP) on dioxygen concentration and irradiation wavelength was examined both for a variety of untreated as well as borohydride-reduced HS and C18 extracts from the Delaware Bay and Mid-Atlantic Bight. The effect of [O2] and borohydride-reduction of SRFA was also examined for a series of substituted phenols of varying one-electron reduction potentials. We find that RTMP was inversely proportional to dioxygen concentration at [O2] > 50 μM, a dependence consistent with reaction with triplet excited states, but not with 1O2 or RO2. Modeling the dependence of RTMP on [O2] provided rate constants for TMP reaction, O2 quenching and lifetimes compatible with a triplet intermediate. Borohydride reduction significantly reduced TMP loss, supporting the role of aromatic ketone triplets in this process. However, for most samples, the incomplete loss of sensitization following borohydride reduction, as well as the inverse dependence of RTMP on [O2] for these reduced samples, suggests that there remains another class of oxidizing triplet sensitizer, perhaps quinones. However, the results of the wavelength dependence reveal that the sensitization is driven primarily by shorter wavelength UV-B and UV-A absorbing moieties, consistent with the involvement of aromatic ketones and aldehydes but appearing to exclude the

The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate "classic KD", as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD.

Cyclic secondary amines and 2-hydroxybenzaldehydes or related ketones react to furnish benzo[e][1,3]oxazine structures in generally good yields. This overall redox-neutral amine α-C-H functionalization features a combined reductive N-alkylation/oxidative α-functionalization and is catalyzed by acetic acid. In contrast to previous reports, no external oxidants or metal catalysts are required. Reactions performed under modified conditions lead to an apparent reductive amination and the formation of o-hydroxybenzylamines in a process that involves the oxidation of a second equivalent of amine. A detailed computational study employing density functional theory compares different mechanistic pathways and is used to explain the observed experimental findings. Furthermore, these results also reveal the origin of the catalytic efficiency of acetic acid in these transformations. © 2014 American Chemical Society.

Unsubstituted quinoxaline (I) reacts with dimedone, indanedione, and 1-phenyl-3-methylpyrazol-5-one in dimethylsulfoxide in the presence of acid to form monosubstitution products II-IV. Quinoxaline reacts with 1,3-dimethylbarbituric acid in dimethylsulfoxide solution at room temperature to form monosubstitution product V without external catalysis. Heating of I with resorcinol in ethanol in the presence of acid produced resorcinol derivative VI. In the presence of base, quinoxaline reacts with 1-phenyl-3-methylpyrazol-5-one to form dipyrazolylmethane VII and tetrapyrazolylethane derivative VIII. Compound VIII undergoes cleavage to form dipyrazolylmethane VII in dimethylformamide solution with boiling or in the presence of iodine at room temperature. © 2013 Springer Science+Business Media New York.

The effect of organic species on a solar-driven photo-Fenton treatment of a mixture of pesticides (methyl-oxydemethon, methidathion, carbaryl and dimethoate) has been studied in this paper. Triethoxyisododecyl alcohol, acetophenone and ethylenediaminetetraacetic acid (EDTA) have been used as examples of surfactants, solvents and complexing agents, respectively. An inhibitory effect on mineralization as well as on the elimination of the pesticides was observed in the case of the aliphatic surfactants, most probably due to the competition between the pesticides and the added organic matter for reaction with the relatively unselective hydroxyl radical. A methodology combining chemical analyses and bioassays was tested in order to explore the applicability of coupling a photo-Fenton process with a biological treatment in the presence of the surfactant. Despite the complexity of the mixture under study, a reliable monitoring of the process was accomplished; the biocompatibility of the mixture was enhanced and the optimal irradiation intensity was achieved just after complete removal of the pesticides. © 2011 Elsevier B.V.

