Nonsteroidal Anti‐inflammatory Drug‐based N‐Allylidene Benzohydrazides and 1‐Acyl‐2‐pyrazolines: Their Synthesis as Potential Cytotoxic Agents In Vitro

A series of 1‐acyl‐2‐pyrazoline derivatives derived from nonsteroidal anti‐inflammatory drugs was designed as potential anticancer agents. Synthesis of these compounds was carried out via the condensation reaction of chalcones and acid hydrazides under heating. The methodology did not require the use of any costly reagents or catalysts, and the acid hydrazide reactants were readily prepared from mefenamic acid or ibuprofen. A variety of 1‐acyl‐2‐pyrazolines was prepared in good to excellent yields. An N‐allylidene benzohydrazide intermediate was isolated during the reaction optimization study, the structure of which was confirmed unambiguously by X‐ray single crystal data. A range of N‐allylidene benzohydrazides were also prepared in good yields. Some of the compounds synthesized showed promising cytotoxic activities when tested against HCT‐15 human colon cancer cell line in vitro.     

Studies towards the total synthesis of (−)-borrelidin: a strategy for the construction of the C11-C15 cyanodiene fragment and the utility of RCM for macrocyclization using model systems

We report here a methodology for the construction of a conjugated cyanodiene synthon and the propensity of such synthons to participate in the olefin metathesis reaction. To this end, we have developed a strategy for the construction of the C11-C15 fragment of borrelidin and demonstrated the utility of the RCM reaction in the preparation of the final macrolide. To our knowledge, this is the first example of a RCM with a nitrile functionality on a diene.     

Asymmetric synthesis of (4S,5S)-2-oxo-4-phenyloxazolidine-5-carboxylic acid using a 1,2-addition of PhMgBr to an N-sulfinimine derived from (R)-glyceraldehyde acetonide and (S)-t-BSA

We report an asymmetric synthesis of (4S,5S)-2-oxo-4-phenyloxazolidine-5-carboxylic acid via stereoselective addition of phenylmagnesium bromide (PhMgBr) to an N-sulfinimine derived from (R)-glyceraldehyde acetonide. (S)- and (R)-Glyceraldehyde acetonides, important chiral synthons in synthetic organic chemistry, are prepared from the corresponding epichlorohydrin using an identical synthetic methodology.     

Quantitative estimation of riluzole in human plasma by LC-ESI-MS/MS and its application to a bioequivalence study

A novel simple, sensitive, selective, and rapid high-performance liquid chromatography coupled with tandem mass spectrometry method was developed and validated for quantification of riluzole in human plasma. The chromatography was performed by using a Zorbax-SB-C18 (4.6 × 75 mm, 3.5 μm) column , isocratic mobile phase 0.1% formic acid/acetonitrile (10:90 v/v), and an isotope-labeled internal standard (IS), [¹³C,¹⁵N₂]riluzole. The extraction of drug and internal standard was performed by liquid–liquid extraction and analyzed by MS in the multiple reaction monitoring (MRM) mode using the respective [M+H]⁺ ions, m/z 235.0/165.9 for riluzole and m/z 238.1/169.0 for the IS. The calibration curve was linear over the concentration range 0.5–500.0 ng/ml for riluzole in human plasma. The limit of quantification (LOQ) was demonstrated at 0.5 ng/ml. The within-batch and between-batch precision were 0.6–2.3% and 1.4–5.7%, and accuracy was 97.1–101.1% and 98.8–101.2% for riluzole respectively. Drug and IS were eluted within 3.0 min. The validated method was successfully applied in a bioequivalence study of riluzole in human plasma.     

A Validated LC Method for Separation and Quantification of Voriconazole and Its Enantiomer

A simple liquid chromatographic method was developed for the separation and quantification of voriconazole and its enantiomer in drug substance. The separation was achieved on Chiral cel-OD (250 mm × 4.6 mm × 10 μm) using mobile phase consisting of n-hexane and ethanol in the ratio 9:1 (v/v) with a flow rate of 1.0 mL min⁻¹, at 27 °C column temperature and detection at 254 nm with an injection volume of 20 μL. Ethanol was used as diluent. The method is capable of detecting the (2S, 3R) enantiomer down to 0.0075% and can quantify down to 0.021% with respect to sample concentration. The method is rapid and the resolution achieved was about 3.0. This method can be employed for the quantification of (2S, 3R) enantiomer in voriconazole drug substance.     

First stereoselective total synthesis of panaxjapyne C

The first stereoselective total synthesis of polyacetylene panaxjapyne C is described. The key reactions include regioselective opening of the epoxide and Cadiot-Chodkiewicz cross-coupling reactions. l-Ascorbic acid was used as a chiral pool material for the construction of the both terminal acetylenes.     

Transition metal mediated construction of pyrrole ring on 2,3-dihydroquinolin-4(1H)-one: synthesis and pharmacological evaluation of novel tricyclic heteroarenes

A facile two-step method for the construction of fused pyrrole ring leading to 5-substituted 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-1-ones via C-C followed by intramolecular C-N bond forming reaction is described. In vitro pharmacological evaluation and molecular modelling studies of some of the compounds synthesized are presented.     

Synthesis of the C1-C12 fragment of amphidinolide T1

A synthesis of the C1-C12 fragment of amphidinolide T1 utilising Evans’ aldol, oxy-Michael and cross metathesis reactions as the key steps is described.     

Complexes of platinum,rhodium, iridium and ruthenium with a thiosemicarbazone derived from thiophene-2-carboxaldehyde

Summary Complexes of thiophene-2-carboxaldehyde thiosemicarbazone with Ru^III, Rh^III, Ir^III and Pt^IV have been prepared and characterized by elemental analyses, molar conductance, room temperature, magnetic moments, infrared and electronic spectral studies. Probable structures for the complexes are suggested. All are diamagnetic except the Ru^III complexes and possess octahedral structures. The crystal field parameters of the complexes have also been calculated.     

Microwave-accelerated Wittig olefination of β-chloroacroleins

The first microwave assisted Wittig reactions of β-chloroacroleins with a stabilized ylide are described here. A combination of sodium ethoxide and toluene was found to be optimum and using this reaction condition a number of alkenyl-substituted benzopyran/benzo[b]oxepine/2-chromenone derivatives were prepared within few minutes. The microwave mediated process was found to be comparable with the conventional Wittig reaction in terms of product yields. All the products isolated were found to have E-geometry around the CC bond.