Divergent coupling of -alkynylnaphthols and -quinone monoketals through a Michael addition/intramolecular annulation cascade to access benzofuryl β-naphthols.

A CFOH-catalysed tandem cyclization of -alkynylnaphthols and -quinone monoketals is disclosed. The CFOH catalyst activates alkynylnaphthol to generate an all-carbon tetrasubstituted VQM by nucleophilic addition to quinone monoketal (Michael addition). Furthermore, the CFOH catalyst triggers -quinone monoketal to generate an electrophilic oxocarbenium cation to be captured by -alkynylnaphthol regiospecifically, resulting in the formation of an all-carbon tetrasubstituted VQM, followed by an intramolecular cyclization to afford a series of 1-(3-arylbenzofuran-2-yl)naphthalen-2-ols.

Diaryl Diimidazopyrimidine Derivatives as Potent Inhibitors of Influenza A Virus: Synthesis, Evaluation and Docking Studies.

In this report, we present a new series of diaryl diimidazopyrimidine derivatives 3a-m, that have been synthesized and assessed for their in vitro antiviral activity. The derivatives were prepared through a one-step reaction involving commercially available 2,4-diamino-6-chloropyrimidine and various phenacyl bromides 2a-m, leading to the formation of the desired diaryl diimidazo- pyrimidines 3a-m with good yields. In vitro evaluations against the Influenza A H1N1 strain identified compounds 3m (SI = 73) and 3b (SI = 23) as the most potent candidates.

Imidazole-1,2,4-oxadiazole-piperazine hybrids as potent anticancer agents: Synthesis, biological evaluation and molecular docking.

A series of novel imidazole integrated substituted 1,2,4-oxadiazoles coupled with piperazines were synthesized from 5-chloro-4-(p-tolyl)-1H-imidazole-2-carbonitrile through a three-step synthetic pathway, resulting in excellent yields. All 26 hybrid imidazole derivatives were purified and characterized using NMR and HRMS techniques. Their cytotoxic effects were evaluated against five distinct cancer cell lines: MDA-MB-231 (breast), MIA PaCa-2 (pancreatic), DU-145 (prostate), HEP-G2 (liver), and HCT-116 (colorectal) utilizing the SRB assay.

Synthesis of pyrano[3,2-]chromene-2,5-diones from 4-hydroxycoumarins and aminocrotonates under solvent-free conditions.

A new one-pot approach was developed for the construction of pyrano[3,2-]chromene-2,5-diones by reacting 4-hydroxycoumarins with ethyl 3-oxo-3-phenylpropanoates in the presence of ammonium salts or aminocrotonates under solvent-free conditions. The title compounds were formed by intramolecular cyclization through new C-C and C-O bonds. Structure assignment of compound 3e was confirmed by single crystal X-ray analysis.

6-aryloxy-2-aminopyrimidine-benzonitrile hybrids as anti-infective agents: Synthesis, bioevaluation, and molecular docking.

This report explores the potential of novel 6-aryloxy-2-aminopyrimidine-benzonitrile scaffolds as promising anti-infective agents in the face of the increasing threat of infectious diseases. Starting from 2-amino-4,6-dichloropyrimidine, a series of 24 compounds inspired from the antiviral drugs dapivirine, etravirine, and rilpivirine were designed and synthesized via a two-step reaction sequence in good yields. Biological testing of synthetic analogs revealed potent inhibition against both viral and tuberculosis targets.

Variable stoichiometry and a salt-cocrystal intermediate in multicomponent systems of flucytosine: structural elucidation and their impact on stability.

New cocrystals and a salt-cocrystal intermediate system involving the antifungal drug flucytosine (FCY) and various coformers including caffeic acid (CAF), 2-chloro-4-nitrobenzoic acid (CNB), hydroquinone (HQN), resorcinol (RES) and catechol (CAL), are reported. The crystal structures of the prepared multicomponent systems were determined through SC-XRD analysis and characterized by different solid-state techniques. All FCY multicomponent systems crystallize in anhydrous form with different stoichiometric ratios.

