Synthesis,Structural Reassignment,and Antibacterial Evaluation of 2,18‐Seco‐Lankacidinol B

Lankacidins are a group of polyketide natural products with activity against several strains of Gram‐positive bacteria. We developed a route to stereochemically diverse variants of 2,18‐seco‐lankacidinol B and found that the stereochemical assignment at C4 requires revision. This has interesting implications for the biosynthesis of natural products of the lankacidin class, all of which possessed uniform stereochemistry prior to this finding. We have evaluated 2,18‐seco‐lankacidinol B and three stereochemical derivatives against a panel of pathogenic Gram‐positive and Gram‐negative bacteria.     

Highly Efficient One‐Pot Three‐Component Synthesis and Antimicrobial Activity of 2‐Amino‐4H‐chromene Derivatives

A remarkably efficient three‐component reaction to synthesize 2‐amino‐4H‐chromenes derivatives from malononitrile, various aromatic aldehydes, and orcinol was described at room temperature in CH₂Cl₂ in the presence of catalytic amount of triethylamine. In a facile one‐pot procedure, excellent yields of products were achieved in less than 1 h. Some of the synthesized 2‐amino‐4H‐chromenes derivatives demonstrated potent antibacterial activities against Gram‐positive bacteria including Staphylococcus aureus and Bacillus anthracis, indicated by disk method, minimum inhibitory concentration, and minimum bactericidal concentration approaches. However, none of the tested compounds expressed any antibacterial activities against Enterococcus faecalis and Gram‐negative bacteria.     

Convenient Synthesis and Biological Activity of Mono and Diacyl 2,5‐Dimercapto‐1,3,4‐thiadiazole Derivatives

New derivatives of 2,5‐dimercapto‐1,3,4‐thiadiazole substituted both at one or two exocyclic sulfur atoms with a series of aroyl or ethoxycarbonyl groups were synthesized in reactions of 2,5‐dimercapto‐1,3,4‐thiadiazole salts with appropriate acid chlorides or ethyl chloroformate in mild conditions. The products were characterized by spectroscopy (¹H NMR, ¹³C NMR, IR, and HRMS). Some from the synthesized compounds were screened in vitro and in vivo for antibacterial and antifungal activities against a panel of reference strains of microorganisms. The study revealed that ethyl S‐(5‐mercapto‐1,3,4‐thiadiazol‐2‐yl) carbonothioate seems to be the most active and versatile compound against Gram‐positive bacteria, Gram‐negative bacteria, and plant pathogenic fungi.     

Synthesis and Antimicrobial Activity of Some New N‐substituted‐5‐arylidene‐thiazolidine‐2,4‐diones

A total of 17 new N‐substituted derivatives ( 2b , 2c , 2d , 2e , 2f , 2g , 2h , 2i , 2j , 2k and 3b , 3c , 3d , 3e , 3f , 3g , 3h ) of 5‐((2‐phenylthiazol‐4‐yl)methylene) thiazolidine‐2,4‐dione ( 2a ) and 5‐(2,6‐dichloro‐ benzylidene)thiazolidine‐2,4‐dione ( 3a ) were synthesized. The structural elucidation of the newly synthesized compounds was based on elemental analysis and spectroscopic data (MS, ¹H NMR, ¹³C NMR), and their antimicrobial activities were assessed in vitro against several strains of Gram‐positive and Gram‐negative bacteria and one fungal strain (Candida albicans) as growth inhibition diameter. Some of them showed modest to good antibacterial activity against Gram‐negative Escherichia coli and Salmonella typhimurium and Gram‐positive Staphylococcus aureus, Bacillus cereus, and Enterococcus fecalis bacterial strains, whereas almost all the compounds were inactive against Listeria monocytogenes. All of the synthesized compounds showed moderate to very good activity against C. albicans.     

