Synthetic Scheme Research Articles

Synthetic strategies and medicinal perspectives of 4‐thiazolidinones: Recent developments and structure–activity relationship studies

AbstractThe 4‐thiazolidinone moiety is a privileged scaffold showing diversity in biological responses like antiinflammatory, antidiabetic, anticancer, antitubercular, anesthetic, hypnotic, antiviral and many more. As a result of this, researchers have been studying and synthesizing this class of heterocycles through several simple as well as complex pathways as the target scaffold for biological studies. This review recapitulates the recent advances in the chemical and biological activities of 4‐thiazolidinones that have proved to be of immense importance in the discovery and development of several molecules and, thereby, the treatment of many ailments. This study will add to previously published reviews by examining the research on various biological activities of 4‐thiazolidinones, including patents, with a focus on structure–activity relationship (SAR) investigations. Literature and patents emphasizing synthetic schemes and biological activities of 4‐thiazolidinones have covered the data in the last decade. Here, sufficient efforts have been put into place to compile the synthetic strategies, establish SARs and enlist various patents so far for this fantastic molecule. The facile synthetic schemes and a vast range of biological activity profiles possessed by this nucleus may provide researchers with new opportunities toward novel therapeutics.

Magnetic Multi-Enzymatic System for Cladribine Manufacturing.

Enzyme-mediated processes have proven to be a valuable and sustainable alternative to traditional chemical methods. In this regard, the use of multi-enzymatic systems enables the realization of complex synthetic schemes, while also introducing a number of additional advantages, including the conversion of reversible reactions into irreversible processes, the partial or complete elimination of product inhibition problems, and the minimization of undesirable by-products. In addition, the immobilization of biocatalysts on magnetic supports allows for easy reusability and streamlines the downstream process. Herein we have developed a cascade system for cladribine synthesis based on the sequential action of two magnetic biocatalysts. For that purpose, purine 2'-deoxyribosyltransferase from Leishmania mexicana (LmPDT) and Escherichia coli hypoxanthine phosphoribosyltransferase (EcHPRT) were immobilized onto Ni2+-prechelated magnetic microspheres (MagReSyn®NTA). Among the resulting derivatives, MLmPDT3 (activity: 11,935 IU/gsupport, 63% retained activity, operational conditions: 40 °C and pH 5-7) and MEcHPRT3 (12,840 IU/gsupport, 45% retained activity, operational conditions: pH 5-8 and 40-60 °C) emerge as optimal catalysts for further synthetic application. Moreover, the MLmPDT3/MEcHPRT3 system was biochemically characterized and successfully applied to the one-pot synthesis of cladribine under various conditions. This methodology not only displayed a 1.67-fold improvement in cladribine synthesis (compared to MLmPDT3), but it also implied a practically complete transformation of the undesired by-product into a high-added-value product (90% conversion of Hyp into IMP). Finally, MLmPDT3/MEcHPRT3 was reused for 16 cycles, which displayed a 75% retained activity.

Indole-Containing Natural Products 2019-2022: Isolations, Reappraisals, Syntheses, and Biological Activities.

Indole alkaloids represent a large subset of natural products, with more than 4100 known compounds. The majority of these alkaloids are biologically active, with some exhibiting excellent antitumor, antibacterial, antiviral, antifungal, and antiplasmodial activities. Consequently, the natural products of this class have attracted considerable attention as potential leads for novel therapeutics and are routinely isolated, characterized, and profiled to gauge their biological potential. However, data on indole alkaloids, their various structures, and bioactivities are complex due to their diverse sources, such as plants, fungi, bacteria, sponges, tunicates, and bryozoans; thus, isolation methods produce an incredible trove of information. The situation is exacerbated when synthetic derivatives, as well as their structures, bioactivities, and synthetic schemes, are considered. Thus, to make such data comprehensive and inform researchers about the current field's state, this review summarizes recent reports on novel indole alkaloids. It deals with the isolation and characterization of 250 novel indole alkaloids, a reappraisal of previously reported compounds, and total syntheses of indole alkaloids. In addition, several syntheses and semi-syntheses of indole-containing derivatives and their bioactivities are reported between January 2019 and July 2022.

On the inverse identification of wood elastic properties using a DIC-based FEMU approach

PurposeThis work aims to identify the linear elastic orthotropic material paramters of Pinus pinaster Ait. wood, using full-field measurements and an inverse identification strategy based on the finite element (FE) method updating technique.Design/methodology/approachCompression tests are carried out under uniaxial and quasi-static loading conditions on wood specimens oriented on the radial-tangential (RT) plane, with different grain orientations. Full-field displacements and strains are measured using digital image correlation (DIC), which are then used as a reference in the identification procedure. A FE model is implemented assuming plane stress conditions, where wood is modelled as an orthotropic homogeneous material. Based on the numerical results, a synthetic image reconstruction scheme is implemented to synthetically deform the reference experimental image, which is then processed by DIC and further compared to the experimental results.FindingsThe results for both approaches were similar when both specimen configurations were used in a single run. However, when using the DIC-based FEMU approach with the on-axis configuration, the identified modulus of elasticity in the tangential direction and shear modulus are closer to the reference values.Originality/valueThis approach ensures a fair comparison between both sets of data since the full-field strain maps are obtained through the same filter and therefore have the same strain formulation, spatial resolution and data filtering. Firstly, the identification is performed using a single configuration, either the on-axis or the off-axis specimen. Secondly, the identification is carried out by merging data from both on-axis and off-axis configurations.

