High diastereo- and enantioselective Michael addition of 3-acetoxy-2-oxindoles with nitroalkenes catalyzed by nickel/PyBisulidine.

A Ni/PyBisulidine catalyzed asymmetric Michael addition of 3-acyloxy-2-oxindoles to nitroalkenes has been developed. Various quaternary substituted 3-acyloxy-2-oxindoles were obtained with excellent yields and diastereo- and enantioselectivities in a low-toxic green solvent, ethyl acetate, with a low catalyst loading (1 mol%). The reaction process is air and moisture tolerant. The substrate scope was also extended to α,ß-disubstituted nitroalkenes and 3-hydroxy-2-oxindoles, and good results were obtained.

Facile construction of dibenzodioxo[3.3.1]nonanes bearing spirocyclohexadienones via domino [4 + 2] cycloaddition/C(sp3)-H oxidative dehydrogenation coupling reactions.

A novel palladium catalyzed homodimerization of ortho-hydroxyphenyl substituted p-QMs has been developed via [4 + 2] cycloaddition/oxidative dehydrogenation coupling domino reactions. An interesting palladium catalyzed intramolecular benzyl C-H oxidation dehydrogenation to form a transannular C(sp3)-O bond was found. This protocol provided an efficient method to construct various dibenzodioxo[3.3.1]nonanes bearing spirocyclohexadienones.

Cooperative Heterobimetallic Zinc/Alkaline Earth Metal Catalysis: A Zn/Sr Aminophenol Sulfonamide Complex for Catalytic Asymmetric Michael Addition of 3-Acetoxy-2-oxindoles to ß-Ester Enones.

A heterobimetallic zinc/strontium catalyst has been developed for the asymmetric Michael addition of 3-acetoxy-2-oxindoles to ß-ester enones in high yields with excellent enantioselectivities and high diastereoselectivities. This process represents that 3-acetoxy-2-oxindoles can be used as a stable air- and base-tolerant precursor for chiral 3-substituted 3-hydroxy-2-oxindoles.

Organocatalytic asymmetric cascade 1,6-addition/hemiketalization/retro-Henry reaction of ortho-hydroxyphenyl-substituted p-QMs with α-nitroketones.

A novel organocatalytic asymmetric cascade 1,6-addition/hemiketalization/retro-Henry reaction of ortho-hydroxyphenyl-substituted p-QMs with α-nitroketones is described. A variety of novel chiral 2-(1-(4-hydroxyphenyl)ethyl)phenols are constructed for the first time with high yields (up to 92%) and excellent enantioselectivities (up to >99% ee) under mild reaction conditions. A gram-scale experiment of this process is also presented.

A homodinuclear cobalt complex for the catalytic asymmetric Michael reaction of ß-ketoesters to nitroolefins.

A homodinuclear Co2/aminophenol sulfonamide complex has been developed for the asymmetric Michael reaction of ß-ketoesters with nitroolefins. This procedure is capable of tolerating a wide range of substrates and excellent results (up to 99% yield, >99 : 1 dr and 98% ee) can also be obtained. Moreover, the reaction could be carried out on a 50 mmol scale without any decrease in the enantioselectivity and reactivity. On the basis of the results of mechanistic studies, we proposed that the Co2/2a complex would be the active species and a possible catalytic cycle was described.

An Ni-PyBisulidine complex for the asymmetric hydrophosphonylation of aldehydes.

A novel Ni-PyBisulidine complex has been developed for the asymmetric hydrophosphonylation of aldehydes. A variety of aromatic, heteroaromatic, condensed-ring, α,ß-unsaturated, and aliphatic aldehydes are found to be suitable substrates for the reaction, and the desired α-hydroxy phosphonates are obtained in up to 99% yield and 97% ee.

The protective effect of caffeic acid on global cerebral ischemia-reperfusion injury in rats.