Hybrid 4‐Aminoquinoline‐1,3,5‐triazine Derivatives: Design,Synthesis, Characterization,and Antibacterial Evaluation

A series of novel 4‐aminoquinoline 1,3,5‐triazine derivatives were synthesized and characterized by FTIR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. The antibacterial activities of synthesized compounds were tested against three Gram‐positive bacteria, namely Bacillus subtilis (NCIM‐2063), Bacillus cereus (NCIM‐2156), and Staphylococcus aureus (NCIM‐2079), and four Gram‐negative bacteria, namely Proteus vulgaris (NCIM‐2027), Proteus mirabilis (NCIM‐2241), Escherichia coli (NCIM‐2065), and Pseudomonas aeruginosa (NCIM‐2036), using ciprofloxacin as reference standard drug. Results showed compound 9a and 9e as potent antibacterial agents against all bacterial strains except Bacillus cereus (NCIM‐2156). Copyright © 2014 HeteroCorporation     

Disperse Dyes Based on 5‐Arylazo‐thiazol‐2‐ylcarbamoyl‐thiophenes: Synthesis,Antimicrobial Activity and Their Application on Polyester

A series of novel 5‐arylazo‐thiazol‐2‐ylcarbamoyl‐thiophene derivatives was synthesized, and their chemical structures were secured by elemental and spectroscopic analyses. Their versatility for pharmaceutical purposes and textile dyeing as disperse dyes were reported. The synthesized dyes were applied to polyester fabrics by using high temperature dyeing method at 130°C. The dyed polyester fabrics displayed very good washing and perspiration fastness and moderate light fastness. Finally, the synthesized compounds showed biological activities against Bacillus subtilis, Staphylococcus aureus (Gram positive bacteria), Escherichia coli, and Pseudomonas aeruginosa (Gram‐negative bacteria), while no effect had been reported against fungi. The minimum inhibitory concentration of the most active compound was evaluated.     

Synthesis of Some 3‐(4‐Aryl‐benzofuro[3,2‐b]pyridin‐2‐yl)coumarins and Their Antimicrobial Screening

The synthesis of some 3‐(4‐aryl‐benzofuro[3,2‐b]pyridin‐2‐yl)coumarins 3a–r has been carried out by the reaction of 3‐coumarinoyl methyl pyridinium salts 1a–c with 2‐arylidene aurones 2a–f in the presence of ammonium acetate and acetic acid under Kröhnke's reaction conditions. All the synthesized compounds were characterized by analytical and spectral data. They have been screened for their antibacterial activity against Escherichia coli (ATCC 25922) as Gram‐negative bacteria, Bacillus subtillis (ATCC 1633) as Gram‐positive bacteria and antifungal activity against Aspergillus niger (ATCC 9029).     

An Efficient One‐Pot Synthesis of Highly Substituted Pyridone Derivatives and Their Antimicrobial and Antifungal Activity

A series of carboxamide and cyano functionalized pyridone derivatives 4a – q have been synthesized via one‐pot synthesis of various aldehydes 1a – q , acetoacetanilide 2 , and cyanoacetamide 3 . The reaction was simple and afforded pyridone derivatives in good yield, 89 to 93%. The novel pyridone derivatives were achieved by Hantzch one‐pot synthesis. Moreover, the synthesized compounds were screened against Gram‐positive and Gram‐negative bacteria and fungi for their activity. Among them, compound 4c shows highest inhibition at 4.25 mm against Staphylococcus aureus and 3.75 mm against Escherichia coli Gram‐positive and Gram‐negative bacteria, respectively.     

Synthesis,Antibacterial Activity,and Docking Studies of 1,2,3‐triazole‐tagged Thieno[2,3‐d]pyrimidinone Derivatives

Novel (1‐(substituted phenyl)‐1H ‐1,2,3‐triazol‐4‐yl)methyl‐2‐(4‐oxo‐5,6,7,8‐tetrahydrobenzo[1,2]thieno[2,3‐d ]pyrimidin‐3(4H )‐yl)acetate derivatives were synthesized. All the compounds showed significant antibacterial activity against Gram‐negative (Escherichia coli and Klebsiella pneumonia ) and Gram‐positive (Bacillus subtilis and Bacillus cereus ) bacteria. Particularly, (1‐(3‐nitrophenyl)‐1H ‐1,2,3‐triazol‐4‐yl)methyl‐2‐(4‐oxo‐5,6,7,8‐tetrahydrobenzo[1, 2]thieno[2,3‐d ]pyrimidin‐3(4H )‐yl)acetate was found to be most potent against E. coli , K. pneumonia , and B. subtilis with MIC 25 μg/ml. Molecular docking was also performed on purine riboswitch of B. subtilis and thiamine pyrophosphate riboswitch of E. coli .      

