Discovery and structure-activity relationship studies of novel tetrahydro-β-carboline derivatives as apoptosis initiators for treating bacterial infections

Developing and excavating new agrochemicals with highly active and safe is an important tactic for protecting crop health and food safety.In this paper,to discover the new bactericide candidates,we designed,prepared a new type of1,2,3,4-tetrahydro-β-carboline(THC)derivatives and evaluated the in vitro and in vivo bioactivities against the Xanthomonas oryzae pv.oryzae(Xoo),Xanthomonas axonopodis pv.citri(Xac),and Pseudomonas syringae pv.actinidiae(Psa).The in vitro bioassay results exhibited that most title molecules possessed good activity toward the three plant pathogenic bacteria,the compound A17 showed the most active against Xoo and Xac with EC50 values of 7.27 and 4.89 mg mL^(-1)respectively,and compound A8 exhibited the best inhibitory activity against Psa with EC50value of 4.87 mg mL^(-1).Pot experiments showed that compound A17 exhibited excellent in vivo antibacterial activities to manage rice bacterial leaf blight and citrus bacterial canker,with protective efficiencies of 52.67 and 79.79%at 200 mgmL^(-1),respectively.Meanwhile,compound A8 showed good control efficiency(84.31%)against kiwifruit bacterial canker at 200 mg mL^(-1).Antibacterial mechanism suggested that these compounds could interfere with the balance of the redox system,damage the cell membrane,and induce the apoptosis of Xoo cells.Taken together,our study revealed that tetrahydro-β-carboline derivatives could be a promising candidate model for novel broadspectrum bactericides.

A New β-Carboline Alkaloid and a New Derivate of Isoferulic Acid from Anemone altaica

A new β-carboline alkaloid, 4-（9H-β-carbolin-1-yl）-4-oxobutyric acid and a new derivate of isoferulic acid, （E）-3-（3-hydroxy-4-methoxyphenyl）acrylic acid carboxymethyl ester, were isolated from the roots of Anemone altaica. Their structures were determined on the basis of spectral data.

β-Carboline alkaloids from Trigonostemon filipes and Trigonostemon lii

Sixβ-carboline alkaloids including three new ones,trifilines A-C(1-3)were isolated from Trigonostemon filipes,along with a newβ-carboline alkaloid,trigonoine C(7)isolated from Trigonostemon lii.Their structures were elucidated by extensive spectroscopic techniques.Trifilines A(1)and B(2)showed weak anti-HIV-1 activity with EC50 values of 54.61μg/mL and 9.75μg/mL,along with TI(Therapeutic index)values of 1.52 and 1.42,respectively.This is the first time to report the chemical constituents of Trigonostemon filipes.

Solid Phase Synthesis of β-Carbolines

Synthesis of β-carbolines on solid phase using TCCA as the key reagent is developed.

Chiral Ligands from Abrine.4. Heterocycle-Containing 1,2,3,4-Tetrahydro-β-Carboline Methyl Ester Used for Catalysis of Enantioselective Addition of Diethylzinc to Benzaldehyde

Four 1, 2,3,4-tetrahydro - β - c arboline amino acid esters with a heterocycle at the C- 1position were used as chiral ligands in the enantioselective addition reactions. The differentpositions of the heteroatoms gave different effects, and medium but opposite enantioselectivitywas recorded.

Synthesis, Characterization and X-ray Crystal Structure of 2-Benzyl-7-butoxyl-9-isobutyl-1-methyl-β-carboline Bromide

2-Benzyl-7-butoxyl-9-isobutyl-1-methyl-β-carboline bromide（H-2-65） was synthesized by the reaction of Harmine with 1-iodobutane via N9-alkylation, demethyl and N2-quaternarization to obtain the new compound. The results demonstrate that H-2-65 has more remarkable anticancer activities in vitro. The results of 1H NMR, 13 C NMR, DEPT, g COSY, g HSQC, g HMBC, MS, single-crystal X-ray diffraction and elemental analysis showed that the title compound crystallizes in the triclinic system, space group P1 with a = 9.545（5）, b = 11.724（5）, c = 11.839（6） , α = 77.530（6）, β = 87.169（6）, γ = 72.823（5）o, Z = 2, V = 1235.8（10）3, Dc = 1.294 g·cm-3, F（000） = 504, the final R = 0.0453, wR = 0.1262 and S = 1.044.

