Metal-free oxidative coupling of aryl acetylene with elemental sulphur and amines: facile access to α-ketothioamides.

A simple and efficient oxidative coupling of aromatic alkynes with elemental sulphur and secondary amines has been reported. The iodine/DMSO system easily promoted the transformations, affording thioglyoxamides via C-S, C-O, and C-N bond formations. In this context, acetylenic C-H bond oxidation has occurred through iodination, leading to the desired products. Moreover, this metal-free, one-pot protocol is accomplished by using readily available starting materials, without external oxidants, and under aerobic conditions, providing a variety of α-ketothioamide compounds in moderate to good yields.

Metal-free efficient synthesis of aryl sulfonamides from N-hydroxy sulfonamide and amines.

A simple and novel approach has been developed for the synthesis of sulfonamides from N-hydroxy sulfonamide. Notably, the iodine-tert-butyl hydroperoxide (TBHP) system efficiently promoted the sulfonylation reactions of N-hydroxy sulfonamides and amines via the oxidative cleavage of an S-N bond. A variety of aryl sulfonamides were prepared in moderate to good yields using readily available starting materials and the biomass-derived 2-MeTHF solvent. The present method has the advantages of using metal-free reagents, an eco-friendly medium, cost-effective reagents, wide substrate scope, and mild conditions.

Visible-light promoted oxidative annulation of 2-naphthols with phenylglyoxal monohydrates toward hydroxy-naphthofuranone and its derivatives.

A highly efficient and innovative method involving base-mediated oxidative annulation between 2-naphthols and phenylglyoxal monohydrate under visible light irradiation has been successfully developed. This method leads to the formation of oxygen-containing heterocyclic compounds, particularly hydroxy-naphthofuranone derivatives, encompassing a unique quaternary carbon center. An X-ray diffraction study has unambiguously confirmed the structure of one such derivative. In particular, water molecules in this reaction serve various functions as a solvent, reagent, and additive, with the conversion of the process found to be influenced by the volume of water present. This atom-economical approach demonstrates tolerance for different substituents in both phenylglyoxal monohydrate and 2-naphthol, enabling the synthesis of a variety of naphthofuranones in satisfactory to good yields. The formation of a naphthofuranium cationic intermediate under acidic circumstances enables the formation of C-C or C-O bonds with a wide range of aromatic or alcoholic nucleophilic partners. Furthermore, the identification and generation of pinacol-type starting precursors from these naphthofuranone derivatives enable the synthesis of highly regioselective naphthofuran derivatives.

Cu(II)/PTABS-Promoted, Chemoselective Amination of HaloPyrimidines.

Chemoselective amination is a highly desired synthetic methodology, given its importance as a possible strategy to synthesize various drug molecules and agrochemicals. We, herein, disclose a highly chemoselective Cu(II)-PTABS-promoted amination of pyrimidine structural feature containing different halogen atoms.

A Three-Component Synthesis of Spiropyrrolines.

A rapid synthesis of medicinally important spiropyrrolines has been achieved by the reaction of 1,3-indanediones, benzaldehyde, and (1-azidovinyl)benzene under catalyst- and reagent-free conditions. This is the first report to synthesize diverse spiropyrroline compounds from readily available feedstock materials under metal-free conditions.

Four component Ugi reaction based small-molecule probes for integrated phenotypic screening.

Quorum-sensing (QS) is a cell density-dependent signaling pathway regulated by gene expression for intra- and interspecies communication. We have targeted QS activity in Pseudomonas aeruginosa, an opportunistic human pathogen that causes disease in immunocompromised patients, with a set of probes containing a variety of functional groups, including photoreactive (diazirine) and affinity (alkyne) moieties, that were synthesized using a four-component Ugi reaction (Ugi-4CR).

Ammonia synthesis by the reductive N-N bond cleavage of hydrazine using an air-stable, phosphine-free ruthenium catalyst.