Silver-catalyzed regioselective synthesis of pyrano heterocycles: a versatile route to samoquasine A derivatives.

This study introduces a silver-catalyzed method for the efficient and regioselective synthesis of pyrano heterocycles, utilizing readily available alcohols and water as nucleophiles. The method demonstrates high efficiency, delivering excellent yields and selectivity, and is scalable to gram quantities while maintaining broad functional group tolerance. Notably, the synthesized pyrano[3,4-]quinolines were successfully transformed into diverse samoquasine A derivatives, underscoring the method's applicability in natural product synthesis.

Ag-Catalyzed Domino Decarboxylative Alkylation/Dearomative Annulation: Entry to Fused-Pyrido[4,3-]Indolones.

Here we report the development of unprecedented silver-catalyzed intramolecular annulations of -acrolyl-2-(3-indolyl) benzimidazoles with alkyl carboxylic acids to construct complex fused-pentacyclic alkaloid scaffolds. Divergent reactivities are noticed with altered groups at C2-indole of the substrate. The reaction proceeds through decarboxylative alkylation, followed by dearomative annulation in a domino manner with excellent diastereoselectivity.

Rh(III)-Catalyzed Chemoselective [4 + 2] Annulations for the Synthesis of [1,3]Oxazinoindolones: A Combined Experimental and Computational Study.

The interaction of -alkoxy-1-indole-1-carboxamides with transition metals leads to indole-fused heterocyclic scaffolds through directing group leaving/migration, [3 + 2], N-C2 [4 + 1], and [4 + 2] annulations. However, the corresponding O-C2 [4 + 2] annulation reactions have never been reported. Herein, we report the chemoselective annulation of -alkoxy-1-indole-1-carboxamides catalyzed by Rh(III), affording [1,3]oxazinoindolones through a hitherto unknown reaction pathway.

Rh(III)-Catalyzed Sequential ortho-C-H Bond Annulation and Desulfonylation of 3-Aryl-2H-benzo[e][1,2,4]thiadiazine-1,1-dioxides: Access to 1-Aminoisoquinolines.

An efficient Rh(III)-catalyzed C-H functionalization of 3-aryl-2H-benzo[e][1,2,4]thiadiazine-1,1-dioxides with diaryl and dialkyl alkynes has been developed for the first time to the synthesis of 1-aminoisoquinoline derivatives in a single step. This method involves through the formation of one C-C bond and one C-N bond followed by desulfonylation to generate a novel series of isoquinolines in good to excellent yields. This is a direct method to produce pharmaceutically more relevant scaffolds with a high functional diversity.

Synthesis of Tetrazolo[5,1-]isoquinolines via a Suzuki-Miyaura Coupling Reaction/[3 + 2] Cycloaddition Sequence.

An efficient copper-catalyzed method for the synthesis of tetrazolo[5,1-]isoquinolines has been developed starting from alkenyl-1,2-bis(boronates). The domino reaction underwent a Suzuki-Miyaura cross-coupling reaction and an azidation followed by an in situ [3 + 2] cycloaddition. Regioselective synthesis has been demonstrated by inverting the Suzuki-Miyaura cross-coupling reaction and the azidation.

Gold(I)-Catalyzed Regioselective Synthesis of Indenylidene Derivatives via 1,5-Acryl Migration.

A novel gold (I)-catalyzed synthetic strategy has been achieved for an efficient construction of indenylidene derivatives from substituted 1,6-diynes. This reaction describes the unique reactivity of gold catalysis in facilitating the intramolecular [3,3]-sigmatropic rearrangement, 5-exo dig cyclization followed by 1,5-migration of acryl group, resulting in the formation of substituted indenylidenes. Various substituted indenylidenes were successfully synthesized with up to 92 % yields.

Total Synthesis and Revision of Stereochemistry of a Natural Benzo[]isochromene Stereodiad Isolated from .

