One-pot,green synthetic route for construction of coumarin C-4 bridged 2,6-dicyanoanilines and their photophysical study

A highly selective and more efficient green protocol has been developed via a one-pot, three-component approach for the synthesis of coumarin 2,6-dicyanoanilines in aqueous ethanol. From the mechanism, two molecules of malanonitrile condensed with aldehyde and ketone resulted in the adducts, which on intramolecular cyclization via two new C-C bonds formed to afford the title compound. The present methodology offers simplified purification and environmentally benign conditions, avoids the use of toxic solvents, and gives excellent yield with high purity. All the synthesized compounds have been characterized by spectral analysis. Optical and thermal screening studies of all newly synthesized compounds showed excellent photophysical and thermal stability properties.     

纺锤体驱动蛋白抑制剂的设计、合成与生物活性研究

纺锤体驱动蛋白(kinesin spindle protein, KSP/Eg5)作为潜在的肿瘤治疗靶点, 使发现KSP抑制剂成为热点. 设计并合成了4-氧基-β-四氢咔啉衍生物作为新型的KSP抑制剂, 并测定了其对KSP的抑制活性, 均优于阳性对照物. 其中化合物9c抑制KSP的IC50＝0.065 μmol•L－1, 优于阳性对照物Monastro l100多倍. 生物活性研究表明为抗肿瘤药物提供了新结构类型的候选化合物.     

Synthesis and fluorescent properties of a new class of heterocycles of isoindole fused imidazoles with phenolic subunits

A new class of heterocycles of isoindole fused imidazoles with phenolic subunits has been readily synthesized by a two-step one-pot reaction. In aprotic solvent they show high fluorescent properties (Phi(F) up to 0.93), but in protic polar solvent fluorescent intensity decreases. They show green fluorescence in weak acidic medium such as acetic acid but lack emission in basic medium. The compounds can also stain human squamous epithelium cells.     

Direct synthesis of polymacrocyclic boron compounds.: A convenient method for the synthesis of hemicarcerands

Six new hemicarcerand-like compounds have been synthesized via condensation reaction of 3-aminophenylboronic acid with 5,5′-methylene-bis(2-hydroxybenzencarbonyl) derivatives. The one-pot reaction constitutes an interesting approach to design molecular containers by direct synthesis in moderate yields. The strategy involves a self-assembly process through the formation of N-B coordinative bonds. The X-ray structural analysis for one derivative illustrates the inclusion of two benzene molecules within the cavity, showing in a first approximation the capability of the polymacrocyclic compounds to function as molecular receptors.     

Green one-pot synthesis of N -bisphosphonates as antimicrobial and antioxidant agents

A straightforward and greener approach has been developed for the synthesis of novel aminomethylene bisphosphonates by one-pot reaction of diverse aryl/heteroaryl amines with dialkyl phosphite and triethyl orthoformate using CuO nanoparticles as catalyst under microwave irradiation and solvent-free conditions. This is an ecofriendly synthetic approach for swift access to a library of diverse aminomethylene bisphosphonates. All the synthesized new compounds were evaluated for their antimicrobial activity by disc diffusion method and antioxidant activity by DPPH, H2O2, and NO methods. The title compounds exhibited significant antioxidant and considerable antimicrobial activities.     

p-TSA-catalyzed one-pot synthesis and docking studies of some 5H-indeno[1,2-b]quinoline-9,11(6H,10H)-dione derivatives as anticonvulsant agents

The present work describes a facile, one-pot three component environment friendly, green synthesis of a series of 5-(4-methoxyphenyl)-7,7-dimethyl-10-phenyl-7,8-dihydro-5H-indeno[1,2-b]quinoline-9,11(6H,10H)-dione derivatives 8(a-n). 1,3-indanedione, aryl-aldehyde and enaminone was thoroughly ground in the presence of catalytic amount of p-toluene sulfonic acid (p-TSA) to give the titled compounds in good yields. All the synthesized derivatives were evaluated for their anticonvulsant activity using the maximal electroshock (MES) method with phenytoin as a standard drug along with their neurotoxicity effect. Derivatives 8b, 8e and 8k exhibited significant anticonvulsant activity (P<0.001). The neurotoxicity study clearly revealed that all the tested compounds are non-toxic at a dose of 40 mg/kg. The molecular modeling studies also predicted good binding interactions of most active molecules with the serotonin 5-HT_2A receptor. Therefore, it can be safely concluded that synthesized derivatives 8(a-n) would represent useful leads for further investigation in the development of a new class of anticonvulsant agents.     

