Synthesis Of Scaffolds Research Articles

Review of application of the I2 and dimethyl sulfoxide combined reagent system to aryl methyl ketones for diverse transformations

The synthesis of small molecules and complex scaffolds is one of the most important topics in organic synthesis.

The Michael donor-acceptor reactivity of curcumins in the synthesis of diverse multi-functional scaffolds.

Curcumin is a key constituent of turmeric with a variety of biological activities. From a chemical point of view, curcumin contains different functional groups that can undergo multiple transformations such as Michael addition, cycloaddition, click reaction, polymerisation, etc. Among these, Michael-type reactions under benign conditions constitute a captivating domain of curcumin's reactivity. To the best of our knowledge, no review focusing on the Michael donor-acceptor reactivity of curcumins has been published to date. Herein, we have compiled the chemistry of curcumins with respect to their chemical synthesis, biosynthesis, and involvement in chemical transformations, especially in Michael additions with advances in mechanistic aspects and understanding.

Design and synthesis of fluorine aromatic scaffolds containing drugs approved by the US FDA from 2002 to 2022

There are totally 93 fluorine aromatic scaffolds containing drugs approved by U.S. Food and Drug Administration from 2002 to 2022. The proportion of drugs containing fluorinated aromatic skeleton in approved drugs is increasing in recent ten years, which indicates the unique and important attributes of the fluorine atom. The introduction of fluorinated fragments into molecules can influence structure conformation, intrinsic potency and selectivity and pharmacokinetic properties productively. Additionally, 18F has been applied as a significant and useful positron emission tomography isotope for in vivo imaging technology. This review is mainly concentrated on the application and synthesis methods of 93 fluorine aromatic scaffolds containing drugs approved by the US FDA from 2002 to 2022. We hoped that this deep insight perspective into the synthetic methods for the delivery of these fluorine aromatic scaffolds containing drugs could offer practical and creative inspirations for the application and development of fluorine atom in new drug discovery.

Transition-metal-free [3 + 2] cycloaddition of C,N-cycloazomethylimines with in situ formed isocyanates from dioxazolones: a facile synthesis of triazolinones

A novel strategy for synthesizing triazolinone with C,N-cycloazomethylimine and dioxazolone has been developed, in which the isocyanate formed in situ from dioxazolone is employed for cyclization instead of the widely used N-acyl nitrene.

Lignin-cellulose complexes derived from agricultural wastes for combined antibacterial and tissue engineering scaffolds for cutaneous leishmaniasis wounds.

Bacterial infections in wounds significantly impair the healing process. The use of natural antibacterial products over synthetic antibiotics has emerged as a new trend to address antimicrobial resistance. An ideal tissue engineering scaffold to treat infected wounds should possess antibacterial properties, while simultaneously promoting tissue regrowth. Synthesis of hydrogel scaffolds with antibacterial properties using hemp shive (HT1/HT2) lignin, sugarcane bagasse (SCB) lignin and cellulose was carried out. All lignin samples had low molecular weights and were constituted of G-type β-5 dimers, linked by β-O-4 bonds, as determined by MALDI-TOF-MS. Hemp lignin was more cytotoxic to mouse fibroblasts (L929) compared to SCB lignin. All lignin samples demonstrated antibacterial properties against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis, with greater efficiency against Gram-negative strains. 3D hydrogels were engineered by crosslinking SCB lignin with SCB cellulose in varying weight ratios in the presence of epichlorohydrin. The stiffness of the hydrogels could be tailored by varying the lignin concentration. All hydrogels were biocompatible; however, better fibroblast adhesion was observed on the blended hydrogels compared to the 100% cellulose hydrogel, with the cellulose : lignin 70 : 30 hydrogel showing the highest L929 proliferation and best antibacterial properties with a 24-hour bacterial growth reduction ranging from 30.8 to 57.3%.

Diversity-oriented synthesis of indole-fused scaffolds and bis(indolyl)methane from tosyl-protected tryptamine.