Le vieillissement de la population est relié à l’augmentation de la présence de certaines maladies comme les déclins cognitifs ou les démences de type Alzheimer. Chez les personnes à risques de développer ces démences, une diminution précoce du métabolisme cérébral du glucose peut être observée avant même l’apparition des premiers symptômes. Ce déficit énergétique pourrait expliquer la cascade qui mène au développement des déclins cognitifs. Les cétones sont des molécules produites par le corps à partir de la lipolyse des acides gras qui ont déjà démontré leur efficacité comme substrat énergétique de substitution pour le cerveau. L’utilisation de triglycérides de moyennes chaînes (MCT), des acides gras facilement absorbables et oxydables, est un moyen efficace pour augmenter les cétones rapidement mais transitoirement. Notre objectif était de voir s’il était possible d’augmenter les cétones plasmatiques et de maintenir une concentration modérée sur 24 h avec une supplémentation quotidienne en MCT. Dix participants ont d’abord reçu une supplémentation de 2 semaines d’une émulsion de MCT (3 fois par jour). Leur concentration plasmatique de cétones mais aussi de glucose, de cholestérol, de triglycérides et d’acides gras libres était mesurée au début et à la fin de la supplémentation. Huit participants ont par la suite reçu une supplémentation de 4 semaines de l’émulsion de MCT (4 fois par jour). En plus des paramètres mentionnés précédemment, des mesures d’oxydation de MCT, à l’aide d’un traceur 13C-trioctanoate, d’oxydation des cétones, à l’aide d’un traceur de 13C-bêta-hydroxybutyrate ((30Hb), et des mesures de composition corporelle étaient effectuées. Dans les deux études, les analyses plasmatiques ont démontré une augmentation significative des cétones plasmatiques (jusqu’à 0,47 ± 0 ,1 5 mM), qui semblait plus soutenue lors de la deuxième étude. Aucune autre modification n’a été observée dans les analyses plasmatiques. Une diminution de l’oxydation du traceur 13C, Aging leads to the development of many diseases among which is cognitive decline associated with dementia and Alzheimer's disease (AD). In populations who are at risk of developing cognitive decline, it has been noted that a marked brain glucose hypometabolism precedes the onset of other clinical symptoms such as [beta]-amyloid accumulation. This hypometabolism could therefore be responsible for the development of AD. Ketone bodies are energetic molecules that are produced by the liver following the (3-oxidation of fatty acids. They already have been showed to be able to sustain brain metabolism as the principal energy source. Medium chain triglycerides (MCT) are easily absorbed and metabolised fatty acids. They can raise plasma ketones rapidly but transiently. Our objective was to determine whether it was possible to raise and maintain a moderate plasma ketone concentration over 24 h in healthy adults. Ten participants were first given a 2 week supplementation of MCT (3 times a day). Plasma ketone, glucose, cholesterol, triglyceride and free fatty acids were measured. Another 8 participants were given a 4 week supplementation of MCT (4 times a day). In addition to the measures taken in the first project, MCT oxidation; with [indice supérieur 13] C-trioctanoate, ketone oxidation; with [indice supérieur 13] C-beta-hydroxybutyrate and body composition were measured. In both projects, plasma ketone concentration were raised (to a maximum of 0.48 ± 0.15 mM) and appeared to be more stable in the second project. All other plasma measures were unchanged. Significantly lower [indice supérieur 13] C-trioctanoate oxidation was detected during the 2 to 5 hours following the tracer absorption after the supplementation and a marked augmentation was detected 24 h following the supplementation. This indicates a shift in MCT utilization by the body from immediate energy source to ketone precursor. No changes were noted in [beta]OHb oxidation or in body composition. These

