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To explore the potential of the N-cyano sulfilimine group as an amide bond isostere, a derivative of anthranilic diamide was synthesized and evaluated with regard to its physicochemical properties, permeability, and biological activity.

An electron donor–acceptor (EDA) complex is an association between a Lewis base (electron donor) and a Lewis acid (electron acceptor) in the ground state. The EDA complex has received widespread at...

New l-proline-derived bifunctional secondary amine organocatalysts were synthesized for enantioselective Michael reactions in water as a solvent. Application of these catalysts in Michael additions provided high yield (up to 97%) with high stereoselectivity (dr up to 99:1 and ee up to 99%). The effect of phenyl group at (

Highly enantioselective Darzens-type epoxidation of diazoesters with glyoxal derivatives was accomplished using a chiral boron-Lewis acid catalyst, which facilitated asymmetric synthesis of trisubstituted α,β-epoxy esters. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction proceeded in high yield (up to 99 %) with excellent enantio- and diastereoselectivity (up to >99 % ee and >20:1 dr, respectively). The synthetic potential of this method was illustrated by conversion of the products to various compounds such as epoxy γ-butyrolactone, tertiary β-hydroxy ketone and epoxy diester.

The development of a visible light-mediated synthetic method for chiral 1,2-amino tertiary alcohols is described. In the presence of a chiral oxazaborolidinium ion catalyst and photosensitizer, the enantioselective addition of an α-aminoalkyl radical to aryl methyl ketones under visible light provides chiral 1,2-amino tertiary alcohol derivatives in high yields (up to 88%) with excellent enantioselectivities (up to 98% ee). With mechanistic studies such as radical trapping analysis, radical clock analysis, and the measurement of quantum yield, a plausible catalytic cycle is proposed.

Disubstituted 2-pyrones and 2-pyridones were obtained by bifunctional urea-catalyzed Michael addition/lactonization or lactamization followed by a Hg(OAc)2- or Hg(OAc)2/DBU-mediated hydrolysis/decarboxylation/dehydrogenation process. This one-pot two-stage protocol enabled the rapid synthesis of 4,6-disubstituted 2-pyrones and 2-pyridones from dithiomalonate and β,γ-unsaturated α-keto esters in practical yields under mild reaction conditions. Additionally, the obtained 2-pyridones were facilely transformed to 2,4,6-trisubstituted pyridines in excellent yields.

Cervical cancer is the fourth most prevalent cancer among women worldwide and usually develops from cervical intraepithelial neoplasia (CIN). In the present study, we compared alterations in lipids associated with high-grade CIN and cervical cancer with those associated with a normal status and low-grade CIN by performing global lipid profiling on plasma (66 healthy controls and 55 patients with CIN1, 44 with CIN2/3, and 60 with cervical cancer) using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. We identified 246 lipids and found 31 lipids with similar alterations in both high-grade CIN and cervical cancer. Among these 31 lipids, four lipid classes (phosphatidylcholine, phosphatidylethanolamine, diglyceride, and free fatty acids) were identified as the major lipid classes with significant differences in the patients with CIN2/3 and cervical cancer compared to the healthy controls and the patients with CIN1. Lipid metabolites belonging to the same classes were positively correlated with each other. High-grade CIN and cervical cancer induce comparable changes in lipid levels, which are closely related to the development of cervical tumors. These results suggest that lipid profiling is a useful method for monitoring progression to cervical cancer.

Enantioselective 1,2-addition reaction of α-aminoalkyl radical to α,β-unsaturated or aromatic aldehydes to synthesize highly optically active β-amino alcohols has been developed. In the presence of...

To explore how bariatric surgery (BS) modified the obesity-associated gut microbiome, the host metabolome, and their interactions in obese Korean patients.Stool and fasting blood samples were obtained before and 1, 3, 6, and 12 months after BS from 52 patients enrolled in the Korean Obesity Surgical Treatment Study. We analysed the gut microbiome by 16S rRNA gene sequencing and the serum metabolome, including bile acids, by nuclear magnetic resonance spectroscopy and ultrahigh-performance liquid chromatography/triple quadrupole mass spectrometry.Stool metagenomics showed that 27 microbiota were enriched and 14 microbiota were reduced after BS, whereas the abundances and diversity of observed features were increased. The levels of branched-chain amino acids and metabolites of energy metabolism in serum were decreased after surgery, whereas the levels of metabolites related to microbial metabolism, including dimethyl sulphone, glycine, and secondary bile acids, were increased in the serum samples. In addition, we found notable mutual associations among metabolites and gut microbiome changes attributed to BS.Changes in the gut microbiome community and systemic levels of amino acids and sugars were directly derived from anatomical changes in the gastrointestinal tract after BS. We hypothesized that the observed increases in microbiome-related serum metabolites were a result of complex and indirect changes derived from BS. Ethnic-specific environmental or genetic factors could affect Korean-specific postmetabolic modification in obese patients who undergo BS.

