l-Proline-derived chiral bifunctional (thio)urea organocatalysts epi-PTU and epi-PU were newly synthesized, and their catalytic performances were compared with their C6 epimeric catalysts PTU and PU in various Michael reactions of nitrostyrene in terms of reactivities and stereoselectivities. The experimental results indicate that a proper relative stereochemistry at C2 and C6 in l-proline-derived bifunctional organocatalysts is important for successful catalysis and that catalysts (PTU and PU) with the 2S,6R configuration are much more efficient.

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).

The planarity of an organic sensitizer is one of the most crucial factors for determining molar absorptivity and intramolecular charge transfer (ICT). The photovoltaic performance of dye-sensitized solar cells dramatically changed depending on the planarity of the donor, although all dyes exhibited similar extinction coefficients, electrochemical characteristics, as well as the amount of loaded dye. The power conversion efficiency (PCE) of planar donor dyes was 3 times greater than that of twisted donor dyes because of more rapid ICT. In addition, RK-3 dye, characterized by additional donor groups on an indoline unit, exhibited broad light-harvesting ability with higher performance as compared to those observed for planar dyes with a single donor attached to the thin-film photoanode (1.8 μm transparent + 2.5 μm scattering film). The champion cell of RK-3 exhibited a PCE of 10.3% when the thickness of the active film increased to 3.5 μm, as well as when an antireflection layer was applied with an iodine-based electrolyte.

BackgroundMyocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear.MethodsWe evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1 h, 1 day and 10 day after coronary ligation, using global profiling based on metabolomics.ResultsA 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 10 days 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.ConclusionsThe comprehensive integration of various omics data provides a novel means of understanding the underlying pathophysiological mechanisms of MI.

AbstractA 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.

Cyclopropane mit Formyl- und Vinylsubstituenten werden unter Freisetzung der Winkelspannung über einen Boot-förmigen Übergangszustand in 2,5-Dihydrooxepine umgewandelt. D. H. Ryu und Mitarbeiter zeigen in ihrer Zuschrift auf S. 8789 ff., dass eine katalytische Tandemreaktion aus Cyclopropanierung und Retro-Claisen-Umlagerung in Gegenwart eines chiralen Oxazaborolidiniumkatalysators in einem einzigen Schritt hoch funktionalisierte 2,5-Dihydrooxepine mit exzellenter Enantioselektivität liefert.

AbstractA 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.

Cyclopropanes possessing formyl and vinyl groups are converted into 2,5-dihydrooxepines with release of the angle strain through a boat-like transition state. In their Communication on page 8663 ff., D. H. Ryu and co-workers show that a catalytic tandem cyclopropanation/retro-Claisen rearrangement reaction in the presence of a chiral oxazaborolidinium ion catalyst gives highly functionalized 2,5-dihydrooxepines in a single step with excellent enantioselectivity.

Chiral oxazaborolidinium ion-catalyzed asymmetric cyclopropanation of α- or α,β-substituted acroleins with α-alkyl-α-diazoesters has been developed. With this methodology, chiral functionalized cyclopropanes containing a quaternary stereogenic center were obtained with high to excellent enantioselectivities (up to >99% ee). The synthetic utility of optically enriched functionalized cyclopropane was demonstrated in the first total synthesis of (+)-hamavellone B, which establishes the absolute configuration of natural (+)-hamavellone B.

A series of novel l-proline derived tertiary amine bifunctional organocatalysts 9 are reported, which were applied to the asymmetric Michael addition of dithiomalonates 2 to trans-β-nitroolefins 1. The reaction proceeded in high yields (up to 99%) with high enantioselectivities (up to 97% ee). The synthetic utility of this methodology was demonstrated in the short synthesis of (R)-phenibut in high yield.

A convenient one-pot procedure to synthesize a variety of highly optically active syn-α-aryl-β-hydroxy Weinreb amides using an asymmetric Roskamp/reduction strategy is described. An oxazaborolidinium ion catalyzed asymmetric Roskamp reaction of α-aryl diazo Weinreb amides with aldehydes produced α-phenyl-β-keto Weinreb amides, which were in situ reduced with zinc borohydride to give syn-α-aryl-β-hydroxy Weinreb amides in good yields (up to 87%) with high enantioselectivities (up to 99% ee) and syn stereoselectivities (>20:1).

