Green organic solvents such as lactate esters have broad industrial applications and favorable environmental profiles. Thus, manufacturing and use of these biodegradable solvents from renewable feedstocks help benefit the environment. However, to date, the direct microbial biosynthesis of lactate esters from fermentable sugars has not yet been demonstrated.

3-Monochloropropane-1,2-diol (3-MCPD) esters and glycidyl esters (GE) are heat-induced contaminants which form during oil refining process, particularly at the high temperature deodorization stage. It is worth to investigate the content of 3-MCPD and GE in fries which also involved high temperature. The content of 3-MCPD esters and GE were monitored in fries. The factors that been chosen were temperature and duration of frying, and different concentration of salt (NaCl). The results in our study showed that the effect was in the order of concentration of sodium chloride < frying duration < frying temperature. The content of 3-MCPD esters was significantly increased whereas GE was significantly decreased, when prolong the frying duration. A high temperature results in a high 3-MCPD ester level but a low GE level in fries. The present of salt had contributed significant influence to the generation of 3-MCPD. The soaking of potato chips in salt showed no significant effect on the level of GE during the frying. The oil oxidation tests showed that all the fries were below the safety limit. Hence, the frying cycle, temperature and the added salt to carbohydrate-based food during frying should be monitored.

A novel, metal-free aerobic oxidation method is described. 4-Dimethylaminopyridine (DMAP) successfully catalyzed the oxidation of aryl α-halo esters to corresponding aryl α-keto esters (up to 95% yield) under mild reaction conditions (Li2CO3, dimethylacetamide, air, and room temperature). A mechanism has been proposed where the oxidation proceeds through a [3 + 2] cycloaddition between O2 in an air atmosphere and pyridinium ylides. The ylides are supposedly generated from aryl α-halo esters and DMAP in the presence of carbonates. Based on the plausible mechanism, the potential of DMAP as a catalyst in oxidation reactions was extended.

Galantamine hydrobromide (GAL) is a reversible acetylcholinesterase inhibitor, with properties to increase the concentration of acetylcholine in several brain structures. The aim of this study is to determine the effect of new galantamine peptide esters: 3,4-dichlorophenyl-alanil-leucil-glycine-galantamine (GAL-LEU) and 3,4-dichlorophenyl-alanil-valil-glycine-galantamine (GAL-VAL), on locomotor activity in mice and cognitive processes in experimental model of learning and memory in rats. The results showed that per oral administration of GAL-LEU in a dose of 3 mg per kg improved the cognitive processes by increasing the conditional avoidances and learning ability after the 5th day of application and preserved the memory at the 12th day of the study.

Valerenic acid (VA) is a β2/3 subunit-specific modulator of γ-aminobutyric acid (GABA) type A (GABAA) receptors inducing anxiolysis. Here we analyze if VA-esters can serve as prodrugs and if different ester structures have different in vitro/in vivo effects. Modulation of GABAA receptors expressed in Xenopus oocytes was studied with 2-microelectrode-voltage-clamp. Anxiolytic effects of the VA-esters were studied on male C57BL/6N mice by means of the elevated plus maze-test; anticonvulsant properties were deduced from changes in seizure threshold upon pentylenetetrazole infusion. VA was detected in plasma confirming hydrolysis of the esters and release of VA in vivo. Esterification significantly reduced the positive allosteric modulation of GABAA (α1β3γ2S) receptors in vitro. in vivo, the studied VA-ester derivatives induced similar or even stronger anxiolytic and anticonvulsant action than VA. While methylation and propylation of VA resulted in faster onset of anxiolysis, the action of VA-ethylester was longer lasting, but occurred with a significant delay. The later finding is in line with the longer lasting anticonvulsant effects of this compound. The estimated VA plasma concentrations provided first insight into the release kinetics from different VA-esters. This might be an important step for its future clinical application as a potential non-sedative anxiolytic and anticonvulsant.

Organophosphate esters (OPEs) and phthalic acid esters (PAEs) are widespread contaminants in the environment. The variations of these chemicals in plants throughout their life cycle is little known. In this study, OPEs, OPE metabolites, and PAEs in peanut and corn grown under field conditions, soil, and air were measured to understand the uptake and translocation, distributions in the plant compartments, and metabolism in the plants. The soil concentrations showed an enrichment effect of OPEs onto the rhizosphere soil but a depletion effect of PAEs on rhizosphere soils. The PAE concentrations between peanut (with a mean of 1295 ng/g dw) and corn (3339 ng/g dw) were significantly different, but the OPE concentrations were not significantly different (with means of 15.6 and 19.2 ng/g dw, respectively). OPE metabolites were also detected in the plants, with lower concentrations and detection rates. Similarities and differences in the temporal variations of the concentrations of traditional OPEs, novel OPEs, and PAEs in plants during their growth were observed. The variations were dependent on both plant species and particular tissues. The leaf compartment is the most important reservoir of OPEs and PAEs (but not OPE metabolites) for both species, highlighting the importance of an aerial uptake pathway. The chemicals have a low potential to be translocated into peanut and corn kernels, reducing their risks via food consumption. Less hydrophobic compounds have higher root concentration factors in this study. These observations differ from those of previous hydroponic experiments.