In this chapter, recent developments with regard to catalytic enantioselective reactions of furans, derived from biomass such as unsubstituted furan, 2-methylfuran, 2,5-dimethylfuran, and furfural are described. Although several review articles have dealt with the Diels-Alder reactions of furans, there have been no articles highlighting enantioselective versions. The resulting products derived from the catalytic enantioselective reaction of furan are often found as core structures in natural products and pharmaceuticals with important pharmacological activities. After recognizing the valuable skeleton of chiral furan derivatives, numerous attempts have been made to synthesize them by utilizing enantioselective cycloaddition reactions, Friedel-Crafts reactions, and nucleophilic addition reactions. Enantioselective cyclization reactions using furans as the 4π diene component provided chiral dihydrofuran derivatives. On the other hand, Friedel-Crafts and nucleophilic addition reactions served various furan derivatives with a chiral carbon atom in the α-position.

A cyclopropanation/intramolecular rearrangement initiated by the Michael addition of in situ generated ortho-quinone methides (o-QMs) has been developed for the enantioselective synthesis of 2-aryl-2,3-dihydrobenzofurans containing two consecutive stereogenic centers, including a quaternary carbon atom. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction proceeded in excellent yields (up to 95 %) with excellent stereoselectivity (up to >99 ee, up to >20:1 d.r.).

Chiral oxazaborolidinium ion (COBI)-catalyzed enantioselective nucleophilic addition reactions of aldimines using tributyltin cyanide and allyltributylstannane have been developed. Various α-aminonitriles and homoallylic amines were synthesized in high yield (up to 98%) with high to excellent enantioselectivity (up to 99% ee). A rational mechanistic model for the complex of COBI and aldimine is provided to account for these enantioselective reactions.

ConspectusBoron Lewis acid catalysis has a long history and has become one of the most powerful methods for organic synthesis. In addition to achiral boron catalysts such as BX3 (X = F, Cl, Br) and...

An efficient multicomponent dipolar cycloaddition for the synthesis of polycyclic fused pyrrolizidines was developed using N-aromatic zwitterions, aldehydes, and amino acids. The developed reactions proceed through azomethine ylides generated in situ from the decarboxylated reactions of aldehydes and amino acids followed by the [3 + 2] cycloaddition of N-aromatic zwitterions under mild reaction conditions.

Disubstituted 2-pyrones and 2-pyridones were obtained by bifunctional urea-catalyzed Michael addition/lactonization or lactamization followed by a Hg(OAc)

A catalytic enantioselective acyloin rearrangement of acyclic aldehydes to synthesize highly optically active acyloin derivatives is described. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction provided chiral α-hydroxy aryl ketones in high yield (up to 95%) and enantioselectivity (up to 98% ee). In addition, the enantioselective acyloin rearrangement of α,α-dialkyl-α-siloxy aldehydes produced chiral α-siloxy alkyl ketones in high yield (up to 92%) with good enantioselectivity (up to 89% ee).

A Michael addition initiated cyclopropanation/[1,5]-hydrogen shift has been developed for the enantioselective synthesis of Rauhut-Currier products. The reaction of α-alkyl diazoesters and in situ generated o-quinone methides proceeds in the presence of chiral oxazaborolidinium ion, providing Z-stereocontrolled Rauhut-Currier products in high yields (up to 96%) with excellent Z/E selectivities (>20:1) and enantioselectivities (up to >99% ee). The synthetic utility was illustrated by conversion of the product to 3,4-dihydrocoumarins with two adjacent chiral stereocenters.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) affects obese and non-obese individuals. However, mechanisms underlying non-obese non-alcoholic steatohepatitis (NASH) remain unclear. AIMS To attempt to identify metabolic perturbations associated with non-obese and obese NAFLD using a lipidomics approach. METHODS A cross-sectional analysis of 361 subjects with biopsy-proven NAFLD (157 NAFL and 138 NASH) and healthy controls (n = 66) was performed. Individuals were categorised as obese or non-obese based on the Asian cut-off for body mass index. Circulating lipidomic profiling of sera was performed based on the histological severity of NAFLD. Circulating lipidomic alterations were validated with an independent validation set (154 NAFLD subjects [93 NAFL and 61 NASH] and 21 healthy controls). RESULTS Saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in non-obese NAFLD (SM d38:0; P