A novel, catalytic enantioselective route to synthesize a variety of α-tertiary aryl ketones via a boron Lewis acid promoted formal insertion of aryldiazoalkane into the C–H bond of both aromatic and aliphatic aldehydes is described. In the presence of chiral (S)-oxazaborolidinium ion catalyst 1, the reaction proceeded in good yields (up to 94%) with excellent enantioselectivities (up to 99% ee).

Highly enantioselective 1,3-dipolar cycloaddition reactions of α-substituted diazoacetates are accomplished by catalysis of the chiral oxazaborolidinium ion. Functionalized 2-pyrazolines are synthesized in high to excellent enantiomeric ratios (up to >99:1). The synthetic utility of 2-pyrazoline was expanded via preparation of 2,4-diamino ester compounds bearing a chiral quaternary carbon center.

•We applied metabolic profiling in serum of patients with myocardial infarction (MI).•Gender-specific metabolic patterns in serum of patients with MI were identified.•LC–MS based profiling and various statistical analysis were used in this study.•Metabolomics can be used to clarify the mechanism underlying MI and gender difference.Myocardial infarction (MI), a leading cause of death worldwide, results from prolonged myocardial ischemia with necrosis of myocytes due to a blood supply obstruction to an area of the heart. Many studies have reported gender-related differences in the clinical features of MI, but the reasons for these differences remain unclear. In this study, we applied ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) and various statistical methods—such as multivariate, pathway, and correlation analyses—to identify gender-specific metabolic patterns in polar metabolites in serum from healthy individuals and patients with MI. Patients with diagnosed MI (n = 68), and age- and body mass index-matched healthy individuals (n = 68), were included in this study. The partial least-squares discriminant analysis (PLS-DA) model was generated from metabolic profiling data, and the score plots showed a significant gender-related difference in patients with MI. Many pathways were associated with amino acids and purines; amino acids, acylcarnitines, and purines differed significantly between male and female patients with MI. This approach could be utilized to observe gender-specific metabolic pattern differences between healthy controls and patients with MI.

Highly stereoselective (Z)-silyl enol ethers were prepared from alkyl aryl ketones and trimethylsilyldiazomethane (TMSD) using an oxazaborolidinium ion catalyst. In addition, ring-expanded silyl enol ethers were successfully constructed from cyclic ketones. Their synthetic utilities were shown by sequential Mukaiyama aldol and [2 + 2]-cycloaddition reactions.

Chiral oxazaborolidinium ion-catalyzed Csp2–H functionalization of enones using diazoacetate has been developed. Various β-substituted cyclic enones were synthesized in high yield (up to 99%) with high to excellent enantioselectivity (up to 99% ee). The synthetic utility of this reaction was demonstrated by the formal synthesis of (+)-epijuvabione.

The first example of the boron Lewis acid catalyzed Csp2–H functionalization of cyclic enones was achieved using diazoacetates. The insertion of the carbon atom of diazoacetates utilizes BF3•Et2O or a newly designed oxazaborolidinium ion as a catalyst to afford β-functionalized cyclic enones from simple cyclic enones in a single step and high yields. The reaction mechanism was investigated with deuterium labeled 2-cyclohexen-1-one.

A metabolomic analysis was performed to examine the postharvest processing of Astragalus membranaceus roots with a focus on the peeling procedure using 1H NMR and UPLC-MS analyses. Principal component analysis (PCA) score plots from the 1H NMR and UPLC-MS data showed clear separation between peeled and unpeeled Astragalus roots. Peeled roots exhibited significant losses of several primary metabolites, including acetate, alanine, arginine, caprate, fumarate, glutamate, histidine, N-acetylaspartate, malate, proline, sucrose, trigonelline, and valine. In contrast, the peeled roots contained higher levels of asparagine, aspartate, and xylose, which are xylem-related compounds, and formate, which is produced in response to wound stress incurred during postharvest processing. In addition, the levels of isoflavonoids and astragalosides were significantly reduced in peeled Astragalus root. These results demonstrate that metabolite profiling based on a combination of 1H NMR and UPLC-MS analyses can be used to evaluate peeling procedures used in the postharvest processing of herbal medicines.

