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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.

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.).

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 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.

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.

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.

SummaryBackground 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. Objective We applied a 1H-NMR metabolomics approach to investigate the altered metabolic pattern in sera from patients with asthma and sought to identify the mechanism underlying asthma and potential biomarkers. Method A global profile of sera from patients with asthma (n = 39) and controls (n = 26) was generated using 1H-NMR spectroscopy coupled with multivariate statistical analysis. Endogenous metabolites in serum were rapidly measured using the target-profiling procedure. Results Multivariate statistical analysis showed a clear distinction between patients with asthma and healthy subjects. Sera of asthma patients were characterized by increased levels of methionine, glutamine, and histidine and by decreased levels of formate, methanol, acetate, choline, O-phosphocholine, arginine, and glucose. The metabolites detected in the sera of patients with asthma are involved in hypermethylation, response to hypoxia, and immune reaction. Furthermore, the levels of serum metabolites from patients with asthma correlated with asthma severity; in particular, lipid metabolism was altered in patients with lower forced expiratory volume in 1 s percentage (FEV1%) predicted values. In addition, potential biomarkers showed strong predictive power in ROC analysis, and the presence of asthma in external validation models was predicted with high accuracy (90.9% for asthma and 100% for control subjects). Conclusion & Clinical Relevance These data showed that 1H-NMR-based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.

The preparation of the catalysts is described as well as their highly effective use in the title reaction of aryl or alkyldithiomalonates with β-aryl or alkyl substituted nitroolefins.

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 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).

A catalytic route toward chiral α-alkyl-β-ketoesters using the title reaction of α-alkyl diazoester with aldehydes is developed.

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.

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.

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.

We found that chemoselectivity of the crossed acyloin product is controlled by the adjustment of the aromatic aldehyde/aliphatic aldehyde ratio. Moreover, we observed the persistent catalytic activity of the homogeneous NHC catalyst in a solution due to NHC catalyst robustness.

The first example of a highly enantioselective catalytic C—C insertion of diazoesters into aldehydes affords functionalized acyclic all-carbon α-quaternary aldehydes.

The first example of the highly enantiocontrolled catalytic C(sp2)—H functionalization reaction of cyclic enones with diazoacetates is presented.

A novel Lewis acid-promoted Csp2-H functionalization reaction of cyclic enones using various diazoacetates is described.

This is a simple and efficient method for the asymmetric synthesis of the title compounds (V), a common motif in natural products.

A catalytic route toward chiral α-alkyl-β-ketoesters using the title reaction of α-alkyl diazoester with aldehydes is developed.

A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c-nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg−1 per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, ×0.3), hippurate (×0.3) and taurine (×0.6) decreased significantly (P

The reaction of various Michael acceptors with acetaldehyde as a complementary method to the enzymatic generation of an acylanion is developed.

An efficient and enantioselective Mukaiyama aldol reaction between ketene silyl acetals and a variety of aldehydes is developed using OAB as catalyst.

The rearrangement of various racemic hydroxycarboxylic ester substrates is investigated in the presence of (II) to give the (E)-configurated amino acid esters nearly exclusively.

Efficient syntheses of statine and its analogues have been attained from aziridine diols 3 and ent- 3 , which were prepared via iodocyclization of trichloroacetimidates of chiral 3-buten-1,2-diols 1 and ent- 1 .

Alkenic diols 2 and 14 are iodocyclized providing dihydro-1,3-oxazine 3 and dihydrooxazole 15 in 90 and 93% de, respectively, which are precursors of various C2 symmetric and meso-amino alcohols.

C 2 Symmetric and meso -iodo hydroxy ammonium chlorides generated from 2 and 5 have been cyclized under basic conditions to produce various heterocycles chemoselectively, which comprise tetrahydrofurans 7 and 19 , piperidines 13, 15 and 21 , and pyrrolidines 17 and 18 .

(+)-Bromoxone (VII) is prepared via an enantioselective Diels—Alder reaction of quinone ketal (I), a selective exo-epoxidation of derivative (IV) and a retro-Diels—Alder reaction of epoxide (V) as key steps.

We describe a rapid and efficient method for selective deprotection of methoxymethyl (MOM) ethers using ZnBr2 and n-PrSH, which completely removed MOM from diverse MOM ethers of primary, secondary, and tertiary alcohols or phenol derivatives. The deprotection takes less than ten minutes with both high yield and selectivity in the presence of other protecting groups. In addition, the rapid deprotection of MOM ethers of tertiary hydroxyls in high yield with no epimerization allows MOM to be a suitable protecting group for tertiary alcohols.

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.

This work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2005-070-C00073, KRF-2008-331-C00160) and by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. R01- 2008-000-11094-0) and by KBSI grant (N28043) to G.-S. Hwang.

Korea Basic Science Institute, 5 St, Anam-Dong, Seongbuk-Gu, Seoul 136-713, KoreaReceived July 17, 2008Key Words : Asymmetric sulfoxidation, Salen-Mn catalyst, Esomeprazole The asymmetric synthesis of sulfoxides has received parti-cular attention in recent years due to their excellent stereo-chemical control as chiral auxiliaries in a variety of highlydiastereoselective carbon-carbon bond forming reactions,including the synthesis of chiral amines, amino acids, aziri-dines, and amino phosphoric acids.

The enantioselective formal synthesis of a natural antitumor product, (+)-ottelione A, was achieved through a catalytic enantioselective Diels–Alder strategy. These endeavors have led to the synthesis of a variety of synthetic analogues of this biologically potent natural product.