This study presents a total synthesis and revision of the stereochemical configuration of the conformationally flexible natural product benzo[]isochromene stereodiad alongside its diastereomeric counterparts. The highlights of the synthesis are the TiCl-mediated diastereoselective aldol reaction, Pd-catalyzed lactonization, and Schmidt glycosidation. Our efforts using total synthesis disclosed herein proved that a previously assigned structure required revision.

Biocatalytic enantioselective synthesis of cenobamate, an antiepileptic drug.

A green and efficient process for the synthesis of cenobamate has been accomplished in 70% yield and >99% ee through the bio-reduction of β-ketotetrazole using Daucus carota whole plant cells. The corresponding β-hydroxytetrazole was isolated in 60% yield and >98% ee. This is the first report on the biocatalytic reduction of β-ketotetrazole using plant enzymes derived from D.

6-Strand to Stable 10/12 Helix Conformational Switch by Incorporating Flexible β-hGly in the Homooligomers of Camphor Derived β-Amino Acid: NMR and X-Ray Crystallographic Evidence.

Rational design of unnatural amino acid building blocks capable of stabilizing predictable secondary structures similar to protein fragments is pivotal for foldamer chemistry/catalysis. Here, we introduce novel β-amino acid building blocks: [1S,2R,4R]exoCDA and [1S,2S,4R]endoCDA, derived from the abundantly available R(+)-camphor, which is traditionally known for its medicinal value. Further, we demonstrate that the homooligomers of exoCDA adopt 6-strand conformation, which switches to a robust 10/12-helix simply by inserting flexible β-hGly spacer at alternate positions (1 : 1 β-hGly/exoCDA heterooligomers), as evident by DFT-calculations, solution-state NMR spectroscopy and X-ray crystallography.

N-Substituted piperazine-coupled imidazo[2,1-b]thiazoles as inhibitors of Mycobacterium tuberculosis: Synthesis, evaluation, and docking studies.

An innovative series of N-substituted piperazine-linked imidazothiazole derivatives 7(a-x) were synthesized, and their antitubercular effectiveness was evaluated. A three-step reaction sequence involving the condensation of 1,3-dichloroacetone and thiourea, coupling with substituted piperazines to give the intermediates 5(a-d) and cyclization with substituted α-bromoacetophenones produced the desired imidazothiazole derivatives 7(a-x) in excellent yields. In vitro screening of new derivatives against Mycobacterium tuberculosis H37Rv resulted in 7k (minimum inhibitory concentration [MIC]: 0.

Metal-free C(sp)-H functionalization (C-C and C-N bond formation) of 1,2,3,4-tetrahydroacridines using deep eutectic solvents as catalyst and reaction medium.

Herein, we report a metal-free and efficient method for the C(sp)-H functionalization of 1,2,3,4-tetrahydroacridines at the C4-position by the addition of azodicarboxylates (C-N bond) and maleimides (C-C bond) using deep eutectic solvents (DESs) at 80 °C. The C4-functionalized 1,2,3,4-tetrahydroacridines were achieved with high atom efficiency, precise regioselectivity, and yields ranging from 70-96%. The practicality of the developed method has been demonstrated through gram-scale synthesis.

Dual gold-catalyzed regioselective synthesis of benzofulvenes 5- cyclization.

An efficient dual gold-catalyzed regioselective synthesis of benzofulvenes has been developed from substituted allyloxy 1,5-diynes 5- cyclization. In this intramolecular organic transformation a new C-C bond formation occurs and moderate to very good yields are obtained in one pot.

Radical-mediated sulfonylative/thiolative cyclization of biaryl enones to phenanthrone derivatives.

An approach for the assembly of phenanthrone derivatives bearing all carbon quaternary centres has been developed through visible light-promoted tandem sulfonylation/intramolecular-arylation of biaryl enones with sulfonyl chlorides. A series of sulfonylated 10,10-dialkylphenanthrones were obtained in good yields. In addition, the approach has been extended to thiotrifluoromethyl (SCF) and thiocyanato (SCN) radicals to obtain the corresponding phenanthrones under oxidative conditions.

