1,3-Dipolar cycloaddition of nitrile oxides to (R)-1-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: synthesis and antimycobacterial evaluation of novel enantiomerically pure di- and trispiroheterocycles

Enantiomerically pure (R)-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones were synthesized for the first time, and their 1,3-dipolar cycloaddition with nitrile oxides affording di- and trispiroheterocycles regio- and stereoselectively in moderate yields was investigated. These compounds were evaluated against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug-resistant M. tuberculosis (MDR-TB). Among the compounds screened, the dispiroheterocycle, namely, (5R,6R,10S)-3,9-bis(4-chlorophenyl)-10-(2,4-dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-tri-azadispiro[4.0.4.4]tetradeca-2,8-diene 5m was found to possess the maximum activity with MIC of 0.49 μM against MTB, being 9.6 and 15.6 times more potent than ciprofloxacin and ethambutol, respectively. Against MDR-TB, 5m displayed maximum activity with an MIC of 0.49 μM, with it thus being more active than rifampicin, isoniazid, ciprofloxacin and ethambutol by 7.8, 23, 77 and 124 times, respectively.     

Down-up algebras at roots of unity

In this note, we show that down-up algebras at roots of unity are maximal orders over their centers.

     

Bromodimethylsulfonium bromide (BDMS): a useful reagent for conversion of aldoximes and primary amides to nitriles

An operationally simple and high yielding procedure has been developed for the preparation of nitriles from aldoximes and primary amides using bromodimethylsulfonium bromide (BDMS) as a novel and efficient reagent in the absence of any added base or catalyst. The optimal protocol is applicable to access a wide range of cyano compounds including aromatic, heterocyclic, and aliphatic species. The conversion of aldoximes to nitriles takes place at room temperature in acetonitrile, whereas acetonitrile at reflux temperature is required for rapid conversion in the case of primary amides.     

Optical nonlinearity of organic dyes as studied by Z-scan and transient grating techniques

The excited state absorption cross-section of 5,5′-dichloro-11-diphenyl-amino-3,3′-diethyl-10, 12-ethylinethiatricarbocyanine perchlorate (IR140) have been measured by using a single beam transmission technique. Z-scan experiments have been used to find out a few nonlinear parameters. The excited state relaxation times have also been measured by using laser induced transient grating (LITG) technique.     

Stereodivergent approach to Alzheimer's therapeutic agent (R)-(−) and (S)-(+)-arundic acid employing chiral 4-pentenol derivatives as building blocks

An efficient stereodivergent total synthesis of anti-Alzheimer agent (R)-(?) and (S)-(+)-arundic acid has been achieved from both chiral and nonchiral materials. This strategy features an efficient approach to separable diastereomeric C-2 chiral 4-pentenol intermediates employing proline catalysed asymmetric α-aminooxylation and [3,3] sigmatropic Claisen rearrangement are the highlights of present synthesis.     

Single Frequency Impedance Analysis on Reduced Graphene Oxide Screen-Printed Electrode for Biomolecular Detection

A biofunctionalized reduced graphene oxide (rGO)-modified screen-printed carbon electrode (SPCE) was constructed as an immunosensor for C-reactive protein (CRP) detection, a biomarker released in early stage acute myocardial infarction. A different approach of single frequency analysis (SFA) study was utilized for the biomolecular sensing, by monitoring the response in phase angle changes obtained at an optimized frequency resulting from antigen-antibody interactions. A set of measurements were carried out to optimize a frequency where a maximum change in phase angle was observed, and in this case, we found it at around 10 Hz. The bioelectrode was characterized by contact angle measurements, scanning electron microscopy, and electrochemical techniques. A concentration-dependent response of immunosensor to CRP with the change in phase angle, at a fixed frequency of 10 Hz, was found to be in the range of 10 ng mL^?1 to 10 μg mL^?1 in PBS and was fit quantitative well with the Hill-Langmuir equation. Based on the concentration-response data, the dissociation constant (K _d) was found to be 3.5 nM (with a Hill coefficient n = 0.57), which indicated a negative cooperativity with high anti-CRP (antibody)-CRP (antigen) binding at the electrode surface. A low-frequency analysis of sensing with an ease of measurement on a disposable electroactive rGO-modified electrode with high selectivity and sensitivity makes it a potential tool for biological sensors.     

Synthesis,anti-inflammatory activities and docking studies of amide derivatives of meclofenamic acid

NSAIDs constitute a heterogeneous class of pharmacological agents widely prescribed for the treatment of inflammation, pain and edema, as well as osteoarthritis, rheumatoid arthritis and musculoskeletal disorders. This class of drugs has proved efficacious on account of their analgesic, anti-pyretic and anti-inflammatory activities, but gastrointestinal toxicity exists as the biggest problem associated with their chronic use. Many attempts have been made to structurally modify conventional NSAIDs as selective COX-2 inhibitors based on the old and still prevalent common belief that selective inhibition of COX-2 would provide safer NSAIDs. The present work thus focused on the synthesis of amide derivatives of one of the conventional non-selective NSAID, meclofenamic acid utilizing the one pot procedure involving a selective agent, bis (2-oxo-3-oxazolidinyl) phosphonic chloride. The synthesized compounds were tested for their in vivo inflammatory activity using carrageenan rat paw edema assay, and were subsequently docked on COX-2 PDB code 4COX to have better insights into their mechanism of action. The amide derivative with N-4-methoxybenzyl moiety (TSN4) proved to have anti-inflammatory potential (72.8%) better than meclofenamic acid (56.75%). This compound also docked with the highest dock score among the synthesized compounds and was found to have both hydrogen bonding with Arg120 and Tyr355 and hydrophobic interactions with Val349, Leu352, Ser353, Tyr385, Trp387, Met522, Val523, Ala527 and Ser530. N-4-methoxybenzyl amide derivative (TSN4) followed by benzyl amide derivative (TSN1) of meclofenamic acid were identified as potential anti-inflammatory compounds in both in vivo and in silico studies.     

Stereoselective Total Synthesis of Dodoneine

A simple and highly efficient stereoselective total synthesis of dodoneine ( 1 ), a naturally occurring bioactive 5,6‐dihydro‐2H‐pyran‐2‐one, was achieved. The synthesis involved Keck's asymmetric allylation, iodine‐induced electrophilic cyclization, and Grubbs' catalyzed ring‐closing metathesis as key steps.