The development of an effective molecular catalyst to reduce hydrazine efficiently to ammonia using a suitable reductant and proton source is demanding. Herein, an unprecedented air-stable, phosphine-free ruthenium complex is used as a potent catalyst for hydrazine hydrate reduction to generate ammonia using SmI2 and water under ambient reaction conditions. Maximizing the flow of electrons from the reductant to the hydrazine hydrate via the metal centre results in a greater yield of ammonia while minimizing the evolution of H2 gas as a competing product.

In-vitro anticancer evaluation of newly designed and characterized tri/tetra-substituted imidazole congeners- maternal embryonic leucine zipper kinase inhibitors: Molecular docking and MD simulation approaches.

Our cascading attempt to develop new potent molecules now involves designing a series of imidazole derivatives and synthesizing two sets of 2,4,5- tri-substituted (4a-4d) and 1,2,4,5-tetra-substituted (6a-6d) imidazole by the principle of Debus-Radziszewski multicomponent synthesis reaction. The structures of the obtained compounds were confirmed by 1H/13C NMR, FT-IR, elemental analysis, purity and the retention time was analyzed by HPLC. Based upon the binding affinity in the molecular docking studies, we have synthesized different imidazole derivatives from which compound 6c have been found to show more anti-proliferative activity by inducing apoptosis at a higher rate than the other compounds corroborating the in-silico prediction. The structure and crystallinity of compound 4d have been confirmed by single XRD analysis. The synthesized molecules were screened for their in vitro anti-cancer properties in triple negative breast cancer cell line (MDA-MB-231), pancreatic cancer cell lines (MIA PaCa-2) and oral squamous cell carcinoma cell line (H357) and results indicated that all the compounds inhibited the cell proliferation in a concentration-dependent manner at different time points. The compounds 4b and 6d were found to be effective against the S. aureus bacterial strain whereas only compound 4d fairly inhibited the fungal strain of T. rubrum with a MIC 12.5 µg/mL. Molecular docking study reveals good interaction of the synthesized compounds with known target MELK involved in oncogenesis having high binding profiles. The lead compound 6c was further analyzed by the detailed molecular dynamics study to establish the stability of the ligand-enzyme complex.

Synthetic Strategies of N-Heterocyclic Olefin (NHOs) and Their Recent Application of Organocatalytic Reactions and Beyond.

N-heterocyclic olefin (NHO) derivatives have an electron-rich as well as highly polarized carabon-carbon (C=C) double bond because of the electron-donating nature of nitrogen and sulphur atoms. While NHOs have been developing as novel organocatalysts and ligands for transition-metal complexes in various organic compound syntheses, different research groups are currently interested in preparing imidazole and triazolium-based chiral NHO catalysts. Some of them have been used for enantioselective organic transformations, but were still elusive. N-heterocyclic olefins, the alkylidene derivatives of N-heterocyclic carbenes (NHC), have shown promising results as effective promoters for numerous organic syntheses such as asymmetric catalysis, hydroborylation, hydrosilylation, reduction, CO2 sequestration, alkylation, cycloaddition, polymerization and the ring-opening reaction of aziridine and epoxides, esterification, C-F bond functionalization, amine coupling, trifluoromethyl thiolation, amination etc. NHOs catalysts with suitable structures can serve as a novel class of Lewis/Bronsted bases with strong basicity and high nucleophilicity properties.These facts strongly suggest their enormous chemical potential as sustainable catalysts for a wide variety of reactions in synthetic chemistry. The synthesis of NHOs and their properties are briefly reviewed in this article, along with a summary of the imidazole and triazole core of NHOs' most recent catalytic uses.

Emerging evidence-based innovative approaches to control catheter-associated urinary tract infection: a review.

Healthcare settings have dramatically advanced the latest medical devices, such as urinary catheters (UC) for infection, prevention, and control (IPC). The continuous or intermittent flow of a warm and conducive (urine) medium in the medical device, the urinary catheter, promotes the formation of biofilms and encrustations, thereby leading to the incidence of CAUTI. Additionally, the absence of an innate immune host response in and around the lumen of the catheter reduces microbial phagocytosis and drug action. Hence, the review comprehensively overviews the challenges posed by CAUTI and associated risks in patients' morbidity and mortality. Also, detailed, up-to-date information on the various strategies that blended/tailored the surface properties of UC to have anti-fouling, biocidal, and anti-adhesive properties to provide an outlook on how they can be better managed with futuristic solutions.

