Band 25, Heft 1

Novel magnesium(II) porphyrazine with peripheral methyl(3,5-dibromophenylmethyl)amine groups was synthesized in a multi-step procedure starting from commercially available diaminomaleonitrile. All intermediates and the final macrocycle were characterized using UV–Vis, FT-IR, MS and various NMR techniques. The absorption and emission properties of the macrocycle were evaluated in N,N -dimethylformamide, dimethyl sulfoxide, and dichloromethane. The potential photosensitizing activity was evaluated by assessing the ability of the macrocycle to generate singlet oxygen in dimethyl sulfoxide and N,N -dimethylformamide.

A series of novel imidazo[4,5- b ]pyridine derivatives were synthesized and their structures were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The results of bioassays showed that some compounds exhibit good fungicidal activity against Puccinia polysora In particular, compound 7b showed an EC 50 value of 4.00 mg/L, which was comparable with that of tebuconazole. Besides, preliminary structure-activity relationship was discussed.

A simple method for the synthesis of the title compounds by an efficient in-situ reduction and cyclization reactions of aromatic aldehydes, tert -butyl 2,4-dioxopiperidine-1-carboxylate and 5-nitro-1 H -indazole or 6-nitro-1 H -indazole was developed.

7-Allylindolines are valuable synthons for designing biologically active molecular libraries. Lewis acid catalyzed amino-Claisen rearrangement provides a one pot synthetic entry to these heteroarenes. In this context, Zinc chloride (ZnCl 2 )–N,N-dimethylformamide system efficiently catalyzed amino-Claisen rearrangements of 1- N -allylindolines to 7-allylindolines. The rearrangement is influenced by stereoelectronic effects of substituents present in 1- N -allylindolines. The substrates containing electron donating functionalities underwent rearrangement at lower temperature than substrates with electron withdrawing functional groups. The regioselectivity of the process is governed by the substitution pattern on allyl moiety in 1- N -allylindoline as well as ZnCl 2 catalyst loading in the reaction system.

( E )- N ’-Benzylidene-7-methyl-2-propyl-1 H -benzo [ d ]imidazole-5-carbohydrazides (5a-r) have been synthesized from 7-methyl-2-propyl-1 H -benzo[ d ]imidazole-5-carbohydrazide ( 3 ) by condensing with different aromatic aldehydes ( 4a-r ). Title compounds ( 5a-r ) were evaluated for in vitro antioxidant activity and based on their potential for antioxidant property, selected compounds 5d and 5m-p were screened for in vivo anti-inflammatory and analgesic activity. The results indicate that the compound 5o and 5p are effective against anti-inflammatory and analgesic activity. The biological data was further supported by molecular docking studies, which revealed the binding pattern and the affinity of the molecules in the active site of COX-2.

New pyrazolothienopyrimidines were synthesized. The key intermediate 4-aminothieno[2,3- c ]pyrazole-5-carbonitrile 1 was converted to the chloroacetyl amino derivative 2 followed by nucleophilic substitution and Dimorth rearrangement upon treatment with nitrogen nucleophiles to give the pyrimidinones 3a-c . Treatment of 3a with formaldehyde and with triethyl orthoformate afforded the respective tetracyclic derivatives 4 and 5 . Condensation of the amino group in the o -aminocarbonitrile 1 with triethyl orthoformate followed by cycloaddition reaction with hydrazine led to the formation of pyrazolothienopyrimidine 8 . Compound 8 was used as a synthetic precursor to heterocyclic compounds comprised of pyrazole, triazole, triazine, and triazepine derivatives.

A series of novel chiral 5-(substituted aryl)-1,3,4-thiadiazole derivatives was synthesized in an enantioselective three-component Mannich reaction using cinchona alkaloid squaramide catalyst with excellent enantioselectivities (up to >99% enantiomeric excess (ee)). The bioassay results showed that these derivatives possessed good to excellent activities against tobacco mosaic virus (TMV).

Nitro-substituted heteroaromatic carboxamides 1a-e were synthesized and tested against three Mycobacterium tuberculosis cell lines. The activities can be explained in terms of the distribution of the electronic density across the nitro-substituted heteroaromatic ring attached to the amide group. 1,3,5-Oxadiazole derivatives 1c-e are candidates for the development of novel antitubercular agents. Ongoing studies are focused on exploring the mechanism by which these compounds inhibit M. tuberculosis cell growth.

The regiospecific 1,3-dipolar cycloaddition of 1,5-dihydropyrrol-2-one and arylnitrile oxides derivatives have been investigated. The asymmetric induction expected by the chiral centre of the 5-hydroxy-3-methyl-1,5-dihydropyrrol-2-one derivatives was very effective, single diastereoisomers anti -3 was formed. The diastereoselectivity was linked to the destabilization of the syn transition state as a result of the electrostatic repulsion between the hydroxy group of the dihydropyrrol-2-one derivatives and the atom oxygen of the dipole.

