Mechanistic Investigation on Rhodium(III)-Catalyzed Cycloaddition of 2-Vinylphenol Derivatives with Ethyne or Carbon Monoxide by DFT Study

Rhodium-catalyzed cycloaddition reaction was calculated by density functional theory M06-2X method to directly synthesize benzoxepine and coumarin derivatives.In this work,we conducted a computational study of two competitive mechanisms in which the carbon atom of acetylene or carbon monoxide attacked and inserted from two different directions of the six-membered ring reactant to clarify the principle characteristics of this transformation.The calculation results reveal that:(i)the insertion process of alkyne or carbon monoxide is the key step of the reaction;(ii)for the(5+2)cycloaddition reaction of acetylene,higher energy is required to break the Rh−O bond of the reactant,and the reaction tends to complete the insertion from the side of the Rh−C bond;(iii)for the(5+1)cycloaddition of carbon monoxide,both reaction paths have lower activation free energy,and the two will generate a competition mechanism.

Use of Ultrasound and Microwave Irradiation for Clean and Efficient Synthesis of 3,3’-(Arylmethylene)bis (2-hydroxynaphthalene-1,4-dione) Derivatives

Nine 3,3’-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) derivatives were synthesized through the reaction between 2-hydroxy-1,4-naphthalen-1,4-dione and different aromatic alde-hydes in water applying ultrasonic irradiation for 5 min at room temperature and microwave irradiation for 15 min at 70°;C. Two of the nine derivatives, compounds 3-e and 3-i, obtained from 3-bromo-hydroxybenzaldehyde and 5-methylfuran-2-carbaldehyde, respectively, are previously unpublished. The structures of all compounds were established on the basis of their spectral data and mass analysis. The attractive features of this synthesis protocol include mild conditions, high atom-economy and excellent yields with the elimination of water as the only by-product.

2D-QSAR Studies on Phenoxybenzoic Acid Derivatives: A Novel Class of 5a-Reductase Inhibitors

The quantitative structure-activity relationship （QSAR） of 14 phenoxybenzoic acid derivatives was studied by ab initio method at the HF/6-31G level using Guassian03 software. The optimized structures together with some characteristic and electric parameters of the title compounds were obtained; some stereo-parameters were calculated by HyperChem software. Stepwise multiple regression and principal component regression methods are adopted to establish multi-parametric models between biological activity and parameters. The results indicated that the lager Ehomo, M, V and LogP, the smaller Etumo and S, and the higher biological activity. A theoretical direction was provided to synthesize some compounds with high activity.

Synthesis,Crystal Structure and Biological Activity of 2-[(Pyridin-2-yl)methylthio]-1H-benzimidazole Derivatives

In order to discover the novel anti-tumor agents, a series of 2-[（pyridin-2-yl）methylthio]-1 H-benzimidazole derivatives were designed and synthesized, and the structures were characterized by IR, MS, and proton NMR. 2-[（3,4-Dimethoxypyridin-2-yl）methylthio]-1 Hbenzimidazole was investigated with X-ray crystallography, and the molecule is in orthorhombic system, space group P212121, with a = 9.1828（16）, b = 11.625（2）, c = 13.463（2） ？, Z = 4, R = 0.0231 and wR = 0.0596. The antitumor activities of target compounds were evaluated against human liver cancer cell line HepG2, and human liver normal cell line HL7702 using MTT assay. The target compounds have demonstrated weak or moderate anti-tumor activity against HepG2, while all the target compounds exhibit no cytotoxic effects on HL7702.

A Facile Synthesis of 9,10-Dimethoxybenzo[6,7]- ox-epino[3,4-<i>b</i>]quinolin-13(6<i>H</i>)-one and Its Derivatives

A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.

A new pyrrolidone derivative from Pistacia chinensis

A new N-phenyl-pyrrolidone derivative had been isolated from Pistacia chinesis Bunge. Its structure was elucidated as 4-hydroxy-5-（2-oxo-1-pyrrolidinyl）-benzoic acid, named pistaciamide on the basis of the 1D-NMR, DEPT, HMQC and HMBC spectroscopic techniques. 2007 Xi Kui Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

1,5-Dimethy-4-[(3-nitro-benzylidene)-amino]-2-pheyl-1,2-dihydro-pyrazol-3-one

The title compound C18H16N4O3 （Mr = 336.35） has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The Schiff base compound is a derivative of 4-aminoantipyrine. As expected, the molecular structure adopts a trans configuration about the central C=N double bond. It crystallizes in orthorhombic, space group P2dc with a = 7.632（1）, b = 7.816（1）, c = 28.082（5） A,β = 96.18（1）°, V= 1665.48（51） A^3, Z= 4, Dc = 1.341 g/cm^3, F（000） = 704,μ = 0.094 mm^-1, the final R = 0.0448 and wR = 0.1058. Of the total 3748 collections, 3105 were unique. In the molecule there exist two different planes of pyrazoline and C（11）-C（16） phenyl ring, which are approximately coplanar （r.m.s. de deviation from the combined mean plane is 0.03 A） with the dihedral angle between them of 9.8%.