Cu(II)/PTABS-Promoted, Regioselective SNAr Amination of Polychlorinated Pyrimidines with Mechanistic Understanding.

Regioselective amination of polyhalogenated heteroarenes (especially pyrimidines) has extensive synthetic and commercial relevance for drug synthesis applications but is plagued by the lack of effective synthetic strategies. Herein, we report the Cu(II)/PTABS-promoted highly regioselective nucleophilic aromatic substitution (SNAr) of polychlorinated pyrimidines assisted by DFT predictions of the bond dissociation energies of different C-Cl bonds. The unique reactivity of Cu(II)-PTABS has been attributed to the coordination/activation mechanism that has been known to operate in these reactions, but further insights into the catalytic species have also been provided.

Copper-catalysed chemoselective C-OH bond activation of N-benzoyl cytosine: facile access to 2-(dimethylamino)pyrimidine.

A novel method for the direct amination of N-benzoyl cytosine has been developed, giving access to 2-(dimethylamino)pyrimidine derivatives. A copper(II) catalyst and tert-butyl hydroperoxide easily promote the selective amination process that proceeds via C-OH bond activation. This practical approach can utilize different formamide molecules, N,N-dimethylformamide and N,N-diethylformamide, as efficient amino (-NMe2, -NEt2) sources. Moreover, the facile nature of the procedure, its broad tolerance of aliphatic and aromatic substrates, the high yields and ease of separation of the products, and the fact that it can be conducted under aerobic conditions are all notable advantages of the present protocol.

Copper catalysed oxidative cascade deamination/cyclization of vinyl azide and benzylamine for the synthesis of 2,4,6-triarylpyridines.

A highly efficient one-pot method for the synthesis of 2,4,6-triaryl pyridines has been developed via cascade deamination and annulation. Copper triflate and molecular iodine easily promoted the oxidative cyclization reaction of vinyl azide and benzylamine to access a wide variety of substituted pyridine substrates under an oxygen atmosphere. The presence of benzyl amine enables the cyclization process by providing the aryl functionality and the nitrogen source. Moreover, a broad range of substrates with good functional group tolerance, avoidance of external oxidants, excellent product yields, operational simplicity and mild conditions are the notable advantages of the present protocol.

Multi-functional approach in the design of smart surfaces to mitigate bacterial infections: a review.

Advancements in biomedical devices are ingenious and indispensable in health care to save millions of lives. However, microbial contamination paves the way for biofilm colonisation on medical devices leading to device-associated infections with high morbidity and mortality. The biofilms elude antibiotics facilitating antimicrobial resistance (AMR) and the persistence of infections. This review explores nature-inspired concepts and multi-functional approaches for tuning in next-generation devices with antibacterial surfaces to mitigate resistant bacterial infections. Direct implementation of natural inspirations, like nanostructures on insect wings, shark skin, and lotus leaves, has proved promising in developing antibacterial, antiadhesive, and self-cleaning surfaces, including impressive SLIPS with broad-spectrum antibacterial properties. Effective antimicrobial touch surfaces, photocatalytic coatings on medical devices, and conventional self-polishing coatings are also reviewed to develop multi-functional antibacterial surfaces to mitigate healthcare-associated infections (HAIs).

Cascade Nucleophilic Addition-Cyclic Michael Addition of Arynes and Indoles Bearing Michael Acceptor: A Strategy to Construct Pyrroloacridines and Study of Their Physicochemical Properties.

A facile synthetic approach to 6H-pyrrolo[3,2,1-de]acridines has been developed by using cascade N-nucleophilic addition-cyclic Michael addition process of arynes and indoles substituted with Michael acceptors under metal-free conditions. Additionally, photophysical studies of a few of the newly synthesized pyrroloacridine compounds indicated good fluorescence emission properties.

I2/TBHP-mediated oxidative cascade cyclization of vinyl azide and benzylamine to construct 2,5-disubstituted oxazoles.

