Nano-structured polyaniline in biocatalysis: Manifesting simultaneous competence of polyaniline nanofibers and nanotubes as immobilization matrices for laccase mediated synthesis of drug intermediates.

Customized nano-biocatalysts of laccase have been made using nano-structured polyaniline viz. nano-fibers and nano-tubes, as immobilization supports and a simultaneous comparison between them has been made. Laccases are poly-phenol oxidases having tremendous utility concerning wider areas of application especially in the field of organic and drug syntheses.

Skeletal Editing via Transition-Metal-Catalyzed Nitrene Insertion.

Metal-nitrenes are valuable reactive intermediates for synthesis and are widely used to construct biologically relevant scaffolds, complexes and functionalized molecules. The ring expansion of cyclic molecules via single-nitrogen-atom insertion via nitrene or metal-nitrenoid intermediates has emerged as a promising modern strategy for driving advantageous nitrogen-rich compound synthesis. In recent years, the catalytic insertion of a single nitrogen atom into carbocycles, leading to N-heterocycles, has become an important focus of modern synthetic approaches with applications in medicinal chemistry, materials science, and industry.

KSO-Mediated Denitrogenative Formal Transformylation of Amines with Formylhydrazine in Water.

A new approach for direct formylation of various amines has been disclosed using a novel formylating agent, formylhydrazine, to afford -formylamines in significant yields with application in the gram-scale synthesis of chlorothiazide. This transformylation (transfer of a formyl group from hydrazine to amines) occurs via denitrogenation in the presence of KSO as the exclusive reagent with water as the solvent. Two reaction pathways involving extremely underexplored formyl or hemiaminal radicals have been postulated, which require further investigation.

Skeletal Editing by Hypervalent Iodine Mediated Nitrogen Insertion.

Hypervalent iodine reagents are versatile and readily accessible reagents that have been extensively applied in contemporary synthesis in modern organic chemistry. Among them, iodonitrene (ArI=NR), is a powerful reactive species, widely used for a single-nitrogen-atom insertion reaction, and skeletal editing to construct N-heterocycles. Skeletal editing with reactive iodonitrene components has recently emerged as an exciting approach in modern chemical transformation.

Intramolecular Reductive Amidation of Unactivated Esters with Nitroarenes: A Telescoped Synthesis of Tetrahydropyrrolo/Pyrido[1,2-]quinoxalinones.

A reductive amidation of unactivated esters with nitroarenes, a key step in the telescopic synthesis of tetrahydropyrrolo[1,2-]quinoxalinones and tetrahydropyrido[1,2-]quinoxalinones, is reported. The process involves an intermolecular base-mediated SAr reaction, followed by intramolecular reductive amidation employing sodium dithionite. The substrate scope coupled with the demonstration of the synthesis of pharmaceuticals is reported.

Effect of Clemizole on Alpha-Synuclein-Preformed Fibrils-Induced Parkinson's Disease Pathology: A Pharmacological Investigation.

Parkinson's disease (PD) is a neurodegenerative disorder associated with mitochondrial dysfunctions and oxidative stress. However, to date, therapeutics targeting these pathological events have not managed to translate from bench to bedside for clinical use. One of the major reasons for the lack of translational success has been the use of classical model systems that do not replicate the disease pathology and progression with the same degree of robustness.

Direct access to pyrrole anhydrides oxidative self-coupling of pyrrole carboxaldehydes.

An elegant synthesis of pyrrole-2-carboxylic acid anhydrides from pyrrole-2-carboxaldehydes using TBAI as a catalyst and -butyl hydroperoxide (TBHP) as an oxidant is described herein. Unlike the previous reports wherein pyrrole-2-carboxylic acids were invariably used, we report here for first time the oxidative self-coupling of -benzyl pyrrole-2-carboxaldehydes for the synthesis of 1-benzyl-1-pyrrole-2-carboxylic anhydrides. In addition, a one-pot synthesis of novel pyrrole-2-carboxamides from pyrrole-2-carboxaldehydes is also reported.

Dithionite-Mediated Tandem Nitro Reduction/Imine Formation/Intramolecular Cyclization for the Synthesis of Dihydro-benzothiadiazine-1,1-dioxides.

A one-pot, tandem reductive annulation of 2-nitrobenzenesulfonamides with aldehydes to the synthesis of substituted 3,4-dihydro-2-1,2,4-benzothiadiazine-1,1-dioxides in the presence of sodium dithionite (NaSO) is reported under mild conditions. The method involves in situ reduction of the nitro group followed by condensation with aldehydes to form an imine, which upon subsequent intramolecular cyclization forms the product under one-pot conditions. The protocol features use of inexpensive NaSO as the exclusive reagent, appreciable functional group tolerance, broad substrate scope, high product yields, and scalability.