An efficient, diversity-oriented synthesis of indole-1,2-fused 1,4-benzodiazepines, tetrahydro-β-carbolines, and 2,2'-bis(indolyl)methanes was established starting from tosyl-protected tryptamine. These diverse privileged skeletons were controllably constructed by adjusting different hydride donors and Brønsted acids. A variety of indole-1,2-fused 1,4-benzodiazepines were facilely accessed using benzaldehydes bearing cyclic amines as hydride donors via a cascade N-alkylation/dehydration/[1,5]-hydride transfer/Friedel-Crafts alkylation sequence. The reaction site could be switched when benzaldehydes bearing an alkoxy moiety as hydride donors were used for the generation of tetrahydro-β-carbolines. On the other hand, the switchable synthesis of 2,2'-bis(indolyl)methanes could be achieved as well by applying p-TsOH·H2O as a catalyst. The reactions feature mild conditions, simple and practical operation, excellent efficiency and the use of EtOH as a green solvent. Using the concept of diversity-oriented, reagent-based synthesis, the inexpensive feedstock tryptamine was efficiently converted to three different types of privileged scaffolds, which facilitates rapid compound library synthesis for accelerating drug discovery.

Synthesis of quinazolinone scaffolds via a zinc(II)-stabilized amidyl radical-promoted deaminative approach.

Herein, we report a solely ligand centered redox controlled protocol, utilizing a bench stable zinc compound, for the efficient coupling of o-amino amides/esters with nitriles to afford diverse quinazolinone scaffolds and their synthetic utility was showcased via post-modification to access therapeutically relevant compounds. Importantly, mechanistic probes established the reaction pathway that proceeds via aminyl radical.

Dearomative spirocyclization of ynamides.

Spiro N-heterocycles, particularly aza-spiro piperidines, have shown significant promise in pharmaceutical applications due to their ability to enhance physicochemical properties. Despite their potential, the preparation of these complex structures poses significant challenges. To address this, we propose a one-pot dearomative spirocyclization reaction of ynamides. This method involves a copper-catalyzed carbomagnesiation reaction, achieving chemo-, regio-, and stereoselective formation of vinyl metal intermediates. Upon the addition of a Lewis acid, these intermediates undergo a regioselective nucleophilic dearomatization event, facilitating the synthesis of diverse aza-spiro dihydropyridine scaffolds with multiple functional handles. Various Grignard reagents, diverse ynamides, and acylating reagents have been explored. A subsequent hydrogenation reaction provides access to both partially and fully reduced spirocyclic frameworks, broadening the scope of spirocyclic structures with potential medicinal applications.

Synthesis of cis-fused cyclopentenone-pyrrolidine scaffolds via sequential aza-Piancatelli and Conia-ene type reactions in one pot.

A novel one-pot protocol that enables sequential execution of an aza-Piancatelli rearrangement and a Conia-ene type reaction has been developed under Lewis acid catalysis. Here, a combination of B(C6F5)3 and Cu(OTf)2, triethylamine, and triphenylphosphine yielded a wide range of cis-fused cyclopentenone-pyrrolidine scaffolds in one pot with good yields and diastereoselectivity.

Improved synthesis of antiplasmodial 4-aminoacridines and 4,9-diaminoacridines.

Acridines are one of the most important nitrogen-containing heterocycle systems and have many applications in the therapeutic field. However, the synthesis of acridine-based scaffolds is not always straightforward. Herein, we report the optimization of two multi-step synthetic routes towards 4,9-diaminoacridines and 4-aminoacridines, which have shown promising antiplasmodial properties. The improved synthesis pathways make use of greener, simpler, and more efficient methods, with less reaction steps and increased overall yields, which were doubled in some cases. These are impactful results towards future approaches to the chemical synthesis of acridine-based compounds.

Recent advancement in the synthesis of quinoline derivatives via multicomponent reactions.

The synthesis of quinoline derivatives through multicomponent reactions (MCRs) has emerged as an efficient and versatile strategy in organic synthesis. MCRs offer the advantage of constructing complex molecular architectures in a single step, utilising multiple starting materials in a convergent manner. This review provides an overview of recent advancements in the field of quinoline synthesis via MCRs. Various MCRs, such as the Povarov reaction, the Gewald reaction, and the Ugi reaction have been successfully employed for the synthesis of diverse quinoline scaffolds. These methodologies not only showcase high atom economy but also allow the incorporation of structural diversity into the final products. The versatility of MCRs enables the introduction of functional groups and substitution patterns tailored to specific applications. This review highlights the significance of quinoline derivatives in medicinal chemistry, materials science, and other interdisciplinary areas. The continuous innovation and development of novel MCR-based approaches for quinoline synthesis hold great promise for the rapid and efficient generation of valuable compounds with a wide range of biological and physicochemical properties.