A highly enantioselective allylation reaction of aldehydes with silyl reagents was developed for the synthesis of a variety of chiral homoallylic alcohols. In the presence of a chiral oxazaborolidinium ion (COBI) catalyst, the reaction proceeded in high yield (up to 99%) with excellent asymmetric induction (up to 99% ee).

Metabolomics is a powerful tool for the investigation of interactions between diet, nutrients, and human metabolism. Ecklonia cava is an edible brown alga that is abundantly found in Korea and Japan and contains unique polyphenols referred to as phlorotannins. However, there are few metabolomics studies related to the effects of polyphenols in humans. In this study, we performed a mass spectrometry-based metabolomics analysis of urine samples from participants with a body mass index (BMI) higher than 25 kg/m2 and lower than 30 kg/m2 to investigate the effects of the intake of seapolynol isolated from E. cava. Metabolomic profiling showed that the levels of riboflavin, urocanic acid, 5-hydroxy-6-methoxyindole glucuronide, and guanidino valeric acid were significantly increased in the seapolynol intake group compared with the placebo group. A correlation analysis was performed to identify the association between the metabolites’ levels and clinical characteristics related to body fat. Among the metabolites whose concentrations changed in the seapolynol intake group, riboflavin was associated with BMI, body weight, fat mass, and percent body fat. These findings suggest that the decreased body fat induced by the intake of seapolynol is related to an increase in the antioxidant effect of riboflavin.

Chiral Lewis acid catalyzed asymmetric formation of cyclobutanones from α-silyloxyacroleins and α-alkyl or α-aryl diazoesters has been developed. In the presence of a chiral oxazaborolidinium ion catalyst, various α-silyloxycyclobutanones possessing a chiral β-quaternary center were synthesized in high yield (up to 91%) with excellent enantio- and diastereoselectivity (up to 98% ee and up to >20:1 dr) through tandem cyclopropanation/semipinacol rearrangement. The synthetic potential of this method was illustrated by conversion of the product to various cyclic compounds such as γ-lactone, cyclobutanol, and cyclopentanone.

Age-related osteoporosis is characterized by reduced bone mineralization and reduced bone strength, which increases the risk of fractures. We examined metabolic changes associated with age-related bone loss by profiling lipids and polar metabolites in tibia and femur bone tissues from young (5 months old) and old (28 months old) male C57BL/6J mice using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Partial least-squares discriminant analysis showed clear differences in metabolite levels in bone tissues of young and old mice. We identified 93 lipid species, including free fatty acids, sphingolipids, phospholipids, and glycerolipids, that were significantly altered in bone tissues of old mice. In addition, the expression of 26 polar metabolites differed significantly in bone tissues of old mice and young mice. Specifically, uremic toxin metabolite levels (p-cresyl sulfate, hippuric acid, and indoxylsulfate) were higher in bone tissues of old mice than in young mice. The increase in p-cresyl sulfate, hippuric acid, and indoxylsulfate levels were determined using targeted analysis of plasma polar extracts to determine whether these metabolites could serve as potential osteoporosis biomarkers. This study demonstrates that LC-MS-based global profiling of lipid and polar metabolites can elucidate metabolic changes that occur during age-related bone loss and identify potential biomarkers of osteoporosis.

Atherosclerosis is a chronic inflammatory disease characterized by thickening of the arterial wall. However, a limited number of studies have been conducted on metabolic profiling of human aortic tissue.We applied liquid chromatography/mass spectrometry to perform global and targeted profiling of plaque-containing aortic tissue. The aorta samples included plaque-containing (n = 18) and control plaque-free (n = 24) aortic tissue from patients undergoing aortic surgery.The metabolic patterns of atherosclerotic and control vessels were significantly different. Metabolites in the purine and glutathione pathways showed dysregulation of oxidative stress in plaques, and levels of glucosylceramide, tryptophan, and kynurenine, which are related to inflammation, were also altered. Interestingly, an increased level of quinic acid was observed in plaques (p 0.000), and we demonstrated an inhibitory effect of quinic acid on inflammatory activation and oxidative stress in macrophages.Our study provides insight into the disease mechanism and potential markers of atherosclerosis through comprehensive metabolic profiling of human aortic tissue samples containing plaque.