Synthesis and Crystal Structure of 2,6-Bis(2-pyridinylmethyl)-3,5-bis(2-hydroxyl-5-chlorophenyl)pyrazine

The title compound,2,6-bis（2-pyridinylmethyl）-3,5-bis（2-hydroxyl-5-chlorophe nyl）-pyrazine（C26H12Cl2N4O2C2H8O2,Mr=551.41）,has been synthesized and characterized by LC-ESIMS,NMR,UV and IR spectroscopy as well as by X-ray single-crystal diffraction.The compound behaves as a substituted pyrazine.The hydrogen atoms on C（2） and C（3） are substituted by 2-pyridinyl,whereas those on C（1） and C（4） are substituted by 2-hydroxyl-5-chlorophenyl.It crystallizes in the monoclinic system,space group P21/c with a=8.9433（12）,b=32.003（4）,c=10.5209（18）,β=111.199（2）°,V=2807.5（7）3,Z=4,Dc=1.305 mg/m3,F（000）=1144 and μ=0.094 mm-1.A total of 13235 reflections were collected in the range of 2.17～25.01o by using a phi and omega scan mode,of which 4923 were unique（Rint=0.0692） and 2872 observed reflections with Ⅰ 〉2σ（Ⅰ） were used in the structure solution and refinement.

Solar Thermochemical Reactions IV: Unusual Reaction of Nitrones with Acetonitrile Derivatives Induced by Solar Thermal Energy

The behaviour of cyanothioacetamide 1 and the acetonitrile derivatives 6 and 10, respectively, towards the nitrones 2a-i induced by free solar thermal energy is reported. Structures and reaction mechanisms are also discussed.

4-[(Furan-2-ylmethylene)-amino]-1,5-dimethyl-1,2-dihyl-1,2-dihydo-pyrazol-3-one

The title compound （C16H15N3O2, Mr= 281.31） has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The Schiff base compound is a derivative of 4-aminoantipyrine. As expected, the molecular structure adopts a trans configuration about the C=N double bond. It crystallizes in the monoclinic system, space group P2 1/c with a = 11.150（3）, b = 9.906（3）, c = 13.624（4） A, β = 106.360（4）°, V= 1443.9（7） ,A^3, Z = 4, Dc = 1.294 g/cm^3, F（000） = 592,μ（MoKa） = 0.088 mm ^-1, R = 0.0577 and wR = 0.1214. Of the 5766 total reflections, 2540 were unique. In the molecule there exist two different planes of pyrazoline and O（2）-C（10） phenyl ring, which are approximately coplanar （r.m.s. de deviation from the combined mean plane is 0026 A） with the dihedral angle between them of 6.3°.

Formation of Hybrid Ring Structure of Cyanurate/Isocyanurate in the Reaction be-tween 2,4,6-Tris(4-Phenyl-Phenoxy)-1, 3,5-Triazine and Phenyl Glycidyl Ether

Reaction products of 2,4,6-tris(4-phenyl-phenoxy)-1,3,5-triazine derived from 4-phenylphenol cyanate ester and phenyl glycidyl ether were analyzed. In addition to an isocyanurate compound and an oxazolidone compound which were well known as reaction products of cyanate esters and epoxy resins, compounds with hybrid ring structure of cyanurate/isocyanurate were determined. Gibbs free energies of the compound having hybrid ring structure of cyanurate/isocyanurate with two isocyanurate moiety were found to be lower than that of the compound with cyanurate ring structure through calculations. Calculation data supported the existence of hybrid ring structure of cy-anurate/isocyanurate. It was revealed that isomerization from cyanurate to isocyanurate occurs via hybrid ring structure of cyanurate/isocyanurate in the reaction of aryl cyanurate and epoxy.

Decreased serum platelet derived growth factor BB levels in acute and increased in chronic pancreatitis

AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN).

Synthesis of （S）-2-Ethoxy-3-Phenylpropanoic Acid Derivatives and Their Insulin-Sensitizing Activity

A series of （S）-2-ethoxy-3-phenylpropanoic acid derivatives were synthesized and their insulin-sensitizing activities were evaluated in 3T3-L1 cells. Compounds 1b, 1d, 1e and 1f exhibited more potent insulin-sensitizing activity than rosiglitazone.

Design, synthesis and MAO inhibitory activity of 2-(arylmethylidene)-2,3-dihydro-1-benzofuran-3-one derivatives

A series of 2-（arylmethylidene）-2,3-dihydro-1-benzofuran-3-one derivatives（aurones, 1–20） were synthesized and screened for their inhibitory activity against h MAO. Seventeen compounds（1–5, 7–17,19） were found to be selective towards h MAO-B, while two were non-selective（6 and 20） and one（18）selective towards h MAO-A. Compound 17（Ki = 0.10 0.01 mmol/L） was found to be equally potent and selective towards h MAO-B, when compared with the standard drug Selegiline（Ki = 0.12 0.01 mmol/L）.Nature and position of substitution in aryl ring at 2nd position of benzofuranone influences h MAO-B inhibitory potency, while their structural bulkiness influences selectivity between h MAO-A and h MAO-B.Molecular docking simulation was also carried out to understand the interaction of inhibitor with the enzyme at molecular level, and we found the docking results were in good agreement with the experimental values. Comparison of the activity profile of the aurones with their corresponding flavones reported earlier by our group revealed that there exists no difference in potency as well as selectivity.