Direct photochemical intramolecular [4 + 2] cycloadditions of dehydrosecodine-type substrates for the synthesis of the iboga-type scaffold and divergent [2 + 2] cycloadditions employing micro-flow system.

Photocyclisation reactions offer a convenient and versatile method for constructing complex polycyclic scaffolds, particularly in the synthesis of natural products. While the [2 + 2] photocycloaddition reaction is well-established and extensively reported, the [4 + 2] counterpart via direct photochemical means remains challenging and relatively unexplored. In this work, we devised the rapid assembly of the iboga-type scaffold through photochemical intramolecular Diels-Alder reaction using a common biomimetic dehydrosecodine-type intermediate having vinyl indole and dihydropyridine (DHP) sub-units. Exploiting a micro-flow system, the medicinally important iboga-type scaffold was obtained up to 77% yield under mild, neutral conditions at room temperature. This study demonstrated the site-selective activation of the DHP moiety by direct UV-LED irradiation, eliminating the need for external photocatalysts or photosensitisers and showing good tolerance to a wide range of stabilised dehydrosecodine-type substrates. By adjusting the spatial arrangement of the DHP ring and the vinyl indole group, this versatile photochemical approach efficiently facilitates both [4 + 2] and [2 + 2] cyclisations, assembling architecturally complex multicyclic scaffolds. Precise photoactivation of the DHP subunit, generating short-lived biradical species, enabled the new way of harnessing the hidden but innately pre-encoded reactivity of the polyunsaturated dehydrosecodine-type intermediate. These photo-mediated [4 + 2] cyclisation and divergent [2 + 2] cycloadditions are distinct from biosynthetic processes, which are mainly mediated through concerted thermal cycloadditions.

Copper supported modified magnetic carrageenan as a bio-based catalyst for the synthesis of novel scaffolds bearing the 1,2,3-triazole unit through the click reaction.

The ongoing work delineates the design of a novel library of 1,2,3-triazole-attached phenylacetamides through molecular hybridization of propargyl and phenylacetamide derivatives. Copper-supported modified magnetic carrageenan serves as a green heterogeneous catalyst, ensuring high yield, efficient reaction times, high atom economy, utilization of an environmentally friendly catalyst from a natural source, and a straightforward workup procedure. The successful synthesis of the catalyst is confirmed and evaluated using various analytical techniques, while the synthetic compounds are characterized through 1H NMR and 13C NMR.

Highly efficient, catalyst-free, one-pot sequential four-component synthesis of novel spiroindolinone-pyrazole scaffolds as anti-Alzheimer agents: in silico study and biological screening.

Alzheimer's disease is a neurodegenerative disorder that impacts memory, thinking, and behavior, and currently, there is no effective cure available for its treatment. This study explored a one-pot strategy for synthesizing spiroindolinone-pyrazole derivatives through a sequential four-component condensation reaction. These derivatives were further investigated for their potential as anti-Alzheimer's disease agents. The developed synthetic procedure provides remarkable advantages, including a clean reaction profile, abundant starting materials, operational simplicity, and easy purification without traditional methods with good to excellent yields (84-96%). Next, the biological potencies of the newly synthesized spiroindolinone-pyrazole derivatives against AChE and BChE as Alzheimer's disease-related targets were determined. Also, the kinetic study and cytotoxicity of the most potent derivative were investigated. Furthermore, molecular docking and molecular dynamics evaluations were performed employing in silico tools to investigate the interaction, orientation, and conformation of the potent analog over the active site of the enzyme.

Green design and synthesis of some novel thiazolidinone appended benzothiazole-triazole hybrids as antimicrobial agents.