Total synthesis of bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane as potent PTP1B inhibitor

Protein tyrosine phosphatase 1B （PTP1B） plays an important role as a negative regulator and has been proved to be an effective target for the treatment of type 2 diabetes mellitus. Bis-（2,3-dibromo-4,5-dihydroxyphenyl）-methane 7 was first reported as a natural bromophenol with significant inhibition against PTP1B which was isolated from red algae Rhodomela conrervoides. Intrigued by its astonishing activity （IC50 = 2.4 μmol/L）, compound 7 was synthesized with the overall yield of 24% and evaluated for its PTPIB inhibitory activity compared with natural compound.

Solubility determination and thermodynamic modeling of bis-2-hydroxyethyl terephthalate(BHET)in different solvents

Studies on the degradation process of waste polyethylene terephthalate(PET)have become increasingly mature,but there are relatively few studies on the separation of degradation products.The products contain many components and the separation of which is difficult.Therefore,the study on phase equilibrium thermodynamics of bis-2-hydroxyethyl terephthalate(BHET)is of great theoretical significance and practical value to provide basic data for the BHET crystallization separation.In this work,the degraded products were purified and characterized.The solubility of BHET in methanol,ethanol,ethylene glycol,water and the mixture of ethylene glycol+water were determined by static method.The experimental results were correlated with different models,such as ideal solution(IS)model,λh equation,Apelblat equation and NRTL model.Based on the van’t Hoff equation,the mixing Gibbs energy,enthalpy and entropy were calculated.From this work,the basic data which can be used to guide the crystallization process of BHET were obtained,including solubility data,correlation model and thermodynamic properties.

Oxalic acid as a catalyst for efficient synthesis of bis-(indolyl)methanes,and 14-aryl-14H-dibenzo[a,j]xanthenes in water

A simple, efficient, and environment benign route was developed for the preparation of bis-（indolyl）methanes and 14-aryl-14H- dibenzo[aj]xanthenes from condensation of various aromatic aldehydes or ketones with indole, and 2-naphthol, respectively, using oxalic acid catalyst in aqueous medium. Use of cheap and easily available catalyst, better yields and simple reaction protocol are the advantages of the present method.

New Greener Alternative for Biocondensation of Aldehydes and Indoles Using Lemon Juice: Formation of Bis-, Tris-, and Tetraindoles

This work presents a new greener alternative for biocondensation of aldehydes and indoles for the synthesis of bis- and tris(indolyl)methanes catalyzed by lemon juice (Citrus limon) in good yields under ultrasound irradiation in aqueous ethanol. Various substituted aldehydes with indoles under this reaction condition are elucidated. Also, tetraindolyl compounds were prepared using terephthaldialdehyde by following the same protocol. This method is an environmentally benign, efficient reaction, which requires shorter reaction time and simple experimental and work-up procedures.

Synthesis of some new bis-3,4-dihydropyrimidin-2(1H)-ones by using silica-supported tin chloride and titanium tetrachloride

Silica-supported tin chloride and titanium tetrachloride were prepared by the reaction of tin chloride and titanium tetrachloride with activated silica gel in refluxing toluene.These solid acids have been employed as the catalysts for the synthesis of bisdihydropyrimidin -2(1H)-ones from aromatic dialdehydes,1,3-dicarbonyl compounds and urea at 90℃under solvent-free conditions.