Chemotherapy-induced neurotoxicity is a significant problem associated with successful treatment of many cancers. Tubulin is a well-established target of antineoplastic therapy; however, tubulin-targeting agents, such as paclitaxel and the newer epothilones, induce significant neurotoxicity. Eribulin mesylate, a novel microtubule-targeting analogue of the marine natural product halichondrin B, has recently shown antineoplastic activity, with relatively low incidence and severity of neuropathy, in metastatic breast cancer patients. The mechanism of chemotherapy-induced neuropathy is not well understood. One of the main underlying reasons is incomplete characterization of pathology of peripheral nerves from treated subjects, either from patients or preclinically from animals. The current study was conducted to directly compare, in mice, the neuropathy-inducing propensity of three drugs: paclitaxel, ixabepilone, and eribulin mesylate. Because these drugs have different potencies and pharmacokinetics, we compared them on the basis of a maximum tolerated dose (MTD). Effects of each drug on caudal and digital nerve conduction velocity, nerve amplitude, and sciatic nerve and dorsal root ganglion morphology at 0.25 × MTD, 0.5 × MTD, 0.75 × MTD, and MTD were compared. Paclitaxel and ixabepilone, at their respective MTDs, produced significant deficits in caudal nerve conduction velocity, caudal amplitude and digital nerve amplitudes, as well as moderate to severe degenerative pathologic changes in dorsal root ganglia and sciatic nerve. In contrast, eribulin mesylate produced no significant deleterious effects on any nerve conduction parameter measured and caused milder, less frequent effects on morphology. Overall, our findings indicate that eribulin mesylate induces less neuropathy in mice than paclitaxel or ixabepilone at equivalent MTD-based doses.

Tato práce je zaměřená na přípravu 1-adamantylmethylmagnesiumbromidu z vhodné a dostupné výchozí látky a průzkum reaktivity připraveného Grignardova činidla. Práce měla dva hlavní body. Jednak přípravu vhodných ketonů s využitím zmíněného Grignardova činidla, a dále průzkum možností zavedení nitroskupiny na připravené ketony elektrofilní aromatickou substitucí., This work is aimed to prepare of 1-adamantylmethylmagnesium bromide from suitable and available precursors and to examine the reactivity of prepared Grignard reagent. Two main branches were explored. At first, the proper ketones were prepared using mentioned Grignard reagent and more, electrophylic aromatic nitrations yielding coresponding nitroketones were examined., Ústav potravinářského inženýrství, obhájeno

In this thesis I have addressed several issues related to the HNL-catalyzed preparation of cyanohydrins. I first demonstrated in Chapter 2 that immobilized HNL as sol-gels and as commercially available Cross Linked Enzyme Aggregates (CLEA®) improved several features of the biocatalyst such as solvent stability, and substrate or product inhibition/deactivation. In particular, MeCLEA was remarkably stable towards the deleterious effect of organic solvent and the enzymatic reaction could be carried out in organic media. The CLEA immobilization strategy is nonetheless enzyme-dependent and I successfully developed the biocatalyst LuCLEA for optimum catalytic performances in organic media as described in Chapter 3. This enantioselective and recyclable biocatalyst appeared to be particularly effective for the preparation of 2-butanone cyanohydrin. In Chapter 4, I used benzaldehyde as a model substrate to develop multistep strategies towards cyanohydrin derivatives based on HNL-CLEA catalysis in organic solvents. The reaction could be carried out in one pot or with limited downstream processing/purification of the cyanohydrin intermediate. In the case of ketones such as acetophenone where unfavourable thermodynamics limit the practical conversion, all attempts to derivatize the cyanohydrin in situ in order to shift the equilibrium were not successful. Cyanohydrins from ketones can indeed be considered as tertiary alcohols which require relatively reactive reagents for derivatization. Under these conditions the biocatalyst was rendered inactive. Since no in situ derivatization method could de designed to enable complete conversion of unreactive ketones, kinetic resolution as a means to produce chiral cyanohydrin was explored in Chapter 5. I established enzymatic activity for a previously unreported ?,?-unsaturated ketone and showed that kinetic resolution was more suitable than the direct synthetic route for the preparation of the corresponding chiral cyanohydrin. As an exte, Biocatalysis and Orgnanic Chemistry, Applied Sciences

Asymmetric hydrogenation of aromatic heterocyclic ketones catalyzed by Cp*Ir(OTf)(Msdpen) (MsDPEN = N-(methanesulfonyl)-1,2-diphenylethylenediamine) affords the heterocyclic alcohols in 93% to > 99% ee. The reaction is conducted in a methanolic solution with a substrate-to-catalyst molar ratio of 200-5000 under 15 atm of H2. The heterocyclic rings of substrates are left intact.