Chiral cyclopropanols are highly desirable building blocks for medicinal chemistry, but the stereoselective synthesis of these molecules remains challenging. Here, a novel strategy is reported for the diastereo- and enantioselective synthesis of cyclopropanol derivatives via the biocatalytic asymmetric cyclopropanation of vinyl esters with ethyl diazoacetate (EDA). A dehaloperoxidase enzyme from Amphitrite ornata was repurposed to catalyze this challenging cyclopropanation reaction, and its activity and stereoselectivity were optimized via protein engineering. Using this system, a broad range of electron-deficient vinyl esters were efficiently converted to the desired cyclopropanation products with up to 99.5:0.5 diastereomeric and enantiomeric ratios. In addition, the engineered dehaloperoxidase-based biocatalyst is able to catalyze a variety of other abiological carbene transfer reactions, including N-H/S-H carbene insertion with EDA as well as cyclopropanation with diazoacetonitrile, thus adding to the multifunctionality of this enzyme and defining it as a valuable new scaffold for the development of novel carbene transferases.

The low thermoplasticities of polysaccharide esters make them unsuitable for melt spinning. In this study, we aimed to overcome this problem by mixed esterification of paramylon, a euglenoid β-1,3-glucan with short- and medium-chain acyl groups, as melt-spinnable materials. Thermal analyses revealed that all the synthesized paramylon mixed esters exhibited glass transition temperatures greater than 100 °C; some of them showed large differences between the melting and 5%-weight-loss temperatures (Td5s) and are extrudable through a spinneret at a temperature ~100 °C below Td5, rendering them potential candidates for the production of melt-spun filaments. Among the various compounds investigated, paramylon acetate propionates, in which the degrees of acetyl- and propionyl-group substitution were 0.5-0.7 and 2.2-2.5, respectively, could be melt-spun to yield mechanically tough crystalline monofilaments. In contrast, the melt spinning of cellulose acetate propionate, analogous to the paramylon acetate propionates in terms of acyl substituents, their substitution degrees, and molecular weights, but differs from it in terms of the glucose linkage mode (i.e., β-1,3 vs β-1,4), yielded brittle, charred, and short filaments. Curdlan acetate propionate, another analogue with a degree of polymerization five times larger than that of paramylon mixed esters, was not extrudable due to the lack of thermoplasticity. Therefore, we herein confirmed the superiority of paramylon as a primary raw material for melt-spun filaments.

The aza-Michael addition of 1,2,3,6-tetrahydrophthalimide with symmetrical fumaric esters has been performed efficiently in a solvent-free system at 100 °C and using 1,4-diazabicyclo[2.2.2]octane (DABCO) as a base in the presence of tetrabutylammonium bromide (TBAB). The products were obtained in good to high yields within 2.5-7.0 h. This reaction worked well on linear alkyl fumarates and was not effective with nonlinear alkyl fumarates. Although the reaction was also applicable to acrylates such as n-butyl acrylate, methacrylates and crotonates were not suitable Michael acceptors for this reaction.

To test the hypothesis that dimethyl fumarate (DMF, Tecfidera) elicits different biological changes from DMF combined with monoethyl fumarate (MEF) (Fumaderm, a psoriasis therapy), we investigated DMF and MEF in rodents and cynomolgus monkeys. Possible translatability of findings was explored with lymphocyte counts from a retrospective cohort of patients with MS.

