Shivaputra A. Patil

A convenient, efficient and reusable N-heterocyclic carbene-palladium(II) based catalyst supported on magnetite for Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions

In the present work, a new magnetic nanoparticle supported N-heterocyclic carbene-palladium(II) (NO2-NHC-Pd@Fe3O4) nanomagnetic catalyst was synthesized by a facile multistep synthesis under aerobic conditions using inexpensive chemicals. The NO2-NHC-Pd@Fe3O4 nanomagnetic catalyst was characterized by various analytical techniques such as attenuated total reflectance infrared spectroscopy (ATR-IR), inductively coupled plasma-atomic emission spectroscopy (ICP-AES), energy-dispersive X-ray spectroscopy (EDS), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA) and Brunauer–Emmett–Teller surface area analysis (BET). The synthesized NO2-NHC-Pd@Fe3O4 nanomagnetic catalyst showed excellent catalytic activity in both Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions for various substrates under mild reaction conditions. Recovery of the NO2-NHC-Pd@Fe3O4 nanomagnetic catalyst from the reaction mixture was easily accomplished by applying an external magnet. The recovered NO2-NHC-Pd@Fe3O4 nanomagnetic catalyst exhibited very good catalytic activity up to seven recycles in Suzuki–Miyaura and five recycles in Mizoroki–Heck cross-coupling reactions without considerable loss of its catalytic activity.

Magnetic Nanoparticle-Supported N-Heterocyclic Carbene-Palladium(II): A Convenient, Efficient and Recyclable Catalyst for Suzuki-Miyaura Cross-Coupling Reactions

A new magnetic nanoparticle-supported N-heterocyclic carbene-palladium(II) nanomagnetic catalyst was synthesized and appropriately characterized using attenuated total reflectance infrared spectroscopy (ATR-IR), ultraviolet–visible spectroscopy (UV–Visible), inductively coupled plasma-atomic emission spectroscopy (ICP-AES), energy-dispersive X-ray spectroscopy (EDS), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA) and Brunauer–Emmett–Teller surface area analysis (BET). The nanomagnetic catalyst was used as convenient and efficient catalyst for the Suzuki–Miyaura cross-coupling reaction of various aryl bromides/chlorides/iodide with phenylboronic acid. The effects of varying solvents, bases, temperature, time and catalytic ratios on the performance of the Suzuki–Miyaura cross-coupling reaction were investigated. The notable advantages of this heterogeneous nanomagnetic catalyst are excellent yields, mild reaction conditions, short reaction times and easy work-up. Moreover, the new nanomagnetic catalyst could be easily recovered with an external magnet and could be reused at least five times without loss of its catalytic activity.Graphical Abstract

Medicinal applications of (benz)imidazole‐ and indole‐based macrocycles

Macrocyclic chemistry is one of the emerging research areas in the chemical science. Macrocyclic compounds continue to attract significant attention due to their numerous possible applications particularly in the areas like biology, catalysis and industry. This review article summarizes the developments and advances in synthesis and medicinal applications of macrocyclic compounds derived from (benz)imidazole‐ and indole‐based heterocycles. Important medicinal applications of (benz)imidazole‐ and indole‐based macrocycles include antimicrobial and anticancer activities. The representative lead compounds in each series of macromolecules have been discussed. All these initial lead breakthroughs help validate the great potential of (benz)imidazole‐ and indole‐based macrocyclic compounds as a class of effective medicinal agents.

Microwave-assisted synthesis of chromenes: biological and chemical importance

Chromenes constitute chemically important class of heterocyclic compounds having diverse biological and chemical importance. Development of environmentally benign, efficient and economical methods for the synthesis of chromenes remains a significant challenge in synthetic chemistry. The synthesis of chromenes, therefore, has attracted enormous attention from medicinal and organic chemists. Researchers have embraced the concepts of microwave (high speed) synthesis to produce biologically and chemically important chromenes in a time sensitive manner. This review will summarize the recent biological applications such as anticancer, antimicrobial, neurodegenerative and insecticidal activity of new chromenes prepared via microwave irradiation. The development of new methodologies for the synthesis of chromenes including green chemistry processes has also been discussed.

Recent developments in biological activities of indanones

Indanone is one of the privileged structures in medicinal chemistry and its commonly associated with various pharmacologically active compounds. The indanone moiety is found in several natural compounds and also, it can be used as intermediate in the synthesis of many different types of medicinally important molecules. Among the medicinally important indanones, the most significant drug probably is donepezil (IV), an acetylcholinesterase (AChE) inhibitor, which has been approved by the US Food and Drug Administration for the treatment of Alzheimers disease (AD). Along with donepezil, the indanone moiety can be seen in a number of other pre-clinical and clinical candidates which belong to different categories with diverse therapeutic activities. In summary, the present review article encompasses the recent biological applications such as antialzheimer, anticancer, antimicrobial and antiviral activity of various indanone derivatives.