Two pyrazol-4-carboxamides, 3-(difluoromethyl)-N-(mesitylcarbamoyl)-1-methyl-1 H -pyrazole-4-carboxa-mide ( 7a ) and 3-(difluoromethyl)-N-((3,5-dimethylphenyl) carbamoyl)-1-methyl-1 H -pyrazole-4-carboxamide ( 7b ) were synthesized and their structures were confirmed by the aid of 1 H NMR and HRMS analyses. The structure of the pyrazole-4-carboxamide, 7a was also determined by X-ray diffraction. The preliminary activity results demonstrate that these two compounds exhibit good inhibitory activity against Botrytis cinerea . Further docking results indicated that the key active group is difluoromethyl pyrazole moiety.

In this paper, we present a Lewis-acid-promoted reaction of 2-benzoylbenzaldehyde and trialkenyl phosphites, which resulted in the formation of polycyclic phosphonates. The reaction proceeded via nucleophilic attack of trialkenyl phosphite on the carbonyl carbon of 2-benzoylbenzaldehyde. The subsequent intramolecular Diels-Alder reaction led to the formation of the cyclic phosphonate.

An efficient, short and, a convenient asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol ( 2 ) and zeaenol ( 1 ) have been achieved in 7 and 9 linear steps with the high overall yield of 32% and 21% respectively, from the known intermediate 13 . Mitsunobu inversion, De Brabander’s protocol for macrolactonisation, Heck cross-coupling, diastereoselective alkyne aldehyde coupling and Ohira–Bestmann alkynylation are the key reactions.

A method is developed for in situ generation of 1,3-dioxan-5-one derivatives 2 . These compounds are simple precursors for accessing carbohydrate structures and previously had to be produced via stepwise procedures using excessive amounts of reagents. In the present work, three different derivatives of 2 were synthesized via the reaction of trialkoxyalkanes with dihydroxyacetone dimer 1 in the presence of acetic acid as the catalyst. In the same pot, derivatives of 2 were reacted with aromatic aldehydes and 30 mol% of pyrrolidine to obtain high yields of the respective bischalcones 3 within short time periods.

A series of novel perfluoropropan-2-yl-based quinoline derivatives was designed and synthesized utilizing tebufloquin as the lead compound. The structures of all the newly synthesized compounds were confirmed by spectroscopic data 1 HNMR, MS and elemental analysis. The results of bioassay indicated that these compounds exhibited potent fungicidal activities against Erysiphe graminis . Especially, compound 8c displayed excellent activity with EC 50 value at 1.48 mg / L, which was better than that of the commercialized fungicide --- tebufloquin. The structure-activity relationship for these new compounds was also discussed.

Copper-catalyzed Alkyne-Azide Cycloaddition (CuAAC) click chemistry robustness has been demonstrated over recent years to produce 1,2,3-triazoles with excellent yields at mild conditions with simple purification methods. However, the consequences of having copper paramagnetic traces in final products, which complicate spectroscopic assignments and can produce inaccurate conclusions, has been scarcely discussed. Herein we present a strategy that combines X-Ray Diffraction (XRD) with 13 C- paramagnetic Nuclear Magnetic Resonance spectroscopy, in order to demonstrate the presence of paramagnetic metal traces at standard Huisgen synthesis and purification conditions. We also demonstrate that the derivatization of 1,4-disubstituted-1,2,3-triazoles to produce 1,3,4,-trisubstituted-1,2,3.triazolium salts, promotes an efficient removal of Cu(II/I) moieties. Evidence of paramagnetic metal moieties is given using XRD structural analysis of abnormalities in torsional angles between substituents and the 1,2,3-triazole center, in parallel to 13 C- paramagnetic NMR chemical shift and line width analysis. As model systems to demonstrate the importance of characterizing paramagnetic traces, we present the synthesis of novel 1-((3s,5s,7s)-adamantan-1-yl)-4-cyclopropyl-1H-1,2,3-triazole and its derivatized 1-((3s,5s,7s)-adamantan-1-yl)-4-cyclopropyl-3-methyl-1H-[1,2,3]-triazol-3-ium triflate salt.

A pyrimidinethione derivative namely, 6-(1,3-diphenyl-1 H -pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile, was readily synthesized and reacted with carbon electrophiles in an attempt to synthesize selected fused heterocycles. The reactivity of 6-(1,3-diphenyl-1 H -pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile was investigated towards selected nitrogen nucleophiles. Thiation and hydrolysis reactions of the tetrahydropyrimidine derivative were investigated. Antitumor and antimicrobial activity evaluation of some of the synthesized products exhibited promising results.