Ischemic stroke is a major cause of death and disability all over the world. Ischemic stroke results from a temporary or permanent reduction of cerebral blood flow that leads to functional and structural damage in different brain regions. Despite decades of intense research, the beneficial treatment of stroke remains limited. In light of this, the search for effective means ameliorating cerebral ischemia-reperfusion injury (CIRI) is one of the major problems of experimental medicine and biology. Recently, the 5-Lipoxygenase (5-LO, a key enzyme metabolizing arachidonic acid to produce leukotrienes) inhibitors have been showed to protect brain against ischemic damage in animal model of cerebral ischemia. Caffeic acid, an inhibitor of 5-LO, is a phenolic compound widely distributed in medicinal plants. The aim of this study was to investigate the effect of caffeic acid on global cerebral ischemia-reperfusion injury in rats. The study was carried out on 45 rats that were randomly divided into five groups: the sham group (n = 9), I/R non-treated group (n = 9), I/R-caffeic acid group (10 mg · kg(-1)) (n = 9), I/R-caffeic acid group (30 mg · kg(-1)) (n = 9) and I/R-caffeic acid group (50 mg · kg(-1)) (n = 9). Global cerebral ischemia was induced by bilateral carotid artery occlusion for 20 min followed by reperfusion. Spatial learning and memory was evaluated using Morris water maze. Histopathological changes of hippocampus neurons was observed using HE staining. Superoxide dismutase (SOD, the antioxidant enzyme) activities and malondialdehyde (MDA, an oxidative stress biomarker) contents were detected. NF-κBp65 expression was detected by the methods of immunohistochemistry. Caffeic acid markedly reduced the escape latency, relieved hippocampal neurons injury and increased neuron count compared with those of I/R non-treated rat. NF-κBp65 expression and MDA content decreased significantly, and SOD activities increased significantly in hippocampus. Compared with sham group, 5-LO expression increase significantly in I/R non-treated group rat, and caffeic acid markedly reduced 5-LO expression. The results of the study suggest that caffeic acid has a significant protective effect on global cerebral ischemia-reperfusion injury in rats. The neuroprotective effects is likely to be mediated through the inhibition of 5-LO.

Divergent oxidative dearomatization coupling reactions to construct polycyclic cyclohexadienones.

Highly selective divergent oxidative dearomatization coupling reactions, in which the chemoselectivity is controlled by catalysts and bases, are reported herein. Three different kinds of polycyclic cyclohexadienones are produced from the same reactants (41 examples, 85-99% yield). Our method marks a novel copper- and palladium-catalyzed C-H oxidative dearomatization of phenolic derivatives.

rac-tert-Butyl 2-{5-[(4-{2-[methyl(pyri-din-2-yl)amino]ethoxy}phenyl)methyl]-2,4-dioxo-1,3-thiazolidin-3-yl}acetate.

The title compound, C(24)H(29)N(3)O(5)S, is a chiral mol-ecule which crystallizes in a centrosymmetric space group as a racemate. The thia-zolidine ring forms the dihedral angles of 29.22 (12) and 67.79 (10)° with the benzene and pyridine rings, respectively. The benzene and pyridine rings are tilted by dihedral angle of 67.18 (9)°. In the crystal, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into a two-dimensional network.

Catalytic enantioselective Henry reaction of α-keto esters, 2-acylpyridines and 2-acylpyridine N-oxides.

A pre-prepared Ni-PyBisulidine complex has been developed for the catalytic asymmetric Henry reaction of α-keto esters, 2-acylpyridines and 2-acylpyridine N-oxides. The corresponding ß-nitro-α-hydroxy esters were obtained in good to excellent yields (up to 99%) with a high enantiomeric excess (ee) (up to 94%) with a catalyst loading of 1-2 mol%. The desired products of 2-acylpyridines and 2-acylpyridine N-oxides, which were simple methyl ketones, were obtained in medium to excellent yields (up to 94%) with medium to good ee (up to 86%) by using 2 mol% of catalyst.