Synthesis and Crystal Structure of the Intermediate Bis-9-fluorenylmethylphenyl Silane

The title compound bis-9-fluorenylmethylphenyl silane (C33H26Si, Mr = 450.63) was synthesized and its structure has been synthesized and determined by X-ray analysis. The crystal is of triclinic, space group P with a = 9.478(1), b = 10.0956(1), c = 13.0243(2) ? a = 92.668(2), b = 90.809(2), g = 99.348(2)? l = 0.71073 ?, m(MoKa) = 0.115 mm-1, V = 1288.1(2) 3, Z = 2, Dc = 1.219 g/cm3 and F(000) = 476. The structure was refined to R = 0.0437 and wR(F2) = 0.0963 for 3346 observed reflections with I>2s(I). X-ray diffraction analysis reveals that the title compound is bis-9-fluorenylmethylphenyl silane.

Gold （III） Complexes with Thiolactate and bis-（1,4-Sodiumthiolactate） Butane Ligands

The new ligand bis-（1,4-sodium thiolactate） butane （L）-O2CCH3S-（CH2）4SCHCH3CO2- has been prepared from the reaction of disodium salt of thiolactic acid and 1,4-dichlorobutane, while the disodium thiolactate was prepared instanteously through the reaction of thiolactic acid with NaOH. Mono and dinuclear complexes were obtained by direct reaction of the above ligands with H[AuCI4] in 1 ： 1, 2：1, 1：2, 2：2 and 3：1 ligands to metal molar ratio. The prepared complexes were characterized by elemental analysis, spectral studies FTIR （Fourier transform Infrared） and UV-Vis, magnetic measurement, conductivity measurement and IHNMR for the ligand （L） and some of the complexes. The conductance data indicate that the complexes of the formulas Na[Au（SCH3CHCOO）2], Na[Au（SCH3CHCOO）（OOCCHCH3SH）2] and [Au（L）]Cl are 1：1 electrolyte. Electronic spectra and magnetic moment values indicate the presence of square planner geometry around Au（III） ions.

A New Compound with C_2-Symmetry 3R,3'R-Dihydroxy-6,6',6,6'-tetramethyl-2R,2'R,-bis-4H-pyran

The title compound 1 was synthesized from 1.2:5,6-dianhydro-3,4-dianhydro-3,4-isopropylideneD-mannitol 2 through four steps in a total yield of 53%. The absolute configuration of this compound was confirmed by X-ray diffraction.

BIS-丙泊酚闭环靶控输注全静脉麻醉在消化道肿瘤切除手术中的应用效果

研究BIS-丙泊酚闭环靶控输注全静脉麻醉在消化道肿瘤切除手术中的应用效果。方法 从2019年4月到2020年8月,本院收治的98例消化道肿瘤患者中,按照随机数字表法,将这98例患者分成两组,一组是观察组(n=49),另一组是对照组(n=49),观察组,给予异丙酚闭环靶控输注全静脉麻醉,对照组给予丙泊酚开环靶控输注全静脉麻醉,并进行10周的观察。观察两组患者在不同时间点的血液动力学指标, BIS值,丙泊酚血药浓度,麻醉恢复,术后并发症,术中知识等方面的差别。结果 两组间 MAP和 HR值无显著性差异(P>0.05);在T9时点,观察组 BIS值明显高于对照组(P<0.05),而在其它时点,两组 BIS值无显著性差异(P>0.05);观察组的睁眼时间、气管拔管时间和方向恢复时间均显著小于对照组,有显著性差异(P<0.05);观察组、对照组两组患者术后并发症的发生率分别为8.16%和22.45%,有显著性差异(P<0.05)。结论 BIS-丙泊酚闭环靶控输注全静脉麻醉,可维持满意的麻醉深度,以BIS值为反馈更好控制丙泊酚血药浓度,促进麻醉后患者的恢复,降低术中知晓及术后并发症的发生。

Chemoselective synthesis of α-carboline derivatives via hypervalent iodine-catalyzed [3+3] annulation under metal-free conditions

A strategy for the synthesis ofα-carboline derivatives from indole-3-carboxaldehydes and 3-aminocyclohex-2-enones under metal-free conditions has been developed.The combination use of phenyliodine(Ⅲ)diacetate(PIDA)and benzoic acid could significantly facilitate the corresponding[3+3]annulation process.This newly developed strategy featured unextraordinary chemoselectivity,good functional group tolerance and the preservation of the carbonyl group of the ketone substrates,which offers the possibility for further transformation of the products.

