Ga(ClO_4)_3-catalyzed Reaction of 1,2-Diamines and α-Bromoketones:Synthesis of 2-Substituted Quinoxalines

Ga（ClO4）3-catalyzed reaction of 1,2-aryldiamines and α-bromoketones to afford 2-substituted quinoxalines in good yields is described.The reaction proceeded via grinding process with 10%（molar fraction） catalyst under solvent-free conditions at room temperature.For unsymmetrical o-phenylenediamines bearing electron-withdrawing groups,regio-selective quinoxalines were obtained.

3D-QSAR Studies on 3-Substituted N-Benzhydryl-nortropane Analogs as Nociception Receptor Agonists

The nociceptin receptor（NOP） has been involved in multiple biological functions, including pain, anxiety, cough, substance abuse, cardiovascular control, and immunity. Thus, selective NOP agonists might have clinical potential for the treatment of related diseases. In the present work, three-dimensional quantitative structure-activity relationship（3D-QSAR） studies were performed on a series of 3-substituted N-benzhydryl-nortropane analogs as NOP agonists using comparative molecular field analysis（Co MFA） and comparative molecular similarity indices analysis（CoM SIA） techniques. The statistically significant models were obtained with 54 compounds in training set by ligand-based atom-by-atom matching alignment. The CoM FA model gave cross-validated coefficient（q2） value of 0.530 using 6 components, non-cross-validated（r2） value of 0.921 with estimated F value of 93.668, and standard error of estimate（SEE） of 0.185. The best Co MSIA model resulted in q2 = 0.592, r2 = 0.945, N = 10, SEE = 0.162, and F = 75.654, based on steric, electrostatic, hydrophobic and hydrogen bond acceptor fields. The predictive ability of the Co MFA and CoM SIA models was further validated using a test set of 18 molecules that were not included in the training set, which resulted in predictive correlation coefficients（r2pred） of 0.551 and 0.637, respectively. Moreover, the CoM FA and CoM SIA contour maps identified the features important for exhibiting potent binding affinities on NOP, and can thus serve as a useful guide for the design of potential NOP agonists.

CRYSTALLINE MORPHOLOGY IN A SERIES OF CH_(3)-SUBSTITUTED THERMOTROPIC AROMATIC POLYESTERS WITH EVEN AND ODD FLEXIBLE SPACERS

Crystalline morphology in a series of CH_(3)-substituted main chain thermotropic aromatic polyesters with even and odd numbered methylene spacers has been studied by polarizing optical microscopy(POM),scanning electron microscopy(SEM)and transmission electron microscopy(TEM).On crystallization from solution evaporation spherulites of radial structure were observed in the polymers with even numbered spacers,but spherulites with concentric rings form in the polymer with odd numbered spacers.Both spherulites have a lamellar structure,which is about 10 nm in thickness.On crystallization from nematic glassy state spherulites can not be grown;lamellar structure was only observed around disclinations in a specimen during crystallization.Ln the case of crystallization from nematic melt two types of spherulites can be observed far the sample with even numbered spacers.For the sample with add numbered spacers spherulites can not be formed,but only irregular crystallites.

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS 69.A NOVEL SYNTHESIS OF 5-SUBSTITUTED 3-(1'-DIETHOXYPHOSPHORYLALKYL)-2-ISOXAZOLINES

Additions of diethyl phosphite to α-nitroalkenes followed by the introduction of trimethylchlorosilane and an activated alkene, gave the corresponding title compounds via regioselective 1,3-dipolar cycloaddition in moderate yield.