Synthesis and in vitro and in vivo antitumor/anticancer activity of novel O-Mannich bases of 4,6-diaryl-3,4-dihydropyrimidine-2(1H)-ones

A new series of [4,6 substituted diaryl-1,6-dihydropyrimidin-2-yl-oxymethyl]-amines 5a–o have been synthesized by the Mannich condensation on the respective 4,6-diaryl-3,4-dihydropyrimidine-2(1H)-ones 4, in basic medium using formaldehyde along with three secondary amines, viz., dimethylamine, piperidine and morpholine. The dihydropyrimidinones 4 in turn were synthesized by the cyclocondensation of chalcones 3 with urea. Alternatively, compounds 4 were also prepared directly by one-pot 3-component cyclocondensation reaction starting from acetophenone, benzaldehyde and urea. The structures of all the newly synthesized compounds have been confirmed by their spectral and analytical data. All the O-Mannich bases 5 have been evaluated for their in vitro cytotoxic and antitumor activities, and based on the results, the potent compounds were selected for in vivo activity, as well. Only one compound 5m of the series has been found to be relatively more effective.     

Catalyst-Free,One-Pot,Expeditious Synthesis of Aminoalkylnaphthols at Room Temperature

Aminoalkylnaphthols possess several biological and catalytic activities. A methodology has been developed for the multicomponent one-pot synthesis of aminoalkylnaphthols in dichloromethane under catalyst-free conditions at room temperature. The present approach possesses several advantages such as excellent yields, quick reaction time, mild reaction conditions, and very easy purification processes. Thirteen new compounds in addition to six known compounds have been synthesized by this methodology.     

AlCl3 induced C-arylation/cyclization in a single pot: a new route to benzofuran fused N-heterocycles of pharmacological interest

A new and one-pot synthesis of benzofuran fused N-heterocycles has been accomplished via AlCl₃-mediated C-C followed by C-O bond formation between 2,3-dichloropyrazine or its derivatives and phenols. The methodology provided novel compounds as potential inhibitors of PDE4B. The single crystal X-ray data of a synthesized benzofuran derivative are presented. Scope of the methodology, in vitro pharmacological data of some of the synthesized compounds, along with docking study of an active compound are described.     

Design and synthesis of novel N-benzylidenesulfonohydrazide inhibitors of MurC and MurD as potential antibacterial agents

A series of novel N-benzylidenesulfonohydrazide compounds were designed and synthesized as inhibitors of UDP-N-acetylmuramic acid: L-alanine ligase (MurC) and UDP-N-acetylmuramoyl-L-alanine: D-glutamate ligase (MurD) from E. coli, involved in the biosynthesis of bacterial cell-walls. Some compounds possessed inhibitory activity against both enzymes with IC(50) values as low as 30 microM. In addition, a new, one-pot synthesis of amidobenzaldehydes is reported.     

Synthesis and Molecular Structure of New Macro Acyclic Mannich Derivatives: Symmetrical and Unsymmetrical 2-[(E)-(Benzylideneamino)(aryl)methyl]cyclododecanone

Abstract

In an effort to provide a green synthetic route for heterocyclic scaffolds, new macro analogs of acyclic Mannich derivatives have been synthesized in good yields in a one-pot, efficient fashion. The acyclic symmetrical and unsymmetrical 2-[(E)-(benzylideneamino)(aryl)methyl]cyclododecanones have been synthesized by condensation of cyclododecanone, aromatic aldehyde, and ammonium acetate in ethanolic media. By infrared, NMR, and mass spectral analyses, their structures were determined. Examination of crystal structure of a p-Cl and o-Br analogs reveals the minimum energy [3333] square conformation of cyclododecanone ring. In the crystal, molecules aggregate in dimeric subunits formed by C-Cl … π and C-H..π interactions. The reported one-pot, multichain reaction of macrocycles is the first synthetic attempt of acyclic compounds in this type of Mannich reaction involving ketones containing active methylene groups.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

A facile synthesis of novel pyrrolo[3,4-<Emphasis Type="Italic">b</Emphasis>]quinolin-1-one derivatives

A simple and concise construction of a series of new quinoline-based isoindolin-l-ones, namely N-substituted-2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones, wherein the benzene moiety of isoindolin-l-one is replaced by a quinoline ring has been achieved via a two-step procedure, involving the one-step synthesis of ethyl 2-chloromethyl-quinoline-3-carboxylate followed by its one-pot reaction with various amines in a refluxing EtOH–AcOH (v/v, 10:1) solvent system. These newly synthesized compounds could be good candidates for the development of lead compounds for use in medicinal chemistry.     

Solvent-free synthesis of dibenzo[b,j][1,10]phenanthroline derivatives using Eaton’s reagent as catalyst

A new class of dibenzo[b,j][1,10]phenanthrolines has been prepared. The synthon acridones were achieved in very good yield by a one-pot reaction of 2-amino-5-chloro or 2′-chloro/flouro-substituted benzophenones with 1,2-cyclohexanedione in the presence of freshly prepared Eaton’s reagent (phosphorus pentoxide–methanesulfonic acid) without solvent, through Friedländer synthesis. Then these intermediates were reacted with 2-amino-3,5-dibromobenzaldehyde to afford 1,3-dibromo-10-chloro-8-aryl-6,7-dihydrodibenzo[b,j][1,10]phenanthroline. Also an one-pot reaction between 2?mol of 2-amino-5-chloro aryl benzophenones with 1?mol of 1,2-cyclohexanedione to get 3,10-dichloro-5,8-diaryl-6,7-dihydrodibenzo[b,j][1,10]phenanthroline has also been reported. The newly synthesized structures of the compounds were deduced by spectroscopic techniques.     