A one-pot facile synthesis of disubstituted oxazoles has been achieved from vinyl azide and benzylamine. A coherent mixture of iodine and tert-butyl hydroperoxide (TBHP) efficiently promoted oxidative cascade cyclization to construct 2,5-disubstituted oxazoles under aerobic conditions. Notably, the oxidative cyclization involves feasible C(sp3)-functionalization with the elimination of the azide group as the intermediate step. In consequence, the consecutive C-N and C-O bond formations lead to a variety of disubstituted oxazole derivatives. Moreover, the one-pot methodology features a metal-free strategy, readily available reagents, shorter times, good yields, and mild reaction conditions.

Pd-catalyzed homo-coupling of benzofurans: one-pot synthesis of diverse 3,3'-bisbenzofurans.

An efficient and one-pot synthesis of 3,3'-bisbenzofuran derivatives has been developed. The protocol involved the use of a Pd catalyst and Cu(OAc)2 along with molecular oxygen as the oxidant to afford bisbenzofurans via a dehydrogenative homo-coupling reaction. The reaction exhibited good functional group/heterocycle tolerance and is amenable for gram scale synthesis.

Rapid plugged flow synthesis of nucleoside analogues via Suzuki-Miyaura coupling and heck Alkenylation of 5-Iodo-2'-deoxyuridine (or cytidine).

Nucleosides modification via conventional cross-coupling has been performed using different catalytic systems and found to take place via long reaction times. However, since the pandemic, nucleoside-based antivirals and vaccines have received widespread attention and the requirement for rapid modification and synthesis of these moieties has become a major objective for researchers. To address this challenge, we describe the development of a rapid flow-based cross-coupling synthesis protocol for a variety of C5-pyrimidine substituted nucleosides. The protocol allows for facile access to multiple nucleoside analogues in very good yields in a few minutes compared to conventional batch chemistry. To highlight the utility of our approach, the synthesis of an anti-HSV drug, BVDU was also achieved in an efficient manner using our new protocol. Supplementary Information: The online version contains supplementary material available at 10.1007/s41981-023-00265-1.

Zinc-catalyzed transamidation and esterification of N-benzoyl cytosine via C-N bond cleavage.

We have utilized N-benzoyl cytosine for efficient transamidation and esterification via catalytic C-N bond cleavage. The one-pot strategy involves the reaction of secondary amide with various aliphatic or aromatic amines and alcohols in the presence of zinc triflate and DTBP, affording diverse amides and esters in excellent yields.

Binary to ternary drug-drug molecular adducts of the antihypertensive drug ketanserin (KTS) with advanced physicochemical properties.

Focusing on a reliable supramolecular synthon approach, novel molecular salts of the antihypertensive medication ketanserin (KTS) with aromatic carboxylic acid derivatives (benzoic acid (BA), 2-hydroxybenzoic acid (2-HBA), and 2,5-dihydroxybenzoic acid (2,5-DHBA)) are reported. Binary salts of KTS with the respective salt former were obtained via solvent-assisted grinding followed by solution crystallization. Salt production was confirmed through crystal structure investigations that revealed proton transfer from the carboxylic acid group of the salt former to the piperidine nitrogen atom of KTS. A rigorous investigation of the crystal packing of novel binary salts of KTS inspired the construction of ternary adducts, and a ternary crystalline product was subsequently identified using milrinone (MLN), another cardiotonic drug. According to our knowledge, this is the first instance of a dual-drug ternary co-crystal combining both antihypertensive drugs. In order to evaluate the impacts of co-crystallization on the in vitro release behaviour of binary and ternary adducts, solubility tests for the cocrystal were carried out under a variety of physiological pH conditions. The results indicate that, in contrast to the parent drug and binary adducts, the solubility rate of the ternary adducts is significantly increased. Finally, the stability of the synthesised adduct was evaluated under a range of conditions, including temperature (40 ± 1 °C), humidity (90% ± 5% RH, 25 °C) and various solvents media, and it was established that they have good stability. We anticipate that the present findings will work with a wide range of medication combinations, providing a potential new approach to create multi-drug systems for cardiovascular disease.