Preparation of 3,4-Dihydro-2H-pyran Catalyzed by Modified Gamma Alumina

A promising catalytic material, modified ga mma alumina with high surface area (300m2/g) and higher c ontents of strong acid sites was developed. It was prepared by a special precip itation method with aluminum nitrate solution containing a certain amounts of or thosilicic acid and ammonia aqueous solution. Compared with commercial gamma alu mina, the modified gamma alumina is an effective catalyst for dehydration of tet rahydrofurfuryl alcohol to 3,4-Dihydro-2H-pyran.Under the optimized reaction conditions, an improved yield of 3,4-Dihydro-2H-pyran of 93.4% was achieved. The profiles of pyridine TPD show that the modified gamma alumina exhibits more strong acid sites than that in the commercial gamma alumina, indicating the stro ng acid sites on the surface of the catalyst may play a crucial role in this rea ction.

Reaction of 5-trifluoroacetyl-3,4-dihydro-2H-pyrane with Zinc Agents

A one pot reaction of 5-trifluoroacetyl-3,4-dihydro-2H-pryane with alkyl bromide RBr in the presence of zinc powder gave corresponding alcohol (CH2)3OCH=C(R)C(CF3)OH (R:CH2=CHCH2-, 3a; CH2CO2Me 3b), 3b are readily hydrolysed to corresponding carboxylic acid under dilute acidic condition, intramolecular cycle addition of this acid afforded bicyclo lactone. Treatment of 5 with pyridine and POCl3 to afford product dehydroration by the trifluoromethyl substituted α,β-unsaturated carbonyl compound 6.4- Trifluoroacetyl 2,3-dihydro-2H-furan behaves similar compounds 8, 9 and 10 are prepared.

Synthesis of 1-aryl-3-(3,4-dihydro-2H-chromen-5-yl) ureas as TNF-αinhibitors

A new series of compounds, 1-aryl-3-（3,4-dihydro-2H-chromen-5-yl） ureas, have been synthesized and their structures were confirmed by FAB-MS and IH NMR. The preliminary pharmacological screening showed that these compounds inhibited TNF-α production in lipopolysaccharide （LPS）-stimulated THP-1 cells.

Synthesis and Crystal Structure of Ethyl 3-(4-Chlorophenyl)-3,4-dihydro-6-methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate

The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215（9）, b = 8.5311（4）, c = 21.6886（9） A^°, β = 91.607（1）°, V = 3814.0（3）A^°^3, Z = 8, Dc = 1.400 g/cm^3, F（000） = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.

Vasorelaxant effect of 3,4-dihydro-2-(4-morpholinylmethy)-1(2H)-naphthalenone on the vascular smooth muscle of rabbits

The purpose of this study was to examine the relaxation effect of CY on the vascular smooth muscle （VSM） from rabbits. Experiments were carried out on isolated thoracic aorta of rabbits. CY （3 x 103 mM- 3 mM） could relax the VSM preparations pre-contracted by adrenaline （AD）, noradrenaline （NE）, high-K^＋ solution or BaCl2 with respective EC50 values of （0.3 1±0.11） mM, 0.19±0.03 mM, 0.20±0.04 mM and 0.25±0.04 mM. Moreover, CY （10-2 mM, 0.1 mM and 1 mM） inhibited norepinephrine （NE）, CaCl2 and KCl-induced vasoconstriction in a concentration dependent manner. The phasic contraction produced by NE was concentration dependently attenuated with CY （10^-2 mM, 0.1 mM and 1 mM） in calcium-free medium, similar to that caused by verapamil. The present findings suggest that CY relaxed thoracic aortic rings by blocking voltage-dependent Ca^2＋ channels. The inhibition of intracellular Ca^2＋ release may be one of the main vasorelaxant mechanisms of CY.

Sensitized photooxygenation^+——VI. Kinetic studies on the singlet oxygenation of 6-ethyl-3,4-dihydro-2H-pyran-5-carboxylic acid ethyl ester and 6-isopropyl-3,4-dihydro-2H-pyran-5-carboxylic acid ethyl ester

Kinetic studies of the singlet oxygenation of the title compounds were performed accord- ing to Monroe's method. The reaction rate increases with temperature decreasing, leading to a ne- gative activation enthalpy and a large negative activation entropy. These data are interpreted as the evidence for the intermediacy of an exciplex. The solvent effect on the reaction rate suggests that the “dioxetane” path involves a transition state or an intermediate with significant zwitterionic character. The electronic effect of the substituent is obvious, with electron-withdrawing substituent retarding the reaction and electron-donating substituent increasing the reaction rate. However, steric bulkiness at the 6-position does not play an important role in the reaction rate.