A simple and efficient method for the asymmetric synthesis of α-alkylidene-β-hydroxy-γ-butyrolactones and related natural products was developed on the basis of the catalytic asymmetric tandem Michael–aldol reaction and simple transformations. The synthetic utility of this method was illustrated by the facile synthesis of trisubstituted γ-butyrolactone natural products.

Novel iridium(III) complexes containing bis(N-heterocyclic carbene), bis(imidazoline thione) L2, and bis(imidazoline selone) L3 were prepared. The iridium complexes bearing L2 and L3 showed the significant absorption of visible light with maximum intensity at ∼460 nm. Bis(2-(2′-benzothienyl)pyridinato)iridium(III) complexes (Ir-6) with L3 showed excellent ability as a photosensitizer of visible light. Under blue LED irradiation with maximum emission at 460 nm, 0.25 mol % Ir-6 showed 94% conversion of benzylamine for 5 h at room temperature. Through mechanistic studies, it was suggested that the photoinduced oxidative coupling of benzylamine by Ir-6 follows a singlet oxygen pathway. The excellent performance of Ir-6 originated from the efficient visible light absorption at 460 nm and the enhanced triplet state due to the heavy-atom effect of L3. This work shows that bis(imidazoline thione) and bis(imidazoline selone) can be efficient ligands for tuning the optical properties of iridium(III) complexes.

Total synthesis of (+)-ambuic acid has been accomplished from the readily available stereocontrolled Diels–Alder adduct of cyclopentadiene and iodo-1,4-benzoquinone monoketal through an efficient series of steps. A new method for the highly commendable synthesis of α-brominated Diels–Alder adduct is described.

A catalytic synthetic route to highly functionalized chiral cyclopropane derivatives was developed by Michael-initiated cyclopropanation of α-substituted acroleins with aryl- and alkyl diazoacetates. In the presence of chiral (S)-oxazaborolidinium cation 1b as a catalyst, the reaction proceeded in high yield (up to 93%) with high to excellent diastereoselectivity (up to 98% de) and enantioselectivity (up to 95% ee).

An unprecedented high level of regioselectivities (up to 96%) in the intermolecular crossed acyloin condensations of various aromatic aldehydes with acetaldehyde was realized by an appropriate choice of N-heterocyclic carbene catalysts.

Tuberculosis (TB) is one of three major infectious diseases, and the control of TB is becoming more difficult because of the emergence of multidrug-resistant and extensively drug-resistant strains. In this study, we explored the 1H NMR-based metabolomics of TB using an aerobic TB infection model. Global profiling was applied to characterize the responses of C57Bl/6 mice to an aerobic infection with virulent Mycobacterium tuberculosis (MTB). The metabolic changes in organs (i.e., the lung, the target organ of TB, and the spleen and liver, remote systemic organs) and in serum from control and MTB-infected rats were investigated to clarify the host–pathogen interactions in MTB-infected host systems. Principal components analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots showed distinct separation between control and MTB-infected rats for all tissue and serum samples. Several tissue and serum metabolites were changed in MTB-infected rats, as compared to control rats. The precursors of membrane phospholipids, phosphocholine, and phosphoethanolamine, as well as glycolysis, amino acid metabolism, nucleotide metabolism, and the antioxidative stress response were altered based on the presence of MTB infection. This study suggests that NMR-based global metabolite profiling of organ tissues and serum could provide insight into the metabolic changes in host infected aerobically with virulent Mycobacterium tuberculosis.

A facile method for the intermolecular Stetter reaction of various Michael acceptors with acetaldehyde as a biomimetic acylanion source was realized using N-heterocyclic carbene catalysis. This catalytic system has also been applied to the enantioselective Stetter reaction and resulted in moderate to good enantioselectivities for the corresponding Stetter products.