吡啶叶立德与查尔酮1,3-偶极环加成反应制备2-苯基-3-乙酰基中氮茚

报道在氧化剂存在下吡啶叶立德与查尔酮进行1,3-偶极环加成反应,一锅法合成2-苯基-3-乙酰基中氮茚化合物的方法,收率37％．用类似的方法由α-溴代异喹啉季铵盐、查尔酮、碱和氧化剂进行反应,可一锅法得到1-苯甲酰基-2-苯基-3-乙酰基吡咯并[2,1-α]异喹啉,收率58％．

N-异喹啉-3-羧酸-L-亮氨酸苄酯抗人食道癌作用的研究

目的:体内外研究N-异喹啉-3-羧酸-L-亮氨酸苄酯(N-isoquinoline-3-carbonyl-L-Leucinebenzylester,IQ-L-OBzl)对人食道癌细胞体抗肿瘤作用。方法:MTT法检测细胞活性;检测食管癌裸鼠移植瘤模型的瘤重,计算抑瘤率及外周血白细胞数;流式细胞仪检测细胞内活性氧(intracellular reactive oxygen species,ROS)的水平。结果:在体外实验中IQ-L-OBzl组的食管癌(Eca-109、EC-9706)IC50分别为(405.06±23.49)nmol/L、(485.79±48.47)nmol/L;体内实验中最高抑瘤率为(42.42±7.47)%,化合物的抑瘤率及瘤重有明显的浓度相关性;IQ-L-OBzl组细胞内ROS水平为(98.68±13.19)平均荧光强度(MFI),高于对照组(P<0.05)。结论:IQL-OBzl的体内、外抗食道癌作用与细胞内ROS有关,且对白细胞无明显毒副作用。

Cu(OAc)_(2)-Mediated Synthesis of Fullerodihydropyridine-3-ones via the Reaction of[60]Fullerene with β-Substituted Ethylamines in the Absence or Presence of Arylacetaldehydes

A series of unreported fullerodihydropyridine-3-ones were synthesized as a new family of fullerene derivatives in moderate to good yields by a simple one-step reaction of[60]fullerene with cheap and readily available β-substituted ethylamines in the absence or presence of arylacetaldehydes under the assistance of Cu(OAc)_(2).The in situ generation of arylacetaldehydes by the C—N bond cleavage of arylethylamines avoided their complex synthesis in advance and realized the preparation of fullerodihydropyridine-3-ones with structural and functional diversities,which may have promising applications in perovskite solar cells to improve the performance of photovoltaic devices due to the existence of a largeπ-conjugated system on the dihydropyridine-3-one ring.

手性流动相添加剂-HPLC法拆分6,7-二甲氧基-1,2,3,4-四氢-异喹啉-3-羧酸

以L-苯丙氨酸为手性添加剂,硫酸铜为络合剂,用常规的反相高效液相色谱法拆分6,7-二甲氧基-1,2,3,4-四氢-异喹啉-3-羧酸。并研究了L-苯丙氨酸与Cu2+的配比、流动相pH和甲醇比例、柱温等因素对该对映体保留特性和分离度的影响。

光催化烯烃加成/环化合成含氟异喹啉-1,3-二酮

发展了一种光催化活泼烯烃加成/环化合成含氟异喹啉-1,3-二酮的反应.在可见光催化下,多种N-烷基-N-甲基丙烯酰基苯甲酰胺衍生物与全氟碘代丁烷、溴二氟乙酸乙酯发生自由基串联加成环化反应,以67%~80%的产率合成了一系列具有潜在生理活性的含氟取代异喹啉-1,3-二酮衍生物.这为具有潜在药用价值的氟取代异喹啉-1,3-二酮的合成提供了一条绿色、高效、条件温和的途径.

β-环糊精和3-羧基四氢异喹啉包合物的核磁共振研究

利用高分辨液体核磁共振技术,研究β-环糊精(β-CD)能否与3-羧基四氢异喹啉(THIQA)相互作用形成包合物从而改善后者溶解度.通过高分辨率利用1 H NMR及2DROESY技术观察β-CD和THIQA作用前后的谱图.结果从高分辨核磁的1 H NMR及2DROESY可以清晰地看出THIQA和β-CD可以形成包合物;THIQA能够进入β-CD的疏水空腔并发生相互作用,并且主要与β-CD空腔内部的质子H5以及窄口端H6相互作用.