Herein is described a diastereoselective Michael addition of Grignard reagents to α, β- unsaturated diethyl malonates incorporated with a 2-oxazolidone chiral auxiliary. The catalyst-free Michael addition proceeds with good chemical efficiency and excellent stereoselectivity; and it provides new thoughts to the asymmetric synthesis of β-substituted β 3 amino acid derivatives.

An efficient method has been developed for the synthesis of 1,2,3 triazole-linked benzimidazole through a copper-catalyzed click reaction in ethanol at 50°C. A broad range of aromatic azides were successfully reacted with n -propynylated benzimidazole via copper-catalyzed azide-alkyne cycloaddition reactions in the absence of a ligand. This method offers many advantages including short reaction times, low cost, and simple purification procedures.

Based on readily available N -(2,2,2-trichloro-1-hydroxyethyl)carboxamides, N -(2,2,2-trichloro-1-(3-(3-mercapto-4 H -1,2,4-triazol-4-yl)thioureido)ethyl) carboxamides, dehydrosulfurization–under the influence of excess HgO–led to the formation of N -(1-([1,2,4] triazolo[3,4- b ][1,3,4]thiadiazol-6-ylamino)-2,2,2-trichloroethyl)carboxamides. The reaction was carried out in boiling glacial acetic acid for 1-1.5 hours. The cyclization products were obtained in 42-62% yields and easily isolated from the reaction mixture. The structure of all synthesized compounds was confirmed by complex spectral studies.

This paper discloses an efficient one-pot protocol to convert easily accessible 3-nitropyridines to 3-acetamidopyridin-2-yl 4-methylbenzenesulfonate derivatives which are core structures of many pharmaceutical molecules. The strategy successfully combined a three-step reaction in one pot via progressively adding different reactants at rt. The reaction displays good functional group tolerance and regioselectivity. Structurally diversified 3-nitropyridine could be time-efficiently (3.5 h) derivatized to various functional 2- O ,3- N -pyridines which are apt for further elaborations. The transformation was amenable to gram-scale synthesis.

Novel congeners of naphthalene substituted benzo[c]coumarins ( 2a - f ) were synthesized by reaction of various 3-coumarinoyl methyl pyridinium bromide salts (1a-d) with a selected set of acetyl naphthalene in the presence of sodium acetate in refluxing glacial acetic acid. Structures of the synthesized compounds were confirmed by elemental analysis and by various spectroscopic techniques such as 1 H-NMR, 13 C-NMR, DEPT, and MS spectral data. Synthesised compounds were screened for antibacterial activity and cytotoxicity against different human cancer cell lines including cervix cancer (HeLa), breast cancer (MCF-7) and lung cancer (A549) using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Although with varying degrees, a significant growth inhibitory and cytotoxic effects were observed on all three cancer cell lines. Compounds 2b and 2e showed significant growth inhibitory and cytotoxicity against aforementioned cancer cell lines.

A green method has been developed for the synthesis of N -arylsulfonylhydrazones via a simple grindstone procedure. By grinding mixtures of benzensulfonyl hydrazides and a series of aryl aldehydes or ketones in the mortar using L-tyrosine as catalyst, 24 N -arylsulfonylhydrazones were synthesized in a few minutes with high yield. All compounds were screened for their antibacterial activities. Most of them exhibit some antibacterial activities especially for 3d, 3l and 3v showing high activity against Staphylococcus aureus and Escherichia coli .

Spiro[cyclohexane-1,3’-indoline]-2,2’-diones were easily prepared in good to high yields by the oxidation of N -aryl- N -methyl-2-oxocyclohexane-1-carboxamides in one pot with a short reaction time. The spiroindolinediones could be important for the total synthesis of natural products.

Six N -glycosyl benzofuran derivatives were synthesized by the catalysis of organic bases and condensation agents. The benzofuran derivatives were obtained by the reaction of various salicylaldehydes in acetone, and then hydrolyzed to the corresponding carboxylic acids. Finally, the target compounds were synthesized by acylation and the reaction conditions were optimized. The acetylcholinesterase (AChE) inhibitory activity of the desired compounds was tested using Ellman’s method. Most of the compounds showed acetylcholinesterase-inhibition activity; N -(2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2 H -pyran-3-yl)benzofuran-2-carbxamide ( 5a ) showed the best acetylcholinesterase inhibition, with an inhibitory rate of 84%.

A series of substituted 4 H -pyrans derivatives were synthesized by a one-pot, multi-component reaction of aromatic aldehydes, malononitrile, and pyrazolone derivatives or active methylene carbonyl compounds such as dimedone, in the presence of 1,3-dimethyl imidazolium dimethyl phosphate [DMImd-DMP] as a catalyst in aqueous ethanol. Recyclability of the catalyst, high yields, simple product isolation and high atom economy are the noteworthy aspects of this protocol.