Do Hyun Ryu

Highly Enantioselective Cyanosilylation of Aldehydes Catalyzed by a Chiral Oxazaborolidinium Ion

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).

1H-NMR-based metabolomics study of cerebral infarction.

Background and Purpose— Stroke is one of the leading causes of adult disability and death in developing countries. However, early diagnosis is difficult and no reliable biomarker is currently available. Thus, we applied a 1H-NMR metabolomics approach to investigate the altered metabolic pattern in plasma and urine from patients with cerebral infarctions and sought to identify metabolic biomarkers associated with stroke. Methods— Metabolic profiles of plasma and urine from patients with cerebral infarctions, especially small vessel occlusion, were investigated using 1H-NMR spectroscopy coupled with multivariate statistical analysis, such as principal components analysis and orthogonal partial least-squares discriminant analysis. Results— Multivariate statistical analysis showed a significant separation between patients and healthy individuals. The plasma of stroke patients was characterized by the increased excretion of lactate, pyruvate, glycolate, and formate, and by the decreased excretion of glutamine and methanol; the urine of stroke patients was characterized by decreased levels of citrate, hippurate, and glycine. These metabolites detected from plasma and urine of patients with cerebral infarctions were associated with anaerobic glycolysis, folic acid deficiency, and hyperhomocysteinemia. Furthermore, the presence of cerebral infarction in the external validation model was predicted with high accuracy. Conclusions— These data demonstrate that a metabolomics approach may be useful for the effective diagnosis of cerebral infarction and for the further understanding of stroke pathogenesis.

(1)H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis.

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 (1)H 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.

Oxazaborolidinium Ion-Catalyzed Cyclopropanation of α-Substituted Acroleins: Enantioselective Synthesis of Cyclopropanes Bearing Two Chiral Quaternary Centers

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).

Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis

Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify the pathogenesis of asthma by systemic review.

1H nuclear magnetic resonance based metabolic urinary profiling of patients with ischemic heart failure

OBJECTIVES We sought to identify metabolic pathways characterizing human heart failure (HF) using ¹NMR based urinary metabolomic analysis in conjunction with multivariate statistics. DESIGN AND METHODS Patients with systolic HF of ischemic origin (n=15) and healthy controls (n=20) participated in this study. Patients with type 2 diabetes mellitus were excluded. RESULTS The results showed that the urine of the HF patients had higher levels of metabolites for acetate (p<0.05) and acetone (p<0.01) compared to the healthy controls. In addition, there was a perturbation in methylmalonate metabolism as shown by increased urinary levels of methylmalonic acid (p<0.001) in the HF patients. HF patients also had increased urinary levels of cytosine (p<0.01) and phenylacetylglycine (p<0.01) and decreased 1-methylnicotinamide (p<0.05) compared to healthy controls. CONCLUSIONS TCA cycle metabolites and fatty acid metabolism were modified in the HF patients, indicating altered energy metabolism. Moreover, perturbations of metabolism in nucleotide and methylmalonate were observed.

Aminoglycoside binding to human and bacterial A-Site rRNA decoding region constructs

The 16S bacterial ribosomal A-site decoding rRNA region is thought to be the pharmacological target for the aminoglycoside antibiotics. The clinical utility of aminoglycosides could possibly depend on the preferential binding of these drugs to the prokaryotic A-site versus the corresponding A-site from eukaryotes. However, quantitative aminoglycoside binding experiments reported here on prokaryotic and eukaryotic A-site RNA constructs show that there is little in the way of differential binding affinities of aminoglycosides for the two targets. The largest difference in affinity is 4-fold in the case of neomycin, with the prokaryotic A-site construct exhibiting the higher binding affinity. Mutational studies revealed that decoding region constructs retaining elements of non-Watson-Crick (WC) base pairing, specifically bound aminoglycosides with affinities in the muM range. These studies are consistent with the idea that aminoglycoside antibiotics can specifically bind to RNA molecules as long as the latter have non-A form structural elements allowing access of aminoglycosides to the narrow major groove.

Photocatalysis by phenothiazine dyes: visible-light-driven oxidative coupling of primary amines at ambient temperature.

New phenothiazine based organic dyes were prepared for visible-light-driven organic transformations. The 3,7-disubstituted phenothiazine derivatives showed visible light absorption and reversible one-electron oxidation behavior. In the presence of 0.5 mol % of 3,7-disubstituted phenothiazines, primary benzylamines showed oxidative coupling under visible light irradiation from a blue LED. The electronic effect of substituents in phenothiazine dyes was observed in catalytic activities. The mechanistic pathway of oxidative coupling was discussed based on the detection of H(2)O(2) after the reaction.

Switching regioselectivity in crossed acyloin condensations between aromatic aldehydes and acetaldehyde by altering n -heterocyclic carbene catalysts

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.

Enantioselective Synthesis of β-Iodo Morita–Baylis–Hillman Esters by a Catalytic Asymmetric Three-Component Coupling Reaction†

A catalytic route toward chiral Morita-Baylis-Hillman esters by asymmetric coupling between alpha,beta-acetylenic esters, aldehydes, and trimethylsilyl iodide has been developed (see scheme). The reaction proceeds with high to excellent enantioselectivities, and the products can be transformed into beta-branched derivatives in a single step and with excellent retention of configuration. TMS = trimethylsilyl.