Deciphering the effect of amine versus imine ligands of copper(II) complexes in 2-aminophenol oxidation.

A series of amine (1-6) and imine (5',6') based copper(II) complexes with tridentate (NNO) ligand donors were synthesized and characterized using modern analytical techniques. All the complexes were subjected to 2-aminophenol (OAP) oxidation to form 2-aminophenoxazin-3-one, as a functional analogue of an enzyme, phenoxazinone synthase. In addition, a critical comparison of the reactivity using the amine-based complexes with their respective imine counterparts was achieved in both experimental as well as theoretical studies.

Silver-catalyzed Regioselective Synthesis of N-aryl-1H-pyrazolyl-substituted Benzenesulfonamides from Ynamides and Pyrazoles.

Silver-catalyzed N-aryl-1H-pyrazolyl substituted benzenesulfonamide derivatives were obtained regioselectively from ynamides and pyrazoles. In this intermolecular organic transformation, several substituted benzenesulfonamides were obtained in good to excellent yields by forming a new C-N bond under mild reaction conditions.

Construction of Octahydro-4H-cyclopenta[b]pyridin-6-one Skeletons using Pot, Atom, and Step Economy (PASE) Synthesis.

Cascade aza-Piancatelli reaction and [3+3]/[4+2] cycloaddition reactions are carried out using the ideality principles of pot, atom, and step economy (PASE) synthesis. The reaction resulted in generation of octahydro-4H-cyclopenta[b]pyridin-6-one scaffolds. Moreover, octahydro-5,7a-epoxycyclopenta[cd]isoindol-4-one frameworks of gracilamine alkaloid and a novel decahydro-1H-dicyclopenta[cd,hi]isoindol-6-one were also realized in good yields with excellent regio- and diastereo-selectivities.

Synthesis of Fused Tetracyclic Compounds via Oxidative Annulation: Access to Copper-Catalyzed Indolo[1,2-]quinolines and to Ruthenium-Catalyzed Isoquinolin-1[2]-ones.

A facile double oxidative annulation of (en-3-yn-1-yl)phenylbenzamides was developed allowing us to synthetize fused tetracyclic compounds. Under copper catalysis, the reaction proceeds with high efficiency and leads to new indolo[1,2-]quinolines via a decarbonylative double oxidative annulation. On the other hand, under ruthenium catalysis, new isoquinolin-1[2]-ones were obtained via a double oxidative annulation.

Ir(III)-Catalyzed Dual C-H Activation of 2-Aryl Phthalazinediones and 3-Aryl-2-benzo[][1,2,4]thiadiazine-1,1-dioxides for the Construction of Spiro-Fused Cyclic Frameworks.

An Ir(III)-catalyzed double C-H activation strategy has been developed for the synthesis of highly rigid spiro frameworks by means of -functionalization of 2-aryl phthalazinediones and 2,3-diphenylcycloprop-2-en-1-ones using the Ir(III)/AgSbF catalytic system. Similarly, 3-aryl-2-benzo[][1,2,4]thiadiazine-1,1-dioxides undergo smooth cyclization with 2,3-diphenylcycloprop-2-en-1-ones to afford a diverse range of spiro compounds in good yields with excellent selectivity. Additionally, 2-arylindazoles provide the corresponding chalcone derivatives under similar reaction conditions.

Fullerene C as Photoredox Catalyst for the Synthesis of Pyrrolo[2,1-a]isoquinolines by 1,3-Dipolar Cycloaddition-Aromatization Sequence.

Herein, fullerene (C ) is introduced as an effective photoredox catalyst for the construction of a highly functionalised pyrrolo[2,1-a]isoquinoline framework by 1,3-dipolar cycloaddition-aromatisation reaction sequence. The ability of C to efficiently harvest visible light, its long-triplet state lifetime, good photostability, and strong singlet oxygen generation potential (Φ ≈1), make it an efficient photoredox catalyst. Upon photoirradiation, C promotes the formation of singlet oxygen and superoxide radical by energy transfer (EnT) and single electron transfer (SET) mechanism.