ABSTRACT
A simple, first stereoselective total synthesis of botryolide-E has been described. The synthesis started from propylene oxide employing Jacobsen's hydrolytic kinetic resolution (HKR), selective epoxide opening, sharpless asymmetric dihydroxylation, one pot acetonide deprotection and lactonization as key steps. Further, the synthesis confirms the absolute configuration of the natural product botryolide-E and we evaluated the biological behavior of natural product botryolide-E against a panel of bacteria and fungi. Botryolide-E exhibits significant potent activity against Staphylococcus aureus (MTCC 96) (6.25 µg/ml), good against Escherichia coli (MTCC 443) (12.5 µg/ml), Bacillus subtilis (MTCC 441) (25 µg/ml) and compound 1 exhibited good to moderate antifungal activity.
Subject(s)
4-Butyrolactone/analogs & derivatives , Acetates/chemical synthesis , Anti-Bacterial Agents/chemical synthesis , Antifungal Agents/chemical synthesis , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/chemistry , 4-Butyrolactone/pharmacology , Acetates/chemistry , Acetates/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Bacillus subtilis/drug effects , Escherichia coli/drug effects , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , StereoisomerismABSTRACT
A simple and highly efficient synthetic route has been developed for synthesis of (R)-rugulactone (1a), (6R)-((4R)-hydroxy-6-phenyl-hex-2-enyl)-5,6-dihydro-pyran-2-one (1b) and its 4S epimer 1c by employing proline-catalyzed alpha-aminooxylation, Sharpless epoxidation, Mitsunobu reaction as chirality introuducing steps. The antibacterial and antifungal activity of the compounds 1a, 1b and 1c were evaluated. 1a and 1b showed better antibacterial activity against Pseudomonas aeroginosa (MIC=12.5 microg/ml for 1a, 25 microg/ml for 1b) Klebsiella pneumonia (MIC=25 microg/ml for 1a). Compounds (1a, 1b, 1c) exhibited good to moderate antifungal activity.
Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Lactones/chemistry , Lactones/pharmacology , Pyrones/chemistry , Pyrones/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemical synthesis , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/drug therapy , Cryptocarya/chemistry , Fungi/drug effects , Humans , Lactones/chemical synthesis , Microbial Sensitivity Tests , Mycoses/drug therapy , NF-kappa B/antagonists & inhibitors , Pyrones/chemical synthesis , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The formation of N- and O-propargylated quinazoline derivatives 2, 3 from quinazol-4-ones 1 was theoretically predicted by optimizations at B3LYP/6-31G* level, analysed kinetically and thermodynamically. Theoretical predictions are validated by experiment to observe the trends and found deviation. Thus, compound 1 was propargylated in basic media to obtain compound 2 and 3 in definite proportions. Each compound was further subjected to [3+2] cycloaddition using perfluoroalkyl azides through Click reaction under Sharpless conditions, and obtained a series of novel perfluoroalkyl-1H,1,2,3-triazol-4-yl substituted quinazolines 4, 5, and 6. All the compounds were screened for antimicrobial activity and identified potential compounds.
Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Quinazolines/chemistry , Quinazolines/pharmacology , Triazoles/chemistry , Anti-Infective Agents/chemical synthesis , Bacteria/drug effects , Fungi/drug effects , Microbial Sensitivity Tests , Models, Molecular , Molecular Conformation , Quinazolines/chemical synthesis , Reproducibility of Results , ThermodynamicsABSTRACT
2-Chloro-5-methylpyridine-3-olefin derivatives (3a-e) have been synthesized from 2-chloro-5-methylnicotinaldehyde (1) and studied their photochemical E (trans)-->Z (cis) isomerization upon direct irradiation and triplet sensitized excitation for the first time. The triplet sensitized excitations of the compounds yielded high Z (4a-e) isomer composition, whereas the direct excitation results in less Z (4a-e) isomer composition, indicating triplet pathway is very efficient in converting the E (trans)-->Z (cis) isomer. Thus synthesized E (3a-c and 3e) and generated Z (4a-c and 4e) isomers were tested for antimicrobial activity. Antifungal activity of these pyridine derivatives are closely comparable to the standard used.
Subject(s)
Alkenes/chemistry , Alkenes/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Pyridines/chemistry , Pyridines/pharmacology , Bacteria/drug effects , Fungi/drug effects , Isomerism , Photochemistry , Structure-Activity RelationshipABSTRACT
A versatile and efficient method has been developed for the synthesis of bis(indolyl)methanes by using aluminium triflate (0.5 mol%) as a novel catalyst. Further, some of the synthesized compounds were evaluated for their efficacy as antibacterial and antifungal activities. Most of the compounds have shown moderate to good inhibitory activity.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Indoles/chemical synthesis , Methane/chemistry , Anti-Bacterial Agents/pharmacology , Catalysis , Indoles/pharmacology , Methane/analogs & derivatives , Methane/pharmacology , Microbial Sensitivity TestsABSTRACT
A series of novel 7,8 and 1,8 imidazo fused quinolone carboxamides are synthesized and evaluated against antibacterial activity. 1,8 Imidazo fused quinolones exhibit moderate antibacterial activity. Molecular modeling studies were carried out to optimize the pharmacophore.