Synthesis and Antimicrobial Activity of Novel Azolopyrimidines and Pyrido‐Triazolo‐Pyrimidinones Incorporating Pyrazole Moiety

A new series of azolopyrimidine derivatives incorporating pyrazole moiety were synthesized by reaction of 1‐(pyrazol‐3‐yl)‐2‐propenone with a number of heterocyclic amines in the presence of a catalytic amount of acetic acid. The mechanism of formation of the products was also discussed, and the structure assigned was elucidated based on both elemental and spectral analyses data. In addition, 7‐(pyrazolyl)‐2‐thioxo‐5‐phenyl‐1,3‐dihydropyrido[2,3‐d ]pyrimidin‐4‐one was used as starting material for preparation of a new series of pyridotriazolopyrimidines via its reaction with a variety of hydrazonoyl chlorides in dioxane using triethylamines as catalyst. The assigned structure for these products was also proved via elemental analysis and spectroscopic techniques (IR, ¹H NMR, and Mass). Moreover, the antimicrobial activity of some selected examples of the new products was evaluated, and the results obtained revealed high activity of compound 20a against the Gram positive bacteria Staphylococcus aureus and the Gram negative bacteria Klebsiella pneumonie . All the tested compounds have no antifungal activity.     

Synthesis and antimicrobial evaluation of some new bicyclopyrazolone‐based thiopyran ring systems

A series of bicyclopyrazolones were synthesized from the condensation reaction of methyl 4‐oxotetrahydro‐2H‐thiopyran‐3‐carboxylate with hydrazine derivatives in ethanol. All synthesized products were characterized by FT‐IR, ¹H, and ¹³C NMR spectral data, elemental analyses, and mass spectrometry. The antibacterial and antifungal activities of these compounds were evaluated against Staphylococcus aureus and Bacillus subtilis as Gram‐positive bacteria, Escherichia coli and Pseudomonas aeruginosa as Gram‐negative bacteria, and the fungus Candida albicans. The results revealed that bicyclopyrazolones including an aryl or aryl sulfonyl group in the N‐2 position of the pyrazolone moiety are the most effective against all the microorganisms studied in this work.     

Novel 7‐Nitro‐1‐(Piperidin‐4‐yl)‐4,5‐Dihydro‐[1,2,4] Triazolo[4,3‐a]Quinoline‐Sulphonamide Derivatives as Antimicrobial Agents: Design,Synthesis, and Bio‐Activity

In attempt to search for more potent antimicrobial agents, a series of 7‐nitro‐1‐(piperidin‐4‐yl)‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinoline‐derived sulphonamides were synthesized. Their structures were established by elemental analyses, IR, and NMR (¹H and ¹³C) spectral data. The antibacterial activity of the obtained compounds was investigated against different Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Bacillus subtilis and Staphylococcus aureus) bacteria and antifungal activity against two fungal strains (Aspergillus niger and Aspergillus clavatus) using disk diffusion method at various concentrations (20, 40, 60, and 80 μg/mL). The study reveals that most of the title compounds showed significant antibacterial and fungal activity when compared with their respective standards streptomycin and griseofulvin.     

Synthesis and biological evaluation of new 4‐(4‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)phenyl)‐2‐phenylthiazole derivatives

A novel series of 4‐(4‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)phenyl)‐2‐substitutedthiazole derivatives ( 8a‐l) have been synthesized by [3 + 2] cycloaddition reaction of 4‐(4‐ethynylphenyl)‐2‐substitutedthiazole with substituted benzyl azide in aqueous DMF. Starting compounds 4‐(4‐ethynylphenyl)‐2‐substitutedthiazole ( 6a‐d ) were synthesized by reaction of 4‐(2‐substitutedthiazol‐4‐yl)benzaldehyde with Ohira‐Bestmann reagent in methanol. The structures of these novel triazole‐thiazole clubbed derivatives were confirmed by the spectral analysis. The title compounds ( 8a‐l ) were tested for antimycobacterial activity against Mycobacterium tuberculosis H37Ra active and dormant (MTB, ATCC 25177) and antimicrobial activity against standard Gram‐positive bacteria, Staphylococcus aureus (NCIM 2602) and Bacillus subtilis (NCIM 2162), and Gram‐negative bacteria, Escherichia coli (NCIM 2576) and Pseudomonas flurescence (NCIM 2059). Compounds 8a , 8b , 8c , and 8h reported good activity against B subtilis, compounds 8a , 8b , and 8c showed good activity against S aureus, and compound 8b showed good activity against dormant M tuberculosis H37Rv strain. Compounds 8b and 8c found more potent against Gram positive and dormant M tuberculosis H37Rv strains. These novel triazole‐thiazole clubbed analogues found to be a capable leads for further optimization and development.     