Oxidative C—H alkynylation of 3,6-dihydro-2H-pyrans

Current synthesis of α-substituted 3,6-dihydro-2H-pyrans dominantly relies on functional group transformation. Herein, a direct and practical oxidative C -H alkynylation and alkenylation of 3,6-dihydro-2H-pyran skeletons with a range of potassium trifluoroborates is developed. The metal-free process is well tolerated with a wide variety of 3,6-dihydro-2H-pyrans, rapidly providing a library of 2,4-disubstituted 3,6-dihydro-2H-pyrans with diverse patterns of α-functionalities for further diversification and bioactive small molecule identification.

Design and Synthesis of Novel 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides-based Strobilurins as Potent Fungicide Candidates

To discover novel strobilurins analogues with good and broad spectrum activity,a series of nove 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides-based strobilurins was designed,synthesized,and tested agains various phytopathogenic fungi.Compounds 7b.7c.and 7k exhibited substantial and broad spectrum antifungal activities against the tested phytopathogenic fungi,especially compound 7b,which showed 100%,80%,90%,and 90%antifungal activity(in virto)against Erysiphe graminis(E.graminis),Puccinia sorghi Schw:(P sorghi Schw.)Colletotrichum lagenarium(C.lagenarium),and Pseudoperonospora cubensis(P cubensis)at 300 ug/mL,respectively.better or comparable to the positive control azoxystrobin.Moreover,compound 7b exhibited 85%greenhouse inhibi.tion activity(in vivo)against E.graminis even at 0.2μg/mL,equal to azoxystrobin(90%)and trifloxystrobin(90%)Meanwhile,compound 7b against P cubensis displayed 70%and 55%greenhouse inhibition activity(in vivo)at 1.56 and 0.2μg/mL,respectively,much better than those of azoxystrobin and trifloxystrobin(both 0%at 1.56 and 0.2 ug/mL).Therefore,compound 7b could be considered as the most promising fungicidal candidate for furthe study.Furthermore,based on the effective concentration(ECso)against C.arachidicola,the built CoMSIA model provided the useful reference for the further structural optimization design.

不对称双酸催化3,4-二氢-2H-吡喃的反电子Hetero-Diels-Alder反应

研究了双酸催化剂不对称催化烯醚和β,γ-不饱和α-酮酸酯的反电子Hetero-Diels-Alder(HDA)反应,为手性合成3,4-二氢-2H-吡喃类化合物提供了一种新的催化合成方法.InBr3与手性磷酸钙盐Ca(1c)2组合的手性双路易斯酸催化体系能够有效催化3,4-二氢-2H-吡喃和β,γ-不饱和α-酮酸酯的反电子HDA反应,反应给出优秀的产率(最高达98%),中等到良好的非对映选择性(最高达89∶11)和良好到优秀的对映选择性(最高可达94%).并且该双酸催化体系也能成功实现其它烯醚(如:2,3-二氢-2H-呋喃,乙烯基乙醚)的HDA反应,获得优秀的非对映选择性(>94∶6)和良好的对映选择性.

A benzoxazine derivative specifically inhibits cell cycle progression in p53-wild type pulmonary adenocarcinoma cells

A fundamental aspect of cancer development is cancer cell proliferation.Seeking for chemical agents that can interfere with cancer cell growth has been of great interest over the years.In our study,we found that a benzoxazine derivative,(6-tert-butyl-3,4-dihydro-2Hbenzo[b][1,4]oxazin-3-yl)methanol(TBM),could inhibit cell growth and caused significant cell cycle arrest in pulmonary adenocarcinoma A549 and H460 cells with wild-type p53,while not affecting the cell cycle distribution in p53-deleted H1299 lung adenocarcinoma cells.Since P53 plays an important role in regulating cell cycle progression,we analyzed the protein level of p53 by Western blot,and detected a significant elevation of p53 level after TBM treatment in A549 and H460 cells.The data suggested that TBM might specifically inhibit the proliferation of p53 wild-type lung adenocarcinoma cells through a p53-dependent cell cycle control pathway.More interestingly,results indicated that TBM might serve as a useful tool for studying the molecular mechanisms of lung cancer cell growth and cell cycle control,especially for the biologic process regulated by P53.

Poly （ADP-ribose） polymerase inhibitor reduces heart ischaemia/ reperfusion injury via inflammation and Akt signalling in rats

Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoquinolinone （DPQ）, a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms. Methods Studies were performed with I/R rats＇ hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB （NF-KB）, intercellular adhesion molecule-1 （ICAM-1）, cyclooxygenase-2 （COX-2） and matrix metalloproteinase-9 （MMP-9） were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-313 （GSK- 3β） and forkhead transcription factor FOXO3a. Results Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from （35±5）% to （20±4）% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-KB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a. Conclusion The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly （ADP-ribose） polymerase reduced heart I/R injury in rats.