Imidazoquinolines: Recent Developments in Anticancer Activity

Cancer remains one of the unsolved diseases of todays advanced drug discovery world even though it is known to humans for centuries. There is continued effort to discover new chemotherapeutic agents to improve the outcome of cancer patients. Small-molecule agonists at tolllike receptor 7 and 8 (TLR7/8) have recently generated renewed interest in cancer research owing to their profound antitumoral activity. TLR-7/8 agonist imidazoquinolines (Imiquimod, and Resiquimod) and dual inhibitor of phosphoinositide 3-kinase and mammalian target of rapamycin (NVP-BEZ235) have emerged as clinically important candidates for treating cancers. This article reviews briefly the synthesis, structure-activity relationship (SAR) and biological activities of clinically studied imidazoquinolines along with novel emerging preclinical imidazoquinolines for the anticancer activity.

Non-symmetrically p-nitrobenzyl- and p-cyanobenzyl-substituted N-heterocyclic carbene-silver(I) complexes: synthesis, characterization and antibacterial studies

Abstract Various nitro/nitrile-functionalized benzimidazol-2-ylidene carbene complexes of silver(I) (7a–d and 11a–d) were synthesized by combination of 1-allyl/1-isopropyl/1-sec-butyl/1-isopentyl-3-(nitro/cyano-benzyl)-3H-benzimidazol-1-ium hexafluorophosphate (6a–d and 10a–d) with silver(I) oxide in acetonitrile. The compounds were characterized by 1H, 13C NMR, FT-IR, mass spectrometry, and elemental analysis. Additionally, the in vitro antibacterial activity of the N-heterocyclic carbene (NHC) precursors (6a–d and 10a–d) and their corresponding NHC-silver(I) complexes (7a–d and 11a–d) were investigated against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli using the qualitative Kirby-Bauer disk diffusion method. All the NHC-silver(I) complexes exhibited medium-to-high antibacterial activity with areas of clearance ranging from 12 mm to 21 mm, while the NHC precursors were inactive against both strains of bacteria.

Novel 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents

Liver fibrosis is a critical wound healing response to chronic liver injury such as hepatitis C virus (HCV) infection. If persistent, liver fibrosis can lead to cirrhosis and hepatocellular carcinoma (HCC). The development of new therapies for preventing liver fibrosis and its progression to cancer associated with HCV infection remains a critical challenge. Identification of novel anti-fibrotic compounds will provide opportunities for innovative therapeutic intervention of HCV-mediated liver fibrosis. We designed and synthesized a focused set of 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents. Liver fibrosis assays demonstrated that the compounds 3a and 3c show inhibitory activity towards human hepatic stellate cells (LX2) activation at 10μM. The HCV NS3 and NS5A proteins in HCV subgenome-expressing cells were also significantly reduced in cells treated with 3a and 3c, suggesting the possible inhibitory role of the compounds in HCV translation/replication activities. We have also examined the reactivity of these compounds with medicinally-relevant metal compounds such as platinum and gold. The reactivity of these complexes with metals and during Mass Spectrometry suggests that CS bond cleavage is relatively facile.

Understanding the structure and reactivity of the C–S linkage in biologically active 5-arylthio-5H-chromenopyridines

Molecules based on the 5-arylthio-5H-chromenopyridine structure have been studied for a variety of medicinal applications, including liver fibrosis. We have recently found that the C–S linkage can be cleaved with Pt(II) and Au(I), something that was not previously recognized. In this current work, we examine the structure, properties, and reactivity of 5-arylthio-5H-chromenopyridines using spectroscopy, crystallography, reactivity, density functional theory (DFT) calculations, and electrochemistry. We report the crystal structures of 5-arylthio-5H-chromenopyridines, as well as their DFT-calculated structures and electronic structures. The DFT calculations help to explain the electronic properties of these complexes, such as the observation that “soft” metals cleave the C–S bond. We find that the arylthio group is a good leaving group on these molecules due to the stability of the carbocation that is formed, and can be removed via reduction with NaBH4. Methoxy-substituted chromenopyridines were found to be viable at inhibiting liver fibrosis. These results will help inform the biological studies with these compounds to determine method of action and enhance development of new drug molecules with increased stability and activity based on the 5H-chromenopyridine scaffold.

Magnetic Nanoparticles Supported Carbene and Amine Based Metal Complexes in Catalysis

Catalysis is one of the hottest research topics in chemistry. In recent years, metal complexes attracted great interest as catalysts towards various types of organic reactions. However, these catalysts, in most cases, suffer from the deficits during their recovery, recycling and the difficulty in separation of catalysts from the products. Therefore, the design and synthesis of recoverable and recyclable catalyst is very important aspect in catalysis. The aim of this review article is to highlight the speedy growth in the synthesis and catalytic applications of magnetic nanoparticles (Fe3O4, MNPs) supported N-heterocyclic carbene (NHC) and amine based metal complexes in various organic reactions. Furthermore, these catalysts can be easily separated from the reaction media with the external magnet and reused various times without a substantial loss of catalytic activity.