Synthesis and Antibacterial Activity of Novel (4‐Fluorophenyl)(4‐(naphthalen‐2‐yl)‐6‐aryl‐2‐thioxo‐2,3‐dihydropyrimidin‐1(6H)‐yl)methanone Derivatives

A novel series of (4‐fluorophenyl)(4‐(naphthalen‐2‐yl)‐6‐aryl‐2‐thioxo‐2,3‐dihydropyrimidin‐1(6H)‐yl)methanone derivatives were synthesized from reaction of 6‐(naphthalen‐2‐yl)‐4‐aryl‐3,4‐dihydropyrimidine‐2(1H)‐thiones with 4‐fluorobenzoylchloride in dichloromethane in the presence of triethylamine. The synthesized compounds were screened for antibacterial activity against Gram positive bacteria, namely, Staphylococcus aureus ATCC25923 and Listeria monocytogenes MTCC657, and Gram negative bacteria, namely, Escherichia coli ATCC25922 and Klebsiella pneumoniae ATCC700603, respectively. Some of the tested compounds showed significant antimicrobial activity.     

Synthesis,Antimicrobial Activity and Molecular Modeling of Some Novel 5‐Aminopyrazole,Pyrazolo[1,5‐a]pyrimidine,Bispyrazole and Bispyridone Derivatives Containing Antipyrinyl Moiety

2‐Cyano‐N‐(antipyrin‐4‐yl)‐3‐(ethylthio)‐3‐(naphthalen‐1‐ylamino)acryl‐amide 4 was achieved via a one‐pot, three‐component reactions of cyanoacetamide derivative 2 , 2‐naphthyl isothiocyanate, and diethyl‐sulphate. The cyano acrylamide derivative 4 was hydrazinolysis to furnish 5‐aminopyrazole 5 ; many pyrazolo[1,5‐a ]pyrimidines 10a,b, 14, 15, 16, 18, and 20 have been synthesized via treatment of 5 with some electrophilic reagents. Also, ternary condensation of cyanoacetamide derivative 2 , terephthalaldehyde, and active methylene derivatives afforded bispyridone derivatives 21a,b . The structures of the new compounds were confirmed on the basis of elemental analysis and spectral data. Representative compounds of the synthesized products were tested and evaluated as antimicrobial. In general, the novel‐synthesized compounds showed a good antimicrobial activity against Gram‐positive bacteria, Gram‐negative bacteria, and antifungal activity against Azithromycin and Ketoconazole . The molecular modeling of the 21a and 21b as representative examples of the synthesized compounds has been drawn, and their molecular parameters were calculated.     

Synthesis and Antimicrobial Evaluation of Some New 4,5′‐Bisthiazoles

Thiazole and bisthiazole derivatives represent a prevalent scaffold in the antimicrobial drug discovery. Therefore, we have decided to synthesize some new series of 4,5′‐bisthiazoles. A total of 17 compounds were synthesized, their structural elucidation being based on elemental analysis (C,H,N,S) and spectroscopic data (MS and ¹H NMR). Their in vitro antimicrobial activities were assessed against several Gram‐positive and Gram‐negative bacteria strains and also against one fungal strain (Candida albicans) using the difusimetric method. Some of the compounds showed modest to good antibacterial activity against Gram‐negative Escherichia coli and Salmonella typhimurium and Gram‐positive Staphylococcus aureus and Bacillus cereus bacterial strains. All of the synthesized compounds showed moderate to very good antifungal activity against C. albicans.     