Ultraviolet spectra of thermolysin on mixing with n-alkyl ketones were investigated. Hypochromic effect of UV spectra of enzyme and model compounds was observed. A clear batho-chromic shift (red shift) of thermolysin spectrum was also demonstrated. With increase in chain length of ketones, the red shift was found reduced. The hypochromic and bathochromic effects were significantly suppressed when enzyme or model compounds were pre-treated with inhibitor (phosphor-amidon). There had been no such effect of ketones upon mixing with substrates. It was speculated that ketones interact with the UV sensitive aromatic amino acid residues at the microenvironment of active site of enzyme.

N-Tosyl-(Sa)-binam-L-prolinamide (5 mol%) and benzoic acid (1 mol%) were used as catalysts in the enantioselective direct aldol reaction between different ketones and aldehydes under solvent-free conditions in the presence or absence of water. Under this reaction conditions it was possible to reduce the amount of required ketone to 2 equiv to give the corresponding aldol products with high yields, regio-, diastereo- and enantioselectivities. The aldol reaction between aldehydes or the intramolecular aldol reaction can be also performed with excellent results.

Preparation of azabicyclo-N-oxyls and the electrochemical oxidation of alcohols using them as mediators have been exploited. This oxidation was applicable to a transformation of sterically hindered secondary alcohols into the corresponding ketones in high yields., Tetrahedron Letters, 49(1), pp.48-52; 2008

Fluorination of ketones was achieved by the reaction of silyl enol ethers with iodotoluene difluoride in the presence of BF3·OEt2 and a Et3N·HF complex.

The effects of selected aldehydes, ketones and carboxylic acids on the development of off-flavours in water were studied. Combinations of hexanal, octanal, 2-octanone, 5-nonanone, hexanoic acid and nonanoic acid were rated by the off-flavour intensities they created in water at concentrations just at or below the threshold value of each analyte. Two different sensory panels evaluated the off-flavours induced by different combinations of the analytes. The observations of the two panels agreed well. From these studies, it could be concluded that aldehydes play an important role in the development of off-flavours intensities in water. There were synergistic effects between aldehydes and ketones, as well as between aldehydes and carboxylic acids. Small amounts of aldehydes and carboxylic acids – well below their respective threshold values – caused an increase in the off-flavour intensity. No synergism between ketones and carboxylic acids could be observed

Acetophenone can be used as a fragrance ingredient in soaps, detergents, and perfumes; as a flavoring agent in foods, nonalcoholic beverages, and tobacco; and as a solvent for polymers. Acetophenone is used in perfumery industry, mostly in fragrances like honeysuckle and jasmine, flavors of almond, cherry and strawberry and in tobacco and vanilla works. It is released into the environment from a variety of combustion processes and may be released during its manufacture. Acetophenone has been detected in ambient air and drinking water; exposure of the general public may occur through the inhalation of contaminated air or the consumption of contaminated water. Acute exposure of humans to the vapors of acetophenone may produce skin irritation and transient corneal injury. Acute oral exposure has been observed to cause hypnotic or sedative effects, hematological effects, and a weakened pulse.

High molecular weight poly(phenylene sulfide sulfone) (PPSS) homo- and statistical copolymers have been reproducably synthesized using a known, but complex procedure utilizing 4,4'-dichlorodiphenyl sulfone (DCDPS), sodium hydrosulfide, sodium hydroxide, sodium acetate, and deionized water, in NMP at elevated reaction temperatures and pressure. The effect of these variations, e.g., reaction temperatures and times, molar ratios of H2O-to-NaSH, NMP-to-H2O, etc. were investigated. Optimized conditions were defined, which produced Tg as high as 222°C, very high refractive index (1.70), and tough/solvent resistant films could be prepared by melt fabrication. A two-stage decomposition mechanism in air was demonstrated by dynamic thermal gravimetric analysis. The melt stability of PPSS was improved by incorporating thermally stable endgroups, such as diphenyl sulfone, 4-chlorophenylphenyl sulfone, and t-butylphenoxide. The chemical structures of the endgroups were confirmed by 13C and 1H NMR spectra. Compared with mercaptide endcapped PPSS, the new systems showed higher initial degradation temperatures (2% and 5% weight loss), higher char yield at 650°C in air and a more stable melt viscosity at 300°C. A greatly simplified synthesis of both homo and copolymers has been successfully developed using the new A-A or A-B type thiol-functional monomers, such as bis-(4-mercaptophenyl) sulfone, 4-chloro-4'-mercaptodiphenyl sulfone and 4-chloro-4'-mercapto benzophenone, instead of sodium hydrosulfide. A series of high molecular weight triphenyl phosphine oxide and/or diphenyl ketone containing PPSS copolymers were subsequently synthesized from the bis-(4-mercaptophenyl) sulfone by reaction with 4,4'-dichlorodiphenyl sulfone, bis-(4-fluorophenyl) phenyl phosphine oxide, and 4,4'-difluorobenzophenone in DMAc in the presence of K2CO3 at 160°C. The new phosphine oxide containing PPSS copolymers were completely amorphous, showed improved solubility in common organic solvents and exhibite