Subject(s)
Amides/chemistry , Amides/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Drug Design , Quinolones/chemistry , Amides/chemical synthesis , Anti-Bacterial Agents/chemical synthesis , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
Indazole regioisomers such as 3-amino-4-(trifluoromethyl)-6-phenyl-1H-indazole-7-carbonitrile 1 and 3-amino-6-(trifluoromethyl)-4-phenyl-1H-indazole-7-carbonitrile 2 were independently reacted with formaldehyde followed by unsymmetrical, symmetrical and cyclic electron rich olefins in presence of GdCl(3) as catalyst and obtained pyrimidine fused indazole derivatives 3 and 4, respectively. The reaction is found to be concerted and an exclusive product is formed. Representative examples of compounds 3 and 4 were screened against Gram-positive, Gram-negative bacteria and fungal species such as yeast and filamentous fungi in vitro. Compound 3f showed significant activity against all species of Gram-positive and Gram-negative bacteria, whereas compounds 3h and 4a showed the least activity with reference to penicillin as well as streptomycin. Similarly compound 3c showed promising activity against yeast and filamentous fungi whereas compound 3f is inactive at the maximum concentration of 150 microg/mL.
Subject(s)
Anti-Bacterial Agents/chemistry , Antifungal Agents/chemistry , Gadolinium/chemistry , Indazoles/chemistry , Pyrimidines/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Catalysis , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Pyrimidines/pharmacologyABSTRACT
In continuation of our earlier work on benzothiadiazines, we have prepared a series of nitrofuran, nitrothiophene and arylfuran coupled benzothiadiazines and evaluated them for antimycobacterial and antibacterial activities. One of the compounds 2f has shown good in vitro antimycobacterial activity. All the synthesized compounds have shown moderate to good antibacterial activity.
Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Benzothiadiazines/chemical synthesis , Benzothiadiazines/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Indicators and Reagents , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Structure-Activity RelationshipABSTRACT
Series of substituted-s-triazines (1-22) were synthesized and evaluated for their in vitro antibacterial activity against six representative Gram-positive and Gram-negative bacterial strains. Many compounds have displayed comparable antibacterial activity against Bacillus sphaericus and significantly active against other tested organisms with reference to streptomycin.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Triazines/chemical synthesis , Triazines/pharmacology , Anti-Bacterial Agents/chemistry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, Infrared , Triazines/chemistryABSTRACT
Baylis-Hillman acetates were synthesized from substituted 2-chloronicotinaldehydes and were conveniently transformed into multisubstituted quinolines and cyclopenta[g]quinolines on reaction with nitroethane or ethyl cyanoacetate via a successive S(N)2'-S(N)Ar elimination strategy. Thus, synthesized quinolines were evaluated for antimicrobial activity and found having substantial antibacterial and antifungal activity.
Subject(s)
Aldehydes/chemistry , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemistry , Quinolines/chemistry , Acetates/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Bacteria/drug effects , Fungi/drug effects , Quinolines/chemical synthesis , Quinolines/pharmacologyABSTRACT
The natural product, chrysin (5,7-dihydroxy flavone), obtained from Oroxylum indicum, exhibits numerous biological activities including anticancer, anti-inflammatory, and antiallergic activities. Three series of chrysin analogues were prepared, in which chrysin and heterocyclic moieties are separated by 3-carbon, 4-carbon, and 6-carbon spacers. All the derivatives were screened for antibacterial activity against a panel of susceptible and resistant Gram-positive and Gram-negative organisms. It was observed that most of the derivatives displayed significant activity as compared to their parent compound (chrysin).
Subject(s)
Anti-Infective Agents/pharmacology , Chemistry, Pharmaceutical/methods , Flavonoids/chemistry , Flavonoids/chemical synthesis , Plant Extracts/metabolism , Anti-Allergic Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Carbon/chemistry , Drug Design , Drug Evaluation, Preclinical , Flavonoids/metabolism , Microbial Sensitivity Tests , Models, Chemical , Morpholines/chemistry , Structure-Activity RelationshipABSTRACT
Five clerodane diterpenoids have been isolated from the aerial parts of Pulicaria wightiana along with 3'5,6-trihydroxy-3,4',7-trimethoxyflavone and 2-methyl-5-hydroxy-chroman-4-one. The structures and stereochemistry of the compounds were established from spectral (mainly 1D and 2D NMR) studies. The last two compounds were not reported earlier from this plant. The antibacterial activity of the diterpenoids were studied.