Substrate‐Controlled Asymmetric Total Syntheses of Microcladallenes A,B, and C Based on the Proposed Structures

Substrate‐controlled asymmetric total syntheses of (+)‐microcladallenes A, B, and C have been accomplished based on the proposed structures. The syntheses of microcladallenes A and B confirmed the structures and absolute configurations of both natural products. However, the synthesis of microcladallene C, which includes seven stereogenic centers and an (R)‐bromoallene in its compact C₁₅ framework, brought the realization that its proposed structure must be revised. The introduction of C12‐bromine into these natural products with retention of configuration relied on TiBr₄‐mediated nucleophile‐assisting leaving group brominations, the stereochemical outcome of which could be attributed, at least in part, to an oxonium or halonium ion formation–fragmentation sequence through intricate neighboring group participation. In addition, the pivotal β‐oriented vicinal cis‐dichloride function in microcladallene C was elaborated through a novel tandem Cl₂‐induced electrophilic cyclization/imidate chlorination process. The positive rotations of these natural products with an (R)‐bromoallene constitute exceptions to Lowe’s rule for reasons yet to be determined.     

Microwave‐assisted Synthesis,Characterization, and Density Functional Theory Study of Biologically Active Ferrocenyl Bis‐pyrazoline and Bis‐pyrimidine as Organometallic Macromolecules

Organometallic macromolecules such as ferrocenyl bis‐pyrazoline ( 2 , 3 ) and bis‐pyrimidine ( 4 , 5 ) derivatives were synthesized by reacting ferrocenyl bis‐chalcone 1 with thiosemicarbazide/phenylhydrazine/guanidine hydrochloride/thiourea, respectively, under microwave irradiation. Ferrocenyl bis‐chalcone 1 was synthesized by reacting acetyl ferrocene with terephthalaldehyde. Synthesized compounds were characterized by using IR, ¹H NMR, ¹³C NMR, EI‐MS, and elemental analysis. In vitro antibacterial activity against two Gram‐negative and two Gram‐positive bacteria was determined by the disc diffusion assay. Moreover, minimum inhibition concentrations were also measured with reference to chloramphenicol. Thioamide functionally containing ferrocenyl bis‐pyrazoline derivative 2 shows the best antibacterial activity on Escherichia coli and Salmonella typhimurium, among all tested compounds including the reference drug chloramphenicol. The structure–activity relationship is also developed by using computational calculations with density functional theory (DFT)/B3LYP method.     

Synthesis,Antimicrobial, and Antioxidant Screening of Aryl Acetic Acid Incorporated 1,2,4‐Triazolo‐1,3,4‐Thiadiazole Derivatives

Some novel [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole derivatives were synthesized from aryl acetic acids. All the synthesized derivatives were selected for the screening of antibacterial potential against Gram‐positive bacteria [Staphylococcus aureus (MTCC 3160) and Micrococcus luteus (MTCC 1538)] and Gram‐negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)] and antifungal potential against Aspergillus niger (MTCC 8652) and Candida albicans (MTCC 227), and free radical scavenging activity through 2,2‐diphenyl‐2‐picrylhydrazyl hydrate method. The compounds TH‐4 , TH‐13 , and TH‐19 were found to be more potent antimicrobial agents compared to standard drugs. The compounds TH‐3 , TH‐9 , and TH‐18 also showed significant antimicrobial activity. The compound TH‐13 showed antioxidant activity with IC₅₀ value better than the standard compound. The structures of all the synthesized compounds were confirmed by Fourier transform infrared, ¹H‐NMR, liquid chromatography–mass spectrometry, and CHN analyzer.     

Long‐Chain Alkyl Cyanides: Unprecedented Volatile Compounds Released by Pseudomonas and Micromonospora Bacteria

The analysis of volatiles from bacterial cultures revealed long‐chain aliphatic nitriles, a new class of natural products. Such nitriles are produced by both Gram‐positive Micromonospora echinospora and Gram‐negative Pseudomonas veronii bacteria, although the structures differ. A variable sequence of chain elongation and dehydration in the fatty acid biosynthesis leads to either unbranched saturated or unsaturated nitriles with an ω−7 double bond, such as (Z )‐11‐octadecenenitrile, or methyl‐branched unsaturated nitriles with the double bond located at C‐3, such as (Z )‐13‐methyltetradec‐3‐enenitrile. The nitrile biosynthesis starts from fatty acids, which are converted into their amides and finally dehydrated. The structures and biosyntheses of the 19 naturally occurring compounds were elucidated by mass spectrometry, synthesis, and feeding experiments with deuterium‐labeled precursors. Some of the nitriles showed antimicrobial activity, for example, against multiresistant Staphylococcus aureus strains.