A cationic oxazaborolidinium-catalyzed asymmetric Mukaiyama aldol reaction of (1-methoxy-2-methyl-propenyloxy)-trimethylsilane with various aldehydes including α,β-disubstituted acroleins has been developed in high yields and enantioselectivities. The synthetic utility of this methodology was demonstrated in the first short synthesis of naturally occurring inthomycin C in high enantiopurity.

A convenient synthetic method for enantioenriched (E)-α-alkylidene-β-amino esters has been developed through thermal Overman rearrangement. Readily accessible (Z)-β-branched Morita−Baylis−Hillman esters serve as chiral pool precursors. Thermal rearrangement proceeded through a concerted pseudopericyclic transition state to produce (E)-stereoselective products. We expanded the synthetic utilities of α-alkylidene-β-amino esters via preparation of α-alkylidene-β-lactam derivatives.

The geographical origin of beef is of increasing interest to consumers and producers due to “mad cow” disease and the implementation of the Free Trade Agreement (FTA). In this study, 1H NMR spectroscopy coupled with multivariate statistical analyses was used to differentiate the geographical origin of beef samples. Principal component analysis (PCA) and orthogonal projection to latent structure−discriminant analysis (OPLS-DA) showed significant separation between extracts of beef originating from four countries: Australia, Korea, New Zealand, and the United States. The major metabolites responsible for differentiation in OPLS-DA loading plots were succinate and various amino acids including isoleucine, leucine, methionine, tyrosine, and valine. A one-way ANOVA was performed to statistically certify the difference in metabolite levels. The data suggest that NMR-based metabolomics is an efficient method to distinguish fingerprinting difference between raw beef samples, and several metabolites including various amino acids and succinate can be possible biomarkers for discriminating the geographical origin of beef.

A catalytic route to highly functionalized chiral 2-pyrazolines by an asymmetric 1,3-dipolar cycloaddition reaction of ethyl diazoacetate with α-substituted and α,β-disubstituted acroleins has been developed; in the presence of chiral (S)-oxazaborolidinium ion 1 as catalyst, the reaction proceeded with high to excellent enantioselectivities (up to 99% ee).

(+)-cis-Nemorensic acid (1) was synthesized from a chiral Diels–Alder adduct (4) prepared by a catalytic enantioselective Diels–Alder reaction with 2,5-dimethylfuran and 2,2,2-trifluoroethyl acrylate.

This paper describes a catalytic enantioselective route to synthesize functionalized all-carbon quaternary acyclic systems via a boron Lewis acid-promoted formal C–C insertion of diazoesters into aryl-CHO bonds. In the presence of chiral (S)-oxazaborolidinium cation 1d as a catalyst, the reaction proceeded in good yield (up to 83%) with good regioselectivity (up to 88:12) and excellent enantioselectivity (up to 99% ee). The synthetic potential of this method was illustrated by conversion of the products to both α- and β-amino esters.

(+)-cis-Nemorensic acid (1) was synthesized from a chiral Diels–Alder adduct (4) prepared by a catalytic enantioselective Diels–Alder reaction with 2,5-dimethylfuran and 2,2,2-trifluoroethyl acrylate.

A catalytic route to highly functionalized chiral 2-pyrazolines by an asymmetric 1,3-dipolar cycloaddition reaction of ethyl diazoacetate with α-substituted and α,β-disubstituted acroleins has been developed; in the presence of chiral (S)-oxazaborolidinium ion 1 as catalyst, the reaction proceeded with high to excellent enantioselectivities (up to 99% ee).

Highly enantioselective 1,3-dipolar cycloaddition reactions of α-substituted diazoacetates are accomplished by catalysis of the chiral oxazaborolidinium ion. Functionalized 2-pyrazolines are synthesized in high to excellent enantiomeric ratios (up to >99:1). The synthetic utility of 2-pyrazoline was expanded via preparation of 2,4-diamino ester compounds bearing a chiral quaternary carbon center.

A facile method for the intermolecular Stetter reaction of various Michael acceptors with acetaldehyde as a biomimetic acylanion source was realized using N-heterocyclic carbene catalysis. This catalytic system has also been applied to the enantioselective Stetter reaction and resulted in moderate to good enantioselectivities for the corresponding Stetter products.