Herein, we demonstrate a new catalytic cycloaddition of quinolinium zwitterions involving a gold-bound allylic cation intermediate. This ligand-free higher-order cycloaddition efficiently affords a variety of fused 1,4-diazepine derivatives in a stereospecific manner at room temperature.

Green tea (GT) is a widely consumed beverage with health benefits, including antiobesity effects; however, the efficacy of GT on lipid levels associated with obesity is not clearly understood. Here, we examined the impact of GT consumption on lipid metabolism in the livers of high-fat diet (HFD)-induced obese mice. We performed lipid profiling using ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry in C57BL/6J mice fed a normal diet (ND), HFD and HFD with GT for 12 weeks. The partial least squares discriminant analysis score plot showed a difference among the groups and revealed that the levels of several lipid metabolites were altered in mice fed HFD with GT. The decreased levels of lysophospholipids (LPLs), such as lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine, in HFD mice compared to those of the ND group were recovered by supplementation of GT. In agreement with these lipid metabolites changes, hepatic lysophosphatidylcholine acyltransferase 2/4 was significantly increased in HFD mice. This study showed abnormal changes in lipid species associated with obesity, and these levels were attenuated by GT intake, suggesting a relationship between the reduction of hepatic LPL levels and inflammation in obesity.

A highly enantioselective hydrosilylation of ketones was developed for the synthesis of a variety of chiral secondary alcohols. In the presence of a chiral oxazaborolidinium ion (COBI) catalyst, the reaction proceeded with good yields (up to 99%) with excellent enantioselectivities (up to 99% ee).

Atherosclerosis is a leading cause of cardiovascular disease (CVD), but the effect of diet on the atherosclerotic heart’s metabolism is unclear. We used an integrated metabolomics and lipidomics approach to evaluate metabolic perturbations in heart and serum from mice fed an atherogenic diet (AD) for 8, 16, and 25 weeks. Nuclear magnetic resonance (NMR)-based metabolomics revealed significant changes in sulfur amino acid (SAA) and lipid metabolism in heart from AD mice compared with heart from normal diet mice. Higher SAA levels in AD mice were quantitatively verified using liquid chromatography-mass spectrometry (LC/MS). Lipidomic profiling revealed that fatty acid and triglyceride (TG) levels in the AD group were altered depending on the degree of unsaturation. Additionally, levels of SCD1, SREBP-1, and PPARγ were reduced in AD mice after 25 weeks, while levels of reactive oxygen species were elevated. The results suggest that a long-term AD leads to SAA metabolism dysregulation and increased oxidative stress in the heart, causing SCD1 activity suppression and accumulation of toxic TGs with a low degree of unsaturation. These findings demonstrate that the SAA metabolic pathway is a promising therapeutic target for CVD treatment and that metabolomics can be used to investigate the metabolic signature of atherosclerosis.

To reduce solar heat and glare from visible light, the color of window panes need to be controlled by electronic energy. Metal oxides deposited on these “smart” windows such as WO 3 , Nb 2 O 5 , and NiO can change the color of the glass by absorbing visible rays. It is important to control the chemical and physical characteristics of the surface of films and to apply a uniformly thin film to obtain a superior product. In this study, we generated templates as nanostructured WO 3 monolayers in nanorods with 400 nm-sized polystyrene (PS) beads. Honeycomb structures were prepared from the well-ordered monolayer template with PS beads that were synthesized by wet chemistry. We investigated the enhanced electrochromic (EC) properties of a honeycomb structured WO 3 thin films which were composed of WO 3 nanostructures. Nanoarchitectural properties like morphology of films, crystalline phases and the structures of WO 3 nanoparticles were examined by Field Emission Scanning Electron Microscopy, X-ray diffraction and Transmission Electron Microscopy. And EC standards such as the variation of transmittance, reaction time and efficiency of redox reactions called by “coloration efficiency” were measured by UV–Vis spectrophotometer, and cyclic voltammetry. The electrochromic reaction rate of honeycomb structured WO 3 thin films was fast (coloration time: 5.86 s and bleaching time: 6.65 s) but, the variation of light transmission (Δ85.04% at 700 nm wavelength) was comparable to that of flat WO 3 film with the similar thickness of about 300 nm. These results suggested that the surface area enlarged by the honeycomb structure induced by PS templating caused the simultaneous redox reaction in the entire WO 3 film.