苯甲酸催化的三组分[3+2]环加成反应合成六氢吡咯并[2,1-a]异喹啉化合物

发展了一种合成六氢吡咯并[2,1-a]异喹啉化合物的新方案,以苯甲酸为催化剂,4?分子筛为添加剂,催化芳香醛、1,2,3,4-四氢异喹啉和N-取代马来酰亚胺经串联的醛胺缩合和[3+2]环加成反应,合成了一系列六氢吡咯并[2,1-a]异喹啉化合物。主要考察了催化剂、溶剂、反应时间及反应温度对产物产率的影响,最终确定在60℃下,以10 mL超干甲苯为溶剂,20 mol%苯甲酸为催化剂,加入250 mg分子筛,以n(芳香醛)∶n(1,2,3,4-四氢异喹啉)∶n(N-取代马来酰亚胺)=1∶1.3∶1.2反应2 h。产物结构经;HNMR、;CNMR和HRMS等手段表征,产物(8R,8aR,11aS,11bR)-8-(2-氯苯基)-10-甲基-5,6,8,8a,11a,11b-六氢-9H-吡咯并[3′,4′∶3,4]吡咯并[2,1-a]异喹啉-9,11(10H)-二酮空间立体结构由单晶X射线衍射确定。

N-叔丁基(4aS,8aS)-十氢异喹啉-3(S)-甲酰胺的合成及结构表征

以L-苯丙氨酸为原料制备N-叔丁基-1,2,3,4四-氢异喹啉-3(S)甲-酰胺(T ICC),后者经铑/氧化铝催化加氢制备N-叔丁基(4aS,8aS)十-氢异喹啉-3(S)甲-酰胺(DH IQ)。1H-NMR、M S确定产物的化学结构;GC-M S分析产物中的异构体;单晶X射线衍射确定DH IQ的绝对构型;旋光度的测定表明DH IQ产物的光学纯度达到了98%。

Reactivity of 1-methylisoquinoline synthesis of pyrazolyl triazoloisoquinoline and thia-diazolyl isoquinoline derivatives

The reaction of 1-methylisoquinoline 1 with hy-drazonoyl halides 2 in ethanol in the presence of chitosan under microwave irradiation affords triazoloisoquinoline 4. Product 4 reacts with dimethylformamide-dimethylacetal to give ena- minones 7 which react with hydrazonoyl halides to give pyrazolyl triazoloisoquinoline 13. Also, 1-methylisoquinoline 1 reacts with arylisothio-cyanate to give thioanilide 15 which reacts with hydrazonoyl halides to give the corresponding thiadiazolyl isoquinoline derivatives 20, 24.

Crystal Structure of Isoquinoline Derivatives

The chiral compound 5H-imidazol[2,3-b]isoquinoline-l-ethanol-5-one-1,2, 3, 10b-tetrahydro- β（S）-phenyl-3（S）-phenyl was synthesized from the direct condensation of 2- cyanophenyacetonitrile with optically active （S）-（＋）-2-phenylglycinol in chlorobenzene under dry, anaerobic conditions. ZnCl2 was used as a Lewis acid catalyst in this reaction, and the structure of this compound was determined by X-ray diffraction, NMR, MS and IR. Crystal data of the title compound： C25H22N2O2, Mr = 382.45, P 21 21 21, a = 5.341（5）, b = 16.735（5）, c = 22.129（5） A, γ = 90°, V = 1978（2）A^3, Z = 4, Dc = 1.284 g/cm^3, the final R = 0.0321 for 2269 observed reflections with I 〉 2 σ（I） and Rw = 0.0771 for all data.