Re-evaluation of the interrelationships among the behavioral tests in rats exposed to chronic unpredictable mild stress.

The chronic unpredictable mild stress model of depression has been widely used as an experimental tool to investigate human psychopathology. Our objective was to provide an update on the validity and reliability of the chronic unpredictable mild stress model, by analyzing the interrelationships among the indexes using stepwise discriminant analysis and Pearson correlation coefficient to examine the possible combinations. We evaluated the depressive rats in both the presence and the absence of chronic unpredictable mild stress, using weight change, percentage of sucrose preference, coat state, splash test, open-field test, elevated plus-maze test, forced swimming test, and Morris water maze test. The results showed that 6-week-long chronic unpredictable mild stress produces significant depression and anxiety-like behavior. The combination of body weight change, percentage of sucrose preference, coat state score, open-field score, grooming latency of splash test, immobility time in force swimming test, and platform crossing in the Morris water maze test can effectively discriminate between normal and chronic unpredictable mild stress rats. Strong interrelationships were noted among these indexes in both open-field test and elevated plus-maze test. In conclusion, there might be certain criteria for the combination of behavioral endpoints, which is advantageous to more effectively and reliably assess the chronic unpredictable mild stress induced depression model.

A novel homobimetallic nickel complex for the asymmetric direct Mannich reaction of imines: a practical method on a multi-gram scale.

A novel dinuclear Ni complex has been developed for the direct Mannich reaction of malonates with N-tosyl aryl imines with a low catalyst loading (0.1-0.05 mol%) on a preparative scale (5-50 mmol). The structure of the active species was verified via control experiments, ESI-HRMS, and DFT calculations.

The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.

The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver. Aluminium also significantly increased the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and the levels of inflammation and oxidative stress, while significantly decreased the EP3 expression in liver. The administration of meloxicam significantly improved the impairment of liver. The contents of prostaglandin E2 and cyclic adenosine monophosphate were significantly decreased by administration of meloxicam. The administration of meloxicam also significantly decreased the expressions of cyclooxygenases-2 and protein kinase A and the levels of inflammation and oxidative stress, while significantly increased the EP1,2,3,4 expressions in rat liver. Our results suggested that the imbalance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved in the injury of chronic aluminium-overload rat liver. The protective mechanism of meloxicam on aluminium-overload liver injury is attributed to reconstruct the balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.

Effect of the PGD2-DP signaling pathway on primary cultured rat hippocampal neuron injury caused by aluminum overload.

In the present study, the agonists and antagonists of DP receptor were used to examine whether the PGD2-DP signaling pathway affects neuronal function. Primary cultured hippocampal neuron was prepared and treated with aluminum maltolate (100 µM) to establish the neuronal damage model. PGD2 and cAMP content was detected by ELISA. L-PGDS and DPs mRNA and protein expression were measured by RT-PCR and Western blotting, respectively. The aluminium-load neuron was treated with the DP1 agonist BW245C, the DP1 antagonist BWA868C, the DP2 agonist DK-PGD2, and the DP2 antagonist CAY10471, respectively. Neuronal pathomorphology was observed using H-E staining. The cell viability and the lactate dehydrogenase leakage rates of neurons were measured with MTT and LDH kit, respectively. Ca(2+) level was detected by Fluo-3/AM. In the model group, the MTT values obviously decreased; LDH leakage rates and PGD2 content increased significantly; L-PGDS, DP1 mRNA and protein expressions increased, and DP2 level decreased. BW245C reduced the Ca(2+) fluorescence intensity and protected the neurons. DK-PGD2 increased the intensity of Ca(2+) fluorescence, while CAY10471 had the opposite effect. In conclusion, contrary to the effect of DP2, the PGD2-DP1 signaling pathway protects against the primary cultured rat hippocampal neuronal injury caused by aluminum overload.