The hydrotreatment of various oxygenated groups (ketonic, carboxylic, methoxyphenol) present in bio-oils in the presence of CoMo and NiMo catalysts was studied in a batch reactor using a mixture of model compounds mimicking the real feed. The influence of potential poisons or inhibitors of the reactions (water, ammonia and hydrogen sulfide) was determined. High quantities of water had only a very slight inhibiting effect on the reactions. Ammonia strongly inhibited the conversion of carboxylic esters and the removal of the methoxy group of guaiacol, but, surprisingly, the hydrogenation of the ketonic group was not affected. Hydrogen sulfide depressed the activity of the NiMo catalyst for the conversion of the ketonic group but not that of the CoMo catalyst. It had an enhancing effect on the conversion of the carboxylic ester group and no effect on the removal of the methoxy group of guaiacol. The evolution of activities and selectivities as a function of the concentration of potential inhibitors provided an indication of the catalytic sites responsible for the various reactions. The absence of the influence of ammonia on the hydrogenation of the ketonic group was interpreted as resulting from the participation of nucleophilic sites and hydridic species in the reaction mechanism. Carboxylic esters seem to react on electrophilic sites. Bronsted acids were thought to be responsible for decarboxylation, while uncoordinated metal atoms and sulfhydryl groups could be responsible for the hydrogenation of carboxylic groups. On the other hand, the surface of the alumina support catalyzes the hydrolysis of carboxylic esters into acids. The demethylation of guaiacol occurs for a large part on the Lewis acid-base sites of the gamma-alumina support. The use of hydrogen sulfide and ammonia shows a high potential for controlling the selectivity of reactions occurring in bio-oils hydrotreatment. The present results give hope that the deoxygenation of carboxylic groups could be sele

The elimination of specific oxygenated groups of biomass-derived pyrolysis oils (bio-oils) is necessary for improving their stability. These are mainly unsaturated groups like alkene, carbonyl and carboxylic functions, as well as guaiacyl groups. For practical applications, it is desirable that the reactions are performed selectively in order to avoid excessive hydrogen consumption. The reactions must be done at relatively low temperature in order to limit competitive thermal condensation reactions. In this study, model oxygenated compounds were used, namely 4-methylacetophenone, diethyldecanedioate and guaiacol. They were tested simultaneously in one reaction test in the presence of sulfided cobalt-molybdenum and nickel-molybdenum supported on gamma-alumina catalysts in a batch system. Their reactivity and conversion scheme were determined. The ketonic group is easily and selectively hydrogenated into a methylene group at temperatures higher than 200 degrees C. Carboxylic groups are also hydrogenated to methyl groups, but a parallel decarboxylation occurs at comparable rates. A temperature around 300 degrees C is required for the conversion of carboxylic groups as well as for the conversion of the guaiacyl groups. The main reaction scheme of guaiacol is its transformation in hydroxyphenol which is subsequently converted to phenol. But in batch reactor conditions, guaiacol gives a high proportion of heavy products. CoMo and NiMo catalysts have comparable activities and selectivities. However, the NiMo catalyst has a higher decarboxylating activity than CoMo and also leads to a higher proportion of heavy products during the conversion of guaiacol.