β-Carboline alkaloids from the roots of Peganum harmala L.

This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala L.Among these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial chirality.Compound 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-carboline.The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations.The biosynthetic pathways of 1−3 were proposed.Additionally,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was evaluated.Notably,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),respectively.Furthermore,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).

硫脲基桥联双四苯乙烯有机荧光传感器的制备及在水介质中叶黄素检测上的应用

以4-羟基四苯乙烯与溴乙酸乙酯为起始原料设计并合成一种硫脲基桥联双四苯乙烯(Bis-S)有机荧光传感器。将Bis-S溶解在95%(体积分数)四氢呋喃溶液中制备Bis-S溶液,采用荧光光谱仪在激发波长360 nm、发射波长468 nm下测量叶黄素加入前后Bis-S体系的荧光强度。结果显示:在Bis-S溶液或含Bis-S的传感试纸中加入叶黄素,叶黄素与Bis-S按照物质的量比1∶1结合并被Bis-S空腔包裹,Bis-S体系亮蓝色荧光猝灭;在Bis-S溶液或含Bis-S的传感试纸中加入共存生物分子鸟嘌呤、色氨酸、果糖、胞嘧啶、腺嘌呤、胸腺嘧啶、维生素B1、维生素B2、淀粉、蔗糖、葡萄糖、咖啡因、脯氨酸后,Bis-S体系荧光强度无明显变化;在含叶黄素的Bis-S溶液中加入上述共存生物分子,体系荧光强度较未加入共存生物分子的变化不大,说明Bis-S传感器对于叶黄素具有良好的选择性和抗干扰性,且在比色法检测叶黄素方面具有一定应用前景。当Bis-S的浓度为1.00×10^(-5)mol·L^(-1)时,Bis-S体系荧光强度随叶黄素浓度的增加而减弱,检测范围为0~2.00×10^(-5)mol·L^(-1),线性定量检测范围为0~0.06μmol·L^(-1),检出限(2s/k)为1.21×10^(-9)mol·L^(-1);进行4个浓度水平的回收试验,叶黄素的回收率为94.0%~101%,测定值的相对标准偏差(n=6)为1.5%~4.1%。

Synthesis and evaluation of tetrahydro β-carboline derivatives as anticancer agents

A series of β-carboline derivatives （1–6） have been synthesized and evaluated for their anticancer activities. We observed that compound 5 exhibited significant anticancer activities over both human gastric cancer and human hepatic cancer cell lines, and compound 6, which is slightly different from 5 in its structure, showed good anticancer activity over human colorectal cancer cell line.

Efficient fixation of CO_(2) to cyclic carbonates and oxazolidinones with multi-hydroxyl bis-(quaternary ammonium) ionic liquids as catalysts under mild conditions

A series of multi-hydroxyl bis-(quaternary ammonium)ionic liquids(Ils1‒7)was prepared as bifunctional catalysts for the chemical fixation of CO_(2).All these ionic liquid compounds were efficient for the catalytic synthesis of cyclic carbonates and oxazolidinones via the cycloaddition reactions between CO_(2) and epoxides or aziridines with excellent yield and high selectivity in the absence of co-catalyst,metal and solvent.Due to the synergistic effects of hydroxyl groups and halogen anion,the cycloaddition reactions proceeded smoothly either at atmospheric pressure or room temperature.The selectivity for substituted oxazolidinones at 5-and 4-positions can be tuned via changing the reaction conditions.Finally,possible mechanisms including the activation of both CO_(2) and epoxide or aziridines were proposed based on the literatures and experimental results.