Diazo compounds are versatile reagents in chemical synthesis and biology due to the tunable reactivity of the diazo functionality and its compatibility with living systems. Much effort has been made in recent years to explore their accessibility and synthetic potential; however, their preparation through stereoselective enzymatic asymmetric synthesis has been scarcely reported in the literature. Alcohol dehydrogenases (ADHs, also called ketoreductases, KREDs) are powerful redox enzymes able to reduce carbonyl compounds in a highly stereoselective manner. Herein, we have developed the synthesis and subsequent bioreduction of nine α-diazo-β-keto esters to give optically active α-diazo-β-hydroxy esters with potential applications as chiral building blocks in chemical synthesis. Therefore, the syntheses of prochiral α-diazo-β-keto esters bearing different substitution patterns at the adjacent position of the ketone group (N3CH2, ClCH2, BrCH2, CH3OCH2, NCSCH2, CH3, and Ph) and in the alkoxy portion of the ester functionality (Me, Et, and Bn), were carried out through the diazo transfer reaction to the corresponding β-keto esters in good to excellent yields (81-96%). After performing the chemical reduction of α-diazo-β-keto esters with sodium borohydride and developing robust analytical conditions to monitor the biotransformations, their bioreductions were exhaustively studied using in-house made Escherichia coli overexpressed and commercially available KREDs. Remarkably, the corresponding α-diazo-β-hydroxy esters were obtained in moderate to excellent conversions (60 to >99%) and high selectivities (85 to >99% ee) after 24 h at 30 °C. The best biotransformations in terms of conversion and enantiomeric excess were successfully scaled up to give the expected chiral alcohols with almost the same activity and selectivity values observed in the enzyme screening experiments.

Issues on 3-monochloropropane-diol-1,2-diol (MCPD) esters and glycidyl esters in refined oil have gained much attention when these heat-induced contaminants are associated with health implications. Oil that undergoes the frying process could influence the fates of 3-MCPD esters and glycidyl esters, especially with the addition of an anti-clouding agent. In this study, we investigated the effect of polyglycerol fatty acid esters (PGE) on the transients of 3-MCPD esters and glycidyl esters in palm olein (POo) during intermittent frying. Thermal resistance of POo fortified with PGE (0.1% to 0.4%) was assessed for 8 h of daily frying operations at 180 °C across five consecutive days. The addition of PGE decelerated the reduction of 3-MCPD esters and glycidyl esters with the progression of frying. The presence of these compounds coincided with the amount of oil taken up by the fried product. The inclusion of PGE in POo also induced higher augmentation of polar compound fractions, i.e., oxidised triacylglycerols (OxTAG) and polymerised triacylglycerols (PTAG), but gave comparable free fatty acid (FFA), p-anisidine value (AnV), total chloride and fatty acid composition (FAC) with control oil (POo). The results also showed that the presence of chloride in POo did not onset further formation of 3-MCPD esters and glycidyl esters throughout the frying period. As the behaviours of 3-MCPD esters and glycidyl esters were affected by PGE, only a sufficient amount should be added into POo to ensure oil clarity at a realistic period.

Fumaric acid esters (FAE) are small molecules with immunomodulating, anti-inflammatory, and anti-oxidative effects. FAE were introduced as a systemic psoriasis treatment in 1959 and empirically developed further between 1970 and 1990 in Germany, Switzerland, and the Netherlands. The development of FAE as psoriasis treatment did not follow the traditional drug development phases. Nonetheless, in 1994 FAE were approved in Germany for the treatment of severe plaque psoriasis. FAE are currently one of the most commonly used treatments in Germany, and FAE are increasingly being used as an unlicensed treatment in several other European countries. To date, six randomized controlled trials and 29 observational studies have evaluated FAE in a combined total of 3,439 patients. The efficacy and safety profile of FAE is favorable. About 50%-70% of patients achieve at least 75% improvement in psoriasis severity after 16 weeks of treatment. Common adverse events of FAE include gastrointestinal complaints and flushing symptoms, which lead to treatment discontinuation in up to 40% of patients. Lymphocytopenia, eosinophilia, and proteinuria are commonly observed during FAE treatment, but rarely require treatment discontinuation. The long-term safety profile of continuous FAE treatment is favorable without an increased risk for infections, malignancies, or other serious adverse events. There are no known drug-interactions for FAE. The 2009 European evidence-based S3-guidelines on psoriasis treatment recommend FAE and suggest it as a first-line systemic treatment for moderate-to-severe plaque psoriasis. This review is aimed to give an overview of FAE treatment in the management of psoriasis.

Measures of behavioral sensitivity provide an important guide for choosing the stimulus concentrations used in functional experiments. This information is particularly valuable in the olfactory system as the neural representation of an odorant changes with concentration. This study focuses on acetate esters because they are commonly used to survey neural activity in a variety of olfactory regions, probe the behavioral limits of odor discrimination, and assess odor structure-activity relationships in mice. Despite their frequent use, the relative sensitivity of these odorants in mice is not available. Thus, we assayed the ability of C57BL/6J mice to detect seven different acetates (propyl acetate, butyl acetate, pentyl acetate, hexyl acetate, octyl acetate, isobutyl acetate, and isoamyl acetate) using a head-fixed Go/No-Go operant conditioning assay combined with highly reproducible stimulus delivery. To aid in the accessibility and applicability of our data, we have estimated the vapor-phase concentrations of these odorants in five different solvents using a photoionization detector-based approach. The resulting liquid-/vapor-phase equilibrium equations successfully corrected for behavioral sensitivity differences observed in animals tested with the same odorant in different solvents. We found that mice are most sensitive to isobutyl acetate and least sensitive to propyl acetate. These updated measures of sensitivity will hopefully guide experimenters in choosing appropriate stimulus concentrations for experiments using these odorants.