The global increase in bacterial resistance poses a significant threat, jeopardizing the effectiveness of antibiotics. Therefore, the development of new and efficient antimicrobial agents is pre-dominant. Taking this into consideration, in the present study, we designed and reported the facile synthesis of two novel series benzothiazole-triazole and thiazolidinone-appended benzothiazole-triazole hybrids using a molecular hybridization approach in a one-pot process. The synthesized compounds were tested for microbial growth inhibition against bacterial and fungal strains. Among all the synthetics, compounds derived from methoxyphenyl and heteroaromatic ring substitutions exhibited promising inhibitory activity. The current investigation has emphasized that benzothiazole-triazole hybrids incorporating thiazolidinone can be a promising and potent category of molecules with potential biological activities. This sustainable and eco-friendly protocol involves the metal-free, catalyst-free synthesis of bioactive scaffolds, which merges broad tolerance for functional groups with a short reaction time, resulting in good to excellent yields.

Stereoselective synthesis of gem-dihalopiperidines via the halo-aza-Prins cyclization reaction: access to piperidin-4-ones and pyridines.

An efficient methodology for the synthesis of 4,4-dihalopiperidine derivatives in excellent yields has been developed using N-(3-halobut-3-en-1-yl)-4-methylbenzenesulfonamide and an aldehyde catalyzed by In(OTf)3. The reaction involves an initial formation of a six-membered carbocation via the aza-Prins cyclization reaction followed by a nucleophilic attack by a halide ion to give 4,4-dihalopiperidine. The dihalopiperidine is converted to tetrahydropiperidinone using Ac2O/Et3N in DCM/H2O (1 : 1). It is also utilized for the synthesis of pyridine scaffolds by treatment with DBU. Furthermore, the dihalopiperidine is transformed to its enol ether derivatives using KOH in alcohol.

Development of novel transition metal-catalyzed synthetic approaches for the synthesis of a dihydrobenzofuran nucleus: a review.

The synthesis of dihydrobenzofuran scaffolds bears pivotal significance in the field of medicinal chemistry and organic synthesis. These heterocyclic scaffolds hold immense prospects owing to their significant pharmaceutical applications as they are extensively employed as essential precursors for constructing complex organic frameworks. Their versatility and importance make them an interesting subject of study for researchers in the scientific community. While exploring their synthesis, researchers have unveiled various novel and efficient pathways for assembling the dihydrobenzofuran core. In the wake of extensive data being continuously reported each year, we have outlined the recent updates (post 2020) on novel methodological accomplishments employing the efficient catalytic role of several transition metals to forge dihydrobenzofuran functionalities.

Access to distal biaxial atropisomers by iridium catalyzed asymmetric C-H alkylation.

Distal biaxial atropisomers are typical structures in chiral catalysts and ligands and offer a wide variety of applications in biology and materials technology, but the development of efficient synthesis of these valuable scaffolds is still in great demand. Herein, we describe a highly efficient iridium catalyzed asymmetric C-H alkylation reaction that provides a range of new distal biaxial atropisomers with excellent yields (up to 99%) and stereoselectivity (up to 99% ee and essentially one isomer). Based on this unprecedented strategy, a polycyclic skeleton with five successive chiral centers as well as C-C and C-N (or N-N) two distal chiral axes was created successfully in mild circumstances. In addition, the optically pure products bearing fluorophores show circular polarized luminescence (CPL) properties, being potential candidate materials for CPL applications.

Amide-derived enols in enol-Ugi reactions: expanding horizons for peptidomimetic scaffold synthesis.

A highly efficient enol-Ugi reaction of β,β-diketoamides has been developed using a novel non-heterocyclic amide-stabilised enol. This approach enables a broad reaction scope, affording β-enaminoamide peptidomimetics with constrained conformations due to CH-π interaction and C(sp3)H⋯O hydrogen bonding. Notably, the use of a five-membered cyclic enol is crucial for achieving stable products in excellent yields. This work highlights the potential of the enol-Ugi reaction for constructing diverse peptidomimetic scaffolds.

Sustainable Fabrication of NiCuFe2O4 Nanosphere: A Highly Effective Palladium-Free Heterogeneous Catalyst for Biaryl Scaffold Synthesis

In this work, a noble metal‐free and recyclable NiCuFe2O4 nanoparticle was developed via a one-pot co-precipitation approach. The synthesized nanoparticle was characterized by various sophisticated techniques such as SEM, EDX,...