Boosting Li-ion storage in Li2MnO_(3) by unequal-valent Ti4+-substitution and interlayer Li vacancies building

Lithium rich layered oxide(LRLO) has been considered as one of the promising cathodes for lithium-ion batteries(LIBs). The high voltage and large capacity of LRLO depend on Li2MnO_(3)phase. To ameliorate the electrochemical performance of Li2MnO_(3), also written as Li(Li1/3Mn2/3)O_(2), we propose a strategy to substitute Mn4+and Li+in Mn/Li transition metal layer with Ti4+, which can stabilize the structure of Li2MnO_(3)by inhibiting the excessive oxidation of O_(2)-above 4.5 V. More significantly, the unequal-valent substitution brings about the emergence of interlayer Li vacancies, which can promote the Li-ion diffusion based on the enlarged interlayer and increase the capacity by activating the Mn3+/4+redox. We designed Li0.7[Li1/3Mn2/3]0.7Ti0.3O_(2)with high interlayer Li vacancies, which presents a high capacity(290 m Ah/g at 10 m A/g) and stable cycling performance(84% over 60 cycles at 50 m A/g). We predict that this strategy will be helpful to further improve the electrochemical performance of LRLOs.

An effcient one-pot multi-component synthesis of 3,4,5-substituted furan-2(5H)-ones catalyzed by tetra-n-butylammonium bisulfate

A facile one-pot synthesis of 3,4,5-substituted furan-2（5H）-one derivatives from a three-component reaction of aniline derivatives, dialkylacetylenedicarboxylates and aromatic aldehydes under mild conditions using tetra-n-butylammonium bisulfate as a catalyst has been developed.

Study on the Biological Activity of 3-Aroyl-5-substituted Thiophene Derivatives Based on the CoMFA Method

A three-dimensional quantitative structure-activity relationship(3 D-QSAR) study was conducted to analyze the A1 AR density(Bmax) of 56 3-aroyl-5-substituted thiophene derivatives(ASTDs) in human A1 Chinese hamster ovary(hA1 CHO) membranes by the comparative molecular field analysis(CoMFA) method. A training set of 45 compounds was used to establish the predictive model, which was verified by the test set of 17 compounds containing template molecule and 5 newly designed molecules. The cross-validation(R2 cv) and non-cross-validation(R2) coefficients of the training set were 0.655 and 0.959, respectively. The model was used to predict the activities of the compounds of the training and test sets, and the results indicated that the models had strong stability and good prediction ability. According to model analysis, the contribution of steric and electrostatic fields was 51.4% and 48.6%, respectively. Based on the 3 D contour maps, five excellent ASTDs agonists were designed, which need to be further verified by biomedical experiments.

[4+1]Annulation of in situ generated azoalkenes with amines:A powerful approach to access 1-substituted 1,2,3-triazoles

1-Substituted 1,2,3-triazoles represents‘privileged’structural scaffolds of many clinical pharmaceuticals.However,the traditional methods for their preparation mainly rely on thermal[3+2]cycloaddition of potentially dangerous acetylene and azides.Here we report a base-mediated[4+1]annulation of azoalkenes generated in situ from readily available difluoroacetaldehyde N-tosylhydrazones(DFHZ-Ts)with amines under relatively mild conditions.This azide-and acetylene-free strategy provides facile access to diverse 1-substituted 1,2,3-triazole derivatives in high yield in a regiospecific manner.This transformation has great functional group tolerance and can suit a broad substrate scope.Furthermore,the application of this novel methodology in the gram-scale synthesis of an antibiotic drug PH-027 and in the late-stage derivatization of several bioactive small molecules and clinical drugs demonstrated its generality,practicability and applicability.

Synthesis of 4-substituted 3-oxabicyclo[3.1.0]hexan-2-one

Cyclopropanedicarboxylic acid anhydride can be converted to 4-substituted 3-oxabicyclo- [3.1.0]hexan-2-one by reaction with Grignard reagents in ether or tetrahydrofuran solution.