To study the chemical constituents of the EtOAc extract of Armillaria gallica 012m.

Hyperammonemia is a frequent finding in various organic acidemias. One possible mechanism involves the inhibition of the enzyme N-acetylglutamate synthase (NAGS), by short-chain acyl-CoAs which accumulate due to defective catabolism of amino acids and/or fatty acids in the cell. The aim of this study was to investigate the effect of various acyl-CoAs on the activity of NAGS in conjunction with the formation of glutamate esters. NAGS activity was measured in vitro using a sensitive enzyme assay with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) product analysis. Propionyl-CoA and butyryl-CoA proved to be the most powerful inhibitors of N-acetylglutamate (NAG) formation. Branched-chain amino acid related CoAs (isovaleryl-CoA, 3-methylcrotonyl-CoA, isobutyryl-CoA) showed less pronounced inhibition of NAGS whereas the dicarboxylic short-chain acyl-CoAs (methylmalonyl-CoA, succinyl-CoA, glutaryl-CoA) had the least inhibitory effect. Subsequent work showed that the most powerful inhibitors also proved to be the best substrates in the formation of N-acylglutamates. Furthermore, we identified N-isovalerylglutamate, N-3-methylcrotonylglutamate and N-isobutyrylglutamate (the latter two in trace amounts), in the urines of patients with different organic acidemias. Collectively, these findings explain one of the contributing factors to secondary hyperammonemia, which lead to the reduced in vivo flux through the urea cycle in organic acidemias and result in the inadequate elimination of ammonia.

Long chain cellulose esters are internally plasticized bio-based materials, which have good future potential in several applications such as coatings, films and plastics. The long chain cellulose esters with different side chain lengths were synthesized using different esterification methods. When homogeneous esterification was used, the acyl chloride method was the most effective esterification method and cellulose esters prepared using this method have the highest degree of substitution values (DS). In this case, the long chain cellulose esters showed DS values from 0.3 to 1.3 depending on the side chain length of cellulose esters. CDI activation, vinyl transesterification and anhydride routes resulted in somewhat lower DS values. The cellulose was also pretreated with ozone, which decreased cellulose molar mass, and resulted in synthesized cellulose esters having higher DS and better reaction efficiency than untreated cellulose. When heterogeneous esterifications were used, only acyl chloride method seemed to work.

Three new multiflorane-type triterpene esters, i.e. 7α-hydroxymultiflor-8-ene-3α,29-diol 3-acetate-29-benzoate (1), 7α-methoxymultiflor-8-ene-3α,29-diol 3,29-dibenzoate (2), and 7β-methoxymultiflor-8-ene-3α,29-diol 3,29-dibenzoate (3), were isolated from seeds of Cucurbita maxima, along with the known compound, multiflora-7,9(11)-diene-3α,29-diol 3,29-dibenzoate (4). Compound 1 exhibited melanogenesis inhibitory activities comparable with those of arbutin. In cytotoxicity assays, compounds 1 and 3 exhibited weak cytotoxicity, with IC50 values of 34.5-93.7 μM against HL-60 and P388 cells.

Amidation is an important reaction for bioderived platform molecules, which can be upgraded for use in applications such as polymers. However, fundamental understanding of the reaction especially in the presence of multiple groups is still lacking. In this study, the amidation of dimethyl fumarate, maleate, and succinate through ester ammonolysis was examined. The reaction networks and significant side reactions, such as conjugate addition and ring closing, were determined. A preliminary kinetic comparison among additional C4 and C6 esters showed a significant correlation between molecular structure and ammonolysis reactivity. Esters with a C=C double bond in the molecule backbone were found to have higher ammonolysis reactivity. To improve the selectivity to unsaturated amides rather than byproducts, the effects of thermal conditions and additives in dimethyl fumarate ammonolysis were examined. Lower temperature and decreasing methoxide ion concentration in the solution relative to the base case conditions increased the fumaramide selectivity from 67.1 to 90.6%.

Several efficient synthetic routes giving readily access to (oxy)-sitosterol esters and (oxy)-cholesterol esters derived respectively from oleic acid and from 9,10-dihydroxystearic acid were developed for the first time. This approach allowed that sufficient amounts of the latter were available in order to carry out further biological studies.