Growing Utilization of Radical Chemistry in the Synthesis of Pharmaceuticals.

Our current unhealthy lifestyle and the exponential surge in the population getting affected by a variety of diseases have made pharmaceuticals or drugs an imperative part of life, making the development of innovative strategies for drug discovery or the introduction of refined, cost-effective and modern technologies for the synthesis of clinically used drugs, a need of the hour. Ever since their discovery, free radicals and radical cations or anions as reactive intermediates have captivated the chemists, resulting in an exceptional utilization of these moieties throughout the field of chemical synthesis, owing to their unprecedented and widespread reactivity. Sticking with the idea of not judging the book by its cover, despite the conventional thought process of radicals being unstable and difficult to control entities, scientists and academicians around the globe have done an appreciable amount of work utilizing both persistent as well as transient radicals for a variety of organic transformations, exemplifying them with the synthesis of significant biologically active pharmaceutical ingredients.

Divergent synthesis of pyrrole carboxamides from pyrrole carboxaldehyde and formamides/amines oxidative amidation involving pyrrole acyl radicals.

A non-traditional approach for the synthesis of pyrrole carboxamides from pyrrole carboxaldehyde and formamides or amines with catalytic amounts of BuNI and TBHP as oxidants is reported herein. The method is operationally simple providing straightforward access to primary, secondary, and tertiary pyrrole carboxamides in good to excellent yields utilizing inexpensive reagents under mild conditions. Unlike traditional amidations that involve ionic reactions, a mechanistic study of our current method unveils the involvement of 2- or 3-pyrrole acyl radicals that are otherwise rarely postulated.

Amelioration of Parkinson's disease by pharmacological inhibition and knockdown of redox sensitive TRPC5 channels: Focus on mitochondrial health.

Aims: Transient receptor potential canonical 5 (TRPC5) channels are redox-sensitive cation-permeable channels involved in temperature and mechanical sensation. Increased expression and over-activation of these channels has been implicated in several central nervous system disorders such as epilepsy, depression, traumatic brain injury, anxiety, Huntington's disease and stroke. TRPC5 channel activation causes increased calcium influx which in turn activates numerous downstream signalling pathways involved in the pathophysiology of neurological disorders.

Sulfate radical anion-induced benzylic oxidation of -(arylsulfonyl)benzylamines to -arylsulfonylimines.

A mild, operationally convenient, and practical method for the synthesis of synthetically useful -arylsulfonylimines from -(arylsulfonyl)benzylamines using KSO in the presence of pyridine as a base is reported herein. In addition, a "one-pot" tandem synthesis of pharmaceutically relevant -heterocycles by the reaction of -arylsulfonylimines, generated in situ with -substituted anilines is also reported. The key features of the protocol include the use of a green oxidant, a short reaction time (30 min), chromatography-free isolation, scalability, and economical, delivering -arylsulfonylimines in excellent yields of up to 96%.

Recent Advances On Direct Formylation Reactions.

Aldehydes serve as the key functional group in organic synthesis and are valuable intermediates. The various advanced methods of direct formylation reactions have been reviewed in this article. Overcoming the drawbacks of the traditional methods of formylation, newer methods involving homo and heterogenous catalysts, one pot reactions, solvent free techniques are elaborated, which can be performed under mild conditions and using inexpensive resources.

Decarboxylative Amidation of Aryl/Heteroarylacetic Acids via Activated Esters through Traceless α-Functionalized Benzylic Radicals.

Unlike conventional amide synthesis, a decarboxylative amidation of aryl/heteroarylacetic acids by reaction with NHS and -butyl nitrite has been reported to afford both aliphatic and (hetero)aromatic amides in satisfactory yields. Mechanistic studies revealed a previously unexplored pathway for the formation of an activated ester through the generation and subsequent reactions of traceless α-functionalized benzylic radicals, which upon subsequent one-pot reaction with amines form the amides. A gram-scale synthesis of Moclobemide indicates the practical applicability.

pH-Controlled Intramolecular Decarboxylative Cyclization of Biarylacetic Acids: Implication on Umpolung Reactivity of Aroyl Radicals.

A simple approach for the intramolecular aroylation of electron-rich arenes under mild conditions has been developed. A pH-controlled polarity umpolung strategy can be used to synthesize different fluorenones, which are important building blocks for biological applications. Unlike previous acylation reactions involving nucleophilic aroyl radicals, this approach likely relies on in situ generated electrophilic aroyl radicals.

Sulfoxylate Anion Radical-Induced Aryl Radical Generation and Intramolecular Arylation for the Synthesis of Biarylsultams.

