Metal-Free Visible-Light Catalytic Deoxygenation of Azaaryl N-Oxides: Harnessing Photons for Efficient Greener Synthesis.

Regio- and chemo-selective functionalization of electron deficient azaarenes often required their transformations to corresponding N-oxides and subsequent removal of oxygen after functionalization to get back the desired substituted azaarenes. An efficient metal-free visible-light photo-redox catalytic deoxygenation of N-oxides of azaheterocyclic compounds has been developed using acridinium based organo-photocatalyst in blue LED light. High efficiency and mildness of this methodology has been demonstrated through higher deoxygenation yield of wide variety of azaheterocyclic N-oxides with reactive functional groups. Robustness of the photocatalytic reduction has been demonstrated through easy scaling-up of the reaction to gram level without much change in the reaction yield.

A Carbohydrate-based Synthetic Approach to Diverse Structurally and Stereochemically Complex Chiral Polyheterocycles.

Chiral polyheterocycles are one of the most frequently encountered scaffolds in natural products and in current drugs repertoire. A carbohydrate-based diversity oriented synthetic (DOS) approach has been employed for gaining access to many structurally diverse and stereochemically complex rigid polyheterocyclic molecules with multiple chiral hydroxyl groups to enhance aqueous solubility. Inexpensive chiral pool of D-Glucose has been judiciously exploited to get access of complex chiral polyheterocyclic structures using inexpensive, common achiral reagents and domino-Knoevenagel hetero-Diels-Alder (DKHDA) reaction as one of the key synthetic tools. Stereochemistry of newly generated stereocenters of polycyclic structures are unambiguously determined through NMR and X-ray crystallographic study. A chemoinformatic comparison (PCA and PMI) with 40 branded blockbuster drugs showed that newly generated polyheterocycles have good three-dimensional scaffold diversity and most of these pass the Lipinski filter of drug-likeness.

Targeting the Trypanothione Reductase of Tissue-Residing Leishmania in Hosts' Reticuloendothelial System: A Flexible Water-Soluble Ferrocenylquinoline-Based Preclinical Drug Candidate.

Since inception, the magic bullets developed against leishmaniasis traveled a certain path and then dropped down due to either toxicity or the emergence of resistance. The route of administration is also an important concern. We developed a series of water-soluble ferrocenylquinoline derivatives, targeting Leishmania donovani, among which CQFC1 showed the highest efficacy even in comparison to other drugs, in use or used, both in oral and intramuscular routes. It did not induce any toxicity to splenocytes and on hematopoiesis, induced protective cytokines, and did not hamper the drug-metabolizing enzymes in hosts. It acts through the reduction and the inhibition of parasites' survival enzyme trypanothione reductase of replicating amastigotes in hosts' reticuloendothelial tissues. Unlike conventional drugs, this molecule did not induce the resistance-conferring genes in laboratory-maintained resistant L. donovani lines. Experimentally, this easily bioavailable preclinical drug candidate overcame all of the limitations causing the discontinuation of the other conventional antileishmanial drugs.

Hydrazine functionalized probes for chromogenic and fluorescent ratiometric sensing of pH and F-: experimental and DFT studies.

Two novel hydrazine based sensors, BPPIH (N1,N3-bis(perfluorophenyl)isophthalohydrazide) and BPBIH (N1',N3'-bis(perfluorobenzylidene)isophthalohydrazide), are presented here. BPPIH is found to be a highly sensitive pH sensor in the pH range 5.0 to 10.0 in a DMSO-water solvent mixture with a pKa value of 9.22. Interesting optical responses have been observed for BPPIH in the above mentioned pH range. BPBIH on the other hand turns out to be a less effective pH sensor in the above mentioned pH range. The increase in fluorescence intensity at a lower pH for BPPIH was explained by using density functional theory. The ability of BPPIH to monitor the pH changes inside cancer cells is a useful application of the sensor as a functional material. In addition fluoride (F-) selectivity studies of these two chemosensors have been performed and show that between them, BPBIH shows greater selectivity towards F-. The interaction energy calculated from the DFT-D3 supports the experimental findings. The pH sensor (BPPIH) can be further interfaced with suitable circuitry interfaced with desired programming for ease of access and enhancement of practical applications.

Synthesis and in vitro antiviral evaluation of 4-substituted 3,4-dihydropyrimidinones.

A series of 4-substituted 3,4-dihydropyrimidine-2-ones (DHPM) was synthesized, characterized by IR, 1H NMR, 13C NMR and HRMS spectra. The compounds were evaluated in vitro for their antiviral activity against a broad range of DNA and RNA viruses, along with assessment for potential cytotoxicity in diverse mammalian cell lines. Compound 4m, which possesses a long lipophilic side chain, was found to be a potent and selective inhibitor of Punta Toro virus, a member of the Bunyaviridae. For Rift Valley fever virus, which is another Bunyavirus, the activity of 4m was negligible. DHPMs with a C-4 aryl moiety bearing halogen substitution (4b, 4c and 4d) were found to be cytotoxic in MT4 cells.

Colorimetric and fluorimetric response of Schiff base molecules towards fluoride anion, solution test kit fabrication, logical interpretations and DFT-D3 study.

Two newly synthesized Schiff base molecules are herein reported as anion sensors. -NO2 substituted receptor (P1) is comparatively more acidic and can sense F(-), OAc(-) and H2PO4(-), whereas -CN substituted receptor (P2) is less acidic and is selective for F(-) only. Reversible UV-Vis response for both receptors with F(-) can mimic multiple logic gate functions, and several complex electronic circuits based on XNOR, XOR, OR, AND, NOT and NOR logic operations with 'Write-Read-Erase-Read' options have been executed. Interesting 'turn on and off' fluorescence responses were noticed for the receptors with F(-). Intracellular F(-) detection as a diagnosis of non-skeletal fluorosis was successful using a fluorescence microscope with Candida albicans (prokaryotic cell, a diploid fungus) and pollen grains of Tecoma stans (eukaryotic cell) incubated in 10(-6) M fluoride-contaminated hand-pump water collected from Bankura, West Bengal, India. Furthermore, a solution test kit was fabricated for easy and selective detection of F(-) in an aqueous solvent.

Sequential ring-closing metathesis and nitrone cycloaddition on glucose-derived substrates: a divergent approach to analogues of spiroannulated carbanucleosides and conformationally locked nucleosides.

The carbohydrate-derived substrate 3-C-allyl-1,2:5,6-di-O-isopropylidene-alpha-D-allofuranose was judiciously manipulated for preparing suitable synthons, which could be converted to a variety of isoxazolidino-spirocycles and -tricycles through the application of ring-closing metathesis (RCM) and intramolecular nitrone cycloaddition (INC) reactions. Cleavage of the isoxazolidine rings of some of these derivatives by transfer hydrogenolysis followed by coupling of the generated amino functionalities with 5-amino-4,6-dichloropyrimidine furnished the corresponding chloropyrimidine nucleosides, which were elaborated to spiroannulated carbanucleosides and conformationally locked bicyclo[2.2.1]heptane/oxa-bicyclo[3.2.1]octane nucleosides. However, use of higher temperature for the cyclization of one of the chloropyrimidines led to the dimethylaminopurine analogue as a sole product, formed via nucleophilic displacement of the chloro group by dimethylamine generated from DMF.