In the presence of a catalytic amount of VO(acac) 2 , oxidative coupling of 2-naphthol or phenol derivatives with molecular oxygen occurred at room temperature and selectively gave the corresponding ortho-ortho coupling products in moderate to high yields.

1 Hydroxychavicol (HC; 10 ± 50 mM), a betel leaf component, was found to suppress the 2% H 2 O 2 -induced lucigenin chemiluminescence for 53 ± 75%. HC (0.02 ± 2 mM) was also able to trap superoxide radicals generated by a xanthine/xanthine oxidase system with 38 ± 94% of inhibition. Hydroxyl radicals-induced PUC18 plasmid DNA breaks was prevented by HC (1.6 ± 16 mM). 2 A 24-h exposure of KB cells to HC (0.5, 1 mM) resulted in 54 ± 74% cell death as analysed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. HC (10, 50 mM) further suppressed the growth of KB cells (15 and 76%, respectively). Long-term colony formation of KB cells was inhibited by 51% with 10 mM HC. 3 Pretreatment of KB cells with 100 mM HC inhibited the attachment of KB cells to type I collagen and ®bronectin by 59 and 29%, respectively. 4 Exposure of KB cells to 0.1 mM HC for 24 h resulted in cell cycle arrest at late S and G2/M phase. Increasing the HC concentration to 0.25 and 0.5 mM led to apoptosis as revealed by detection of sub-G 0 /G 1 peaks with a concomitant decrease in the number of cells residing in late S and G 2 /M phase. 5 Inducing the apoptosis of KB cells by HC was accompanied by marked depletion in reduced form of GSH (40.2 mM) and the increasing of reactive oxygen species production (40.1 mM) as analysed by CMF-and DCF-single cell¯uorescence¯ow cytometry. 6 These results indicate that HC exerts antioxidant property at low concentration. HC also inhibits the growth, adhesion and cell cycle progression of KB cells, whereas its induction of KB cell apoptosis (HC40.1 mM) was accompanied by cellular redox changes.

Reducing the choices. Cu(OTf)2 is an efficient and dual‐purpose catalyst for the highly regioselective reductive ring openings of benzylidene acetals with either BH3 or Me2EtSiH to give the corresponding primary and secondary alcohols (see scheme). Isotope studies have confirmed that both modes of ring cleavage proceed by an SN1 reaction pathway when borane or silane attack the acetal carbon center.

No abstract

Optically active cyanohydrins are synthetic precursors of R-hydroxy carboxylic acids, R-amino carboxylic acids, β-hydroxy amines, and several other classes of organic compounds of biological importance. Existing methods for the preparation of chiral cyanohydrins include both enzymatic 1,2 and chemical processes. 1,3 Chemically, several efficient methods have been developed. In most of these methods, however, the chiral ligands are rather unstable and cannot be easily recovered. We now describe a new chiral Ti(IV) catalyst with dihydroxy-trans-1,2-diamide 3a as the ligand, which effects the enantioselective addition of trimethylsilyl cyanide to aldehydes.Ligand 3a and its diastereoisomer 3b were prepared from ketopinic acid chloride (1) 4 according to the Scheme 1. On treatment with optically pure (+)-or (-)-trans-1,2-diaminocyclohexane in dichloromethane in the presence of triethylamine, ketopinic acid chloride was converted to the trans-diketoamide 2a or 2b, respectively. Diketoamide 2a and 2b could also be obtained in pure form by reacting ketopinic acid chloride with (+)-trans-1,2-diaminocyclohexane in the same fashion as above followed by separation of the resulting diastereomeric mixture by column chromatography on silica gel. Subsequent reduction of 2a and 2b using L-selectride in tetrahydrofuran at -78 °C for 1 h and then at room temperature for 2 h gave 3a and 3b, respectively with the hydroxy group at the exo position. 5 The absolute stereochemistry of ligand 3a was further determined by X-ray crystallographic analysis. Ligand 3a was found to be an useful chiral ligand for asymmetric induction (eq 1). In conjunction with titanium tetraisopropoxide, ligand 3a was shown to effect the enan-

A facile VO(acac)(2)-catalyzed in situ generation of iminium ions from amine N-oxides and their participation in a modified Mannich-type reaction is described.

The therapeutic effect of pterosin A, a small-molecular-weight natural product, on diabetes was investigated. Pterosin A, administered orally for 4 weeks, effectively improved hyperglycemia and glucose intolerance in streptozotocin, high-fat diet–fed, and db/db diabetic mice. There were no adverse effects in normal or diabetic mice treated with pterosin A for 4 weeks. Pterosin A significantly reversed the increased serum insulin and insulin resistance (IR) in dexamethasone-IR mice and in db/db mice. Pterosin A significantly reversed the reduced muscle GLUT-4 translocation and the increased liver phosphoenolpyruvate carboxyl kinase (PEPCK) expression in diabetic mice. Pterosin A also significantly reversed the decreased phosphorylations of AMP-activated protein kinase (AMPK) and Akt in muscles of diabetic mice. The decreased AMPK phosphorylation and increased p38 phosphorylation in livers of db/db mice were effectively reversed by pterosin A. Pterosin A enhanced glucose uptake and AMPK phosphorylation in cultured human muscle cells. In cultured liver cells, pterosin A inhibited inducer-enhanced PEPCK expression, triggered the phosphorylations of AMPK, acetyl CoA carboxylase, and glycogen synthase kinase-3, decreased glycogen synthase phosphorylation, and increased the intracellular glycogen level. These findings indicate that pterosin A may be a potential therapeutic option for diabetes.

Herein we reveal a simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in-house compound library to select compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in-house compound library collection prior to testing. Five new series of Aurora kinase inhibitors were identified through this strategy, with IC(50) values ranging from approximately 300 nM to approximately 15 microM, by testing only 133 compounds from a database of approximately 125,000 compounds. Structure-activity relationship studies and X-ray co-crystallographic analysis of the most potent compound, a furanopyrimidine derivative with an IC(50) value of 309 nM toward Aurora kinase A, were carried out. The knowledge gained through these studies could help in the future design of potent Aurora kinase inhibitors.