Synthesis of Nonionic Aroxylsulfonyl Carbamates

Novel aroxylsulfonyl carbamates containing polar head or core type were synthesized from the action of aroxysulfonylisocyanate on oligooxyethylmonomethylated ethers or glycols without solvent. At room temperature the reaction occurs rapidly with satisfactory yields. The synthetic pathway of isocyanate derivatives is achieved in a one-pot reaction in order to use low price commercially available compounds such as phenolic derivatives and chlorosulfonylisocyanate as starting materials. This new class of nonionic compounds contains one aromatic part and one polar part. All these compounds are monodisperse, that is, they include a perfectly defined number of oxyethylene units. The synthesis and characterization of these new series of carbamates are described.     

Regioselective hydrosilations. IV. The synthesis and polymerization of monomers containing epoxy and alkoxysilane groups

Using rhodium and platinum catalyzed regioselective hydrosilation, a series of α-hydrogen-ω-epoxy silane and siloxane compounds have been prepared in good yields. These intermediates have been further condensed with vinyltrimethoxysilane in subsequent hydrosilation reactions to prepare an interesting new class of ambifunctional monomers containing both epoxy and trimethoxysilane groups. It was further shown that these same compounds could be synthesized by a simplified “one-pot” two-step procedure. An investigation of the simultaneous cationic ring-opening polymerization of the epoxy groups and the acid-catalyzed condensation of the trimethoxysilyl groups was carried out. © 1993 John Wiley & Sons, Inc.     

Microwave assisted synthesis of ring junction heterocyclic antioxidants

A series of 6,7-dihydro-[1,2,4]triazolo[5,1-b]quinazolin-8(5H)-ones, 4a–o were synthesized via a one-pot, multicomponent reaction in the presence of water as a solvent under microwave irradiation using ceric ammonium nitrate as an oxidizing agent. This techno-chemical method provides a rapid construction of higher molecules in short duration with high yield. The adopted method was carried out in the presence of water without catalyst and yielded the compounds without any side products, and thus further purification of compounds by column chromatography was not required. All the synthesized compounds, 4a–o were screened for their 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. All the compounds, 4a–o possessed moderate antioxidant activity when compared to their standard antioxidant (ascorbic acid).     

Solution-phase parallel synthesis of novel 1,2,3,4-tetrahydroisoquinoline-1-ones as anticonvulsant agents

Following our previous studies in the field of anticonvulsant agents, we planned a one-pot solution-phase parallel synthesis (SPPS) of a small library of new 1,2,3,4-tetrahydroisoquinoline derivatives. The activity against audiogenic seizures in DBA/2 mice of the newly synthesized compounds has also been evaluated.     

一锅法合成4-(5-芳基-1,3,4-噻二唑-2-氨甲基)苯酚衍生物

以2-氨基-5-芳基噻二唑衍生物和对羟基苯甲醛为原料,经亲核加成/脱水、还原两步一锅法合成了一系列新的4-(5-芳基-1,3,4-噻二唑-2-氨甲基)苯酚衍生物,反应具有时间短、后处理简单等优点.采用元素分析,NMR,IR以及质谱等多种谱学技术对产物进行了详细表征.     

新农药研究（Ⅲ）：咪唑啉酮类化合物的合成

Rovral[3-(3,5-二氯苯基)-1-异丙氨基甲酰乙内酰脲]是一种优良的广谱杀菌剂和种子处理剂,由于3,5-二氯苯胺不易制备,本文采用其它取代苯胺作为起始原料,采用固态光气制备异氰酸酯,中间体未经分离,经缩合、关环“一锅法”反应,得到化合物Ⅰ,进一步反应得到Ⅱ、Ⅲ系列新化合物。     

取代-1H-吡唑-5-甲酸与取代噻二唑-2-氨的酰胺化合物的合成及生长素活性

采用"一锅法"合成3-(4-甲氧基苯基)-1H-5-吡唑甲酸乙酯,分别将吡唑环上1-位甲基化、4-位氯代后水解,得到2种吡唑羧酸;以取代羧酸和氨基硫脲为原料,三氯氧磷为脱水剂,合成6种5-取代-2-氨基-1,3,4-噻二唑化合物;再将吡唑结构单元及1,3,4-噻二唑结构单元以酰胺键结合在一起,合成了12种新的酰胺化合物,目标产物最终收率可达50%以上。用元素分析、IR和1HNMR测试技术确定了其结构。用小麦芽鞘法测试其生长素活性均不高,有的对小麦芽鞘生长显示抑制作用。