A Michael addition initiated cyclopropanation/retro-Claisen rearrangement tandem reaction was developed for the enantioselective synthesis of highly functionalized 2,5-dihydrooxepines. In the presence of a chiral oxazaborolidinium ion (COBI) catalyst, the reaction proceeds to give good yields and high enantioselectivity.

A new chiral Brønsted acid derived from carboxylic acid and a chiral oxazaborolidinium ion (COBI), as an activator, is introduced. This acid was successfully applied as a catalyst for the highly enantioselective protonation/nucleophilic addition of diazoesters with carboxylic acids.

Background Myocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear. Methods We evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1h, 1day and 10day after coronary ligation, using global profiling based on metabolomics. Results A time-dependent increase or decrease in polar and lipid metabolite levels was measured. The S-adenosylmethionine (SAM) concentration and the SAM/S-adenosylhomocysteine (SAH) ratio gradually decreased in a time-dependent manner and were significantly downregulated 10days after MI. Transcriptome analysis revealed that the levels of coenzyme Q ( Coq )- 3 and Coq5 , both of which are SAM-dependent methyltransferases, were decreased in the MI groups. These results suggested that dysregulation of SAM may be related to down regulated COQ biosynthetic pathway. In addition, short-chain (C3) and medium-chain (C4–C12) acylcarnitine levels gradually decreased, whereas long-chain acylcarnitine (C14–18) levels increased, owing to a defect in β-oxidation during ischemia. These changes are related to energy-dependent metabolic pathways, and a subsequent decrease in adenosine triphosphate concentration was observed. Conclusions The comprehensive integration of various omics data provides a novel means of understanding the underlying pathophysiological mechanisms of MI.

An asymmetric Michael addition of 2-oxochroman-3-carboxylate esters to trans-β-nitroolefins is described. This strategy can give direct access to dihydrocoumarin derivatives bearing adjacent quaternary and tertiary stereocenters with up to >99% yield, >20:1 dr, and >99% ee. The adduct was further transformed to a spiro-dihydrocoumarin compound in three steps with good yield.

Background The renal dysfunction of chronic kidney disease (CKD) alters serum metabolite levels, but it is not clear how diabetes mellitus (DM) affects the metabolic changes in CKD. Methods Serum metabolites from pre-dialysis CKD patients ( n = 291) with or without DM and from healthy controls ( n = 56) was measured using nuclear magnetic resonance. Results Initial principal components analysis and partial least squares-discriminant analysis score plots segregated the CKD patients according to CKD stage and separated DM from non-DM patients. In the CKD patients, associations were seen with clinical characteristics, hyperglycemia, altered amino acid metabolism, accumulated uremic toxins, and dyslipidemia. Of interest, diabetes more strongly affected the metabolic signature during early stage CKD. Furthermore, serum metabolite profiles were successfully applied to the PLS regression model to predict the estimated glomerular filtration rate. The R 2 values from the PLS models for CKD patients with DM were higher than those for CKD without DM. Conclusions Metabolomics is useful clinically for providing a metabolic signature that is associated with the CKD phenotype and diabetes more seriously affects patients with early stage CKD compared to those with advanced CKD.

New indoline dyes (RK-1–4) were designed with a planar geometry and high molar extinction coefficient, which provided surprising power conversion efficiency (PCE) with a thin titanium dioxide film in dye-sensitized solar cells (DSCs). They had a difference in only alkyl chain length. Despite the same molecular structure, the performance of the respective DSCs varied significantly. Investigating the dye adsorption processes and charge transfer kinetics, the alkyl chain length was determined to affect the dye surface coverage as well as the recombination between the injected photoelectrons and the oxidized redox mediators. When applied to the DSCs as a light harvester, RK-3 with the dodecyl group exhibited the best photocurrent density, consequently achieving the best PCE of 9.1% with a 1.8 μm active and 2.5 μm scattering layer because of the most favorable charge injection. However, when increasing the active layer thickness, overall device performance deteriorated and the charge collection and regeneration played major roles for determining the PCE. Therefore, RK-2 featuring the highest surface coverage and moderate alkyl chain length obtained the highest PCEs of 8.8% and 7.9% with 3.5 and 5.1 μm active layers, respectively. These results present a promising perspective of organic dye design for thin film DSCs.