Although microbiological methods of introducing oxygen at C-11 of the steroid molecule are effective, it is obvious that purely synthetic way of producing cortisone and its analogs from bile acids or hecogenin have never been abandoned. Thus, we succeeded to obtain 3alpha-L-acetoxy-11,20-diketo-(5-beta)-pregnane, the key intermediate in the synthesis of 11-oxygenated corticosteroids in a very improved yield exceeding 13% calculated on starting deoxycholic acid by the following sequence of reactions.

In the Mediterranean ecosystem, wildfires are very frequent and the predicted future with a probable increase of fires could drastically modify the vegetation scenarios. Vegetation fires are an important source of gases and primary emissions of fine carbonaceous particles in the atmosphere. In this paper, we present gaseous and particulate emissions data from the combustion of different plant tissues (needles/leaves, branches and needle/leaf litter), obtained from one conifer (Pinus halepensis) and one deciduous broadleaf tree (Quercus pubescens). Both species are commonly found throughout the Mediterranean area, often subject to wildfires. Experiments were carried out in a combustion chamber continuously sampling emissions throughout the different phases of a fire (pre-ignition, flaming and smoldering). We identified and quantified 83 volatile organic compounds including important carcinogens that can affect human health. CO and CO2 were the main gaseous species emitted, benzene and toluene were the dominant aromatic hydrocarbons, methyl-vinyl-ketone and methyl-ethyl-ketone were the most abundant measured oxygenated volatile organic compounds. CO2 and methane emissions peaked during the flaming phase, while the peak of CO emissions occurred during the smoldering phase. Overall, needle/leaf combustion released a greater amount of volatile organic compounds into the atmosphere than the combustion of branches and litter. There were few differences between emissions from the combustion of the two tree species, except for some compounds. The combustion of P. halepensis released a great amount of monoterpenes as α-pinene, β-pinene, p-cymene, sabinene, 3-carene, terpinolene and camphene that are not emitted from the combustion of Q. pubescens. The combustion of branches showed the longest duration of flaming and peak of temperature. Data presented appear crucial for modeling with the intent of understanding the loss of C during different phases of fire and how different t

© 2017 Elsevier LtdThe synthesis of novel 2H-benzimidazole 1,3-dioxides on the basis of o-benzoquinone dioximes interaction with ketones in the presence of acids is described. Nitration of these compounds by nitric acid in acetic acid yields the 5-nitro derivatives of 2H-benzimidazole 1,3-dioxide.

© 2017 Elsevier LtdThe synthesis of novel 2H-benzimidazole 1,3-dioxides on the basis of o-benzoquinone dioximes interaction with ketones in the presence of acids is described. Nitration of these compounds by nitric acid in acetic acid yields the 5-nitro derivatives of 2H-benzimidazole 1,3-dioxide.

Zur Entwicklung und Optimierung leistungsfähiger Katalysatoren werden zahlreiche Versuche durchgeführt, die geplant, dokumentiert und ausgewertet werden müssen. Das im Rahmen dieses interdisziplinären Promotionsvorhabens entwickelte elektronische Dokumentationssystem beschleunigt diese Arbeitsschritte deutlich und hilft, Fehler zu vermeiden. Es wurde im Rahmen mehrerer Forschungsprojekte zu innovativen Decarboxylierenden Kreuzkupplungsreaktionen mit Cu/Pd-Katalysatorsystemen erfolgreich eingesetzt. Die neu entwickelten Eintopfsynthesen eröffnen einen neuen Zugangsweg zu unsymmetrischen Arylketonen und Azomethinen in guten bis sehr guten Ausbeuten. Gegenüber herkömmlichen Decarboxylierungsreaktionen konnte die erforderliche Reaktionstemperatur erheblich abgesenkt werden., The development and optimisation of efficient catalysts is based on numerous experiments, which need to be planned, documented and interpreted. The electronic documentation system developed as part of this PhD thesis significantly accelerates this process and helps to avoid errors. It is used for research on decarboxylative cross-coupling reactions with Cu/Pd catalyst systems. The newly developed one-pot syntheses open a new access to unsymmetric aryl ketones and azomethines in high or very high yields. The reaction temperature could be lowered dramatically compared to similar decarboxylation reactions.