Synthesis of spiro-cyclopropane derivatives containing multiple chiral centers

Tandem asymmetric double Michael addition/internal nucleophilic substitution of the novel chiral source, 5-(l-menthyloxy)-3-bromo-2(5H)-furanone with nucleophilic alcohol compounds has been investigated. The tandem asymmetric reaction can afford four new stereogenic centers with one reaction and give optically pure spiro-cyclopropane derivatives 5a--5d which are difficult to obtain by routine methods. The synthetic method for 5a--5d was studied in detail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]^(20),IR,~1H NMR,^(13)C NMR, MS and elementary analysis. The absolute configuration of the sprio [5-l-menthyloxy-3-bromo butyrolactocyclopropane-3″, 3′(4′-methyloxy-5′-menthyloxybutyrolactone)] (5a) was established by X-ray crystallography. The work can provide important synthetic strategy in synthesis of some new optically active spiro-cyclopropane analogues and some biologically active molecules with complex structure.

Design, Synthesis and Biological Evaluation of Novel α-Acyloxycarboxamide-Based Derivatives as c-Met Inhibitors

Dysregulated HGF/c-Met signalling has been associated with many human cancers,poor clinical outcomes,and even resistance acquisition to some approved targeted therapies.As such,c-Met kinase has emerged as an attractive target for anticancer drug discovery.

肾靶向雷公藤内酯醇与2-氨基葡萄糖结合物的合成

目的合成雷公藤内酯醇与2-氨基葡萄糖的结合物(TPG)。方法将雷公藤内酯醇与丁二酸酐反应生成雷公藤内酯醇丁二酸单酯,其游离羧基与2-脱氧-2-氨基-D-吡喃葡萄糖氨基乙苷1位上的氨基形成酰胺键,得到TPG前药,并鉴定其结构。结果成功制备了TPG,其所含2-氨基葡萄糖具有肾靶向性,并改善了其水溶性。结论该前药的合成路线可行性高,TPG具有肾靶向性,雷公藤内酯醇的水溶性得到了改善。

Novel plant activators with thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate scaffold: Synthesis and bioactivity

The 1,2,3-thiadiazole-carboxylate moiety was reported to be an important pharmacophore of plant activators.In this study,a series of novel plant activators based on thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate were designed and synthesized and their biological activity as plant activators was studied.The structures of the novel compounds were identifed by1H NMR,19F NMR and HRMS.The in vivo bioassay showed that these novel compounds had good effcacy against seven plant diseases.Especially,compounds 1a and 1c were more potent than the commercialized plant activator BTH.Almost no fungicidal activity was observed for the active compounds in the in vitro assay,which matched the requirements as plant activators.

Approach to synthesis of novel chiral 3-chloro-2(5H)- furanone and its application in asymmetric reactions

The synthetic method of the novel chiral synthon, 5-/-menthyloxy-3-chloro-2-(5H)-furanone 5a and its application in asymmetric reactions were investigated. 5a is easily obtained in highly optical purity, and acts as a stable acceptor of Michael addition with oxygen nucleophiles in tandem double Michael addition / internal nucieophilic substitution to offer the spiro-cyclopropane derivative containing four stereogenic centers 8, which it is difficult to obtain by routine methods. The synthetic methods for 5a and 8 are reported in detail and the new compounds are identified on the basis of their analytical data and spectroscopic data, such as UV, IR, H NMR,13 C NMR, MS and elementary analysis. The absolute configuration of the interesting spiro-cyclopropanes, spiro [1-chloro-4-(/-menthyloxy)-5-oxo-6-oxa-biscyclo[3.1.0]hexane-2,3i(4’-/-menthyloxy-5’-/-menthyloxy- butyrolactone)] 8 was established by X-ray crystallography. This result can provide important synthetic strategy in synthesis of some complex

A Facile Synthesis of Enantiomerically Pure （R）-6-Arylbinols

This work reported a convenient method for the preparation of enantiomerically pure 6-aryl-2,2＇-dihydroxy-1, l＇- binaphthyl derivatives starting from the commercially available （R）-2,2＇-hydroxy-l, l＇-binaphthyl [（R）-I] via bromi- nation, hydrolysis and Suzuki cross coupling reaction. This novel synthetie method was characterized with high re- gioselectivity, simple operation, mild reaction conditions, and excellent yield （up to 73%）. On the other hand, we synthesized the target unknown compounds, which were confirmed by IR, 1H NMR, 13C NMR, MS and elementary analysis.