Aryl radical generation from the corresponding aryl halides using an electron donor and subsequent intramolecular cyclization with arenes could be an important advancement in contemporary biaryl synthesis. A green and practically useful synthetic protocol to access diverse six- and seven-membered biarylsultams especially with a free NH group including demonstration of a gram-scale synthesis is reported herein. The sulfoxylate anion radical (SO), generated in situ from the reagents rongalite or sodium dithionite (NaSO), was found to be the key single electron transfer agent forming aryl radicals from aryl halides, which upon intramolecular arylation gives biarylsultams with good to excellent yields.

Diversity in Heterocycle Synthesis Using α-Iminocarboxylic Acids: Decarboxylation Dichotomy.

Despite the structural similarity with imines, α-iminocarboxylic acids have seldom been used in heterocycles synthesis. The reactions of -substituted anilines and arylglyoxylic acids in DMSO at 40 °C gave various benzo-fused five- to six-membered N-heterocycles in good to excellent yields. The reaction proceeds via intramolecular Michael addition of α-iminocarboxylic acids, generated in situ, with an -substituted nucleophile, yielding an isolable unprecedented tetrahedral carboxylic acids, which upon decarboxylation without any aid of additional reagents forms the N-heterocycles.

KSO activation by glucose at room temperature for the synthesis and functionalization of heterocycles in water.

While persulfate activation at room temperature using glucose has primarily been focused on kinetic studies of the sulfate radical anion, the utilization of this protocol in organic synthesis is rarely demonstrated. We reinvestigated selected KSO-mediated known organic reactions that invariably require higher temperatures and an organic solvent. A diverse, mild functionalization and synthesis of heterocycles using the inexpensive oxidant KSO in water at room temperature is reported, demonstrating the sustainability and broad scope of the method.

Light-assisted anticancer photodynamic therapy using porphyrin-doped nanoencapsulates.

Light activatable porphyrinic photosensitizers (PSs) are essential components of anticancer and antimicrobial therapy and diagnostic imaging. However, their biological applications are quite challenging due to the lack of hydrophilicity and biocompatibility. To overcome such drawbacks, photosensitizers can be doped into a biocompatible polymer such as gelatin and further can be used for biomedical applications.

Recent Advances in Functionalization of Pyrroles and their Translational Potential.

Among the known aromatic nitrogen heterocycles, pyrrole represents a privileged aromatic heterocycle ranging its occurrence in the key component of "pigments of life" to biologically active natural products to active pharmaceuticals. Pyrrole being an electron-rich heteroaromatic compound, its predominant functionalization is legendary to aromatic electrophilic substitution reactions. Although a few excellent reviews on the functionalization of pyrroles including the reports by Baltazzi in 1963, Casiraghi and Rassu in 1995, and Banwell in 2006 are available, they are fragmentary and over fifteen years old, and do not cover the modern aspects of catalysis.

Possible competitive modes of decarboxylation in the annulation reactions of ortho-substituted anilines and arylglyoxylates.

Annulation reactions of ortho-substituted anilines and arylglyoxylates in the presence of KSO at 80 °C under metal-free neutral conditions have been investigated, which extended a platform for the tandem synthesis of nitrogen heterocycles. While arylglyoxylic acids are known to undergo decarboxylation to form an acyl radical in the presence of KSO and used in the Minisci acylation of electron-deficient (hetero)aromatics, their reactions with electron-rich ortho-substituted anilines to form nitrogen heterocycles have recently been studied. Depending upon the experimental conditions used in the reactions, the mechanism of the formation of heterocycles involving reactions of an acyl radical or aryl iminocarboxylic acids has been postulated.

Benzylic Methylene Functionalizations of Diarylmethanes.

Diarylmethanes are cardinal scaffolds by virtue of their unique structural feature including the presence of a benzylic CH group that can be easily functionalized to generate a variety of fascinating molecules holding immense importance in pharmaceutical, agrochemical, and material sciences. While the originally developed protocols for benzylic C-H functionalization in diarylmethanes employing base-mediated and metal-catalyzed strategies are still actively used, they are joined by a new array of metal-free conditions, offering milder and benign conditions. With the recent surge of interest towards the synthesis of functionalized diarylmethanes, numerous choices are now available for a synthetic organic chemist to transform the benzylic C-H bond to C-C or C-X bond offering the synthesis of any molecule of choice.

Aroylation of Electron-Rich Pyrroles under Minisci Reaction Conditions.

The development of Minisci acylation on electron-rich pyrroles under silver-free neutral conditions has been reported featuring the regioselective monoacylation of (NH)-free pyrroles. Unlike conventional Minisci conditions, the avoidance of any acid that could result in the polymerization of pyrroles was the key to success. The umpolung reactivity of the nucleophilic acyl radical, generated in situ from arylglyoxylic acid, could help explain the mechanism of product formation with electron-rich pyrroles.