Imidazoquinoxaline as a Privileged Fused Pharmacophore in Anticancer Drug Development: A Review of Synthetic Strategies and Medicinal Aspects

AbstractCancer, the uncontrolled growth of cells, is not a single but a multifaceted disorder with malignant behavior, metastasis, and invasion, medically known as malignant neoplasm. The number of cases and morbidity due to cancer is rising alarmingly worldwide, causing around 21 % annually. Imidazoquinoxaline is a privileged scaffold with a wide range of pharmacological activities that is well explored for its anticancer potential. As a synthon, imidazoquinoxaline presents a large number of possibilities for structural modifications, which have attained the attention of many researchers for the development of new anticancer molecules with diverse improved target specificity and efficiency. Development of imiquimod followed by EAPB203 and EAPB503 derivatives further enhanced the popularity of this structural pharmacophore. In this report, we have focused on the anticancer potential of newly reported imidazoquinoxaline derivatives, along with their SAR studies and therapeutic potential. We have also enlisted the synthetic schemes reported for the synthesis of imidazoquinoxaline derivatives. The lead structural features described in this review will assist the researchers in designing and developing the novel imidazoquinoxaline pharmacophore containing anticancer compounds possessing the potential to interfere with various factors or mediators which are responsible for the progression of cancer. This report will also help in identifying the potent compounds which can be further evaluated in clinical trials for the development of new anticancer drugs with minimal to no side effects.

Visualizing Small Objects Using Amplitude-Modulated Laser Light at Microwave Frequencies

We reported on laboratory imaging experiments conducted using a system that utilizes amplitude-modulated infrared laser light at microwave frequencies. With modulations ranging from 11.1 to 15.1 GHz on a 1.55 μm near-infrared laser, the phase measurements of the modulation signals revealed a target shape with sub-mm precision. We also tested whether our system is able to achieve cross-range resolution in the spot-light mode synthetic aperture scheme. With the aid of “position-compensated signal processing”, synthetic aperture images were formed successfully. According to predications based on the principle of normal synthetic aperture radar, the spatial resolutions of the images were shown to be inversely proportional to the width of the collected data placed in the wavenumber space.

Improved Synthesis of the Amine Fragment of FR901464 and Thailanstatins through the Development of a Convenient N-Detosylation Method.

FR901464 and thailanstatins are potent cytotoxic natural products that share an amine-containing tetrahydropyran ring. We previously reported the synthesis of the tetrahydropyran component. Here, we changed the protecting group for the amine from Boc to tosyl, improving yields and the time economy. A highlight of the revised synthetic scheme is the use of lithium, t-butanol, and ethylenediamine in THF (nontraditional Birch reduction conditions) for the N-detosylation.

MSP Patches Based Optimized EEG Source Localization and Validation in Visual Cortex of Human Brain

This paper is focused on optimizing EEG source localization of visual neural activities generated in the posterior lobe of the human brain. The visual and neural systems of the human brain process the captured images of faces or scenes into optical and chemical neurons in order to produce electrical potentials over the scalp surface, where EEG electrodes measure these signals to sense the underneath visual brain activity. However, it is categorically hard to localize the true neural sources in the human brain's visual cortex due to overlapping and interaction of other active areas of the lobes of the brain. Thus, a novel algorithm of MSP inversion-based Bayesian framework with varying patches for providing the optimal free energy and minimum location in the visual cortex is proposed to address this issue. This algorithm is integrated with a synthetic EEG dataset generation scheme to validate active neural sources. This proposed algorithm provides satisfactory results in terms of optimal free energy with minimum localization error and validates true active sources in the brain. The SPM12 Toolbox is applied in processing the visual EEG dataset in this research. The application of this proposed algorithm is beneficial in terms of localizing the optimum visual sources and identifying the visual disorders or diseases in the human brain.

Synthesis of 2′-O-[3-(N-methylsulfamoyl)propan-1-yl]ribothymidine as a potentially applicable 2′-modified nucleoside for antisense oligonucleotides

A synthetic scheme was developed to derive a modified ribothymidine bearing a 3-(N-methylsulfamoyl)propyl group on 2′-oxygen (TMSP). For synthesis initiation, a nucleophilic attack of 1,2-ethanediol on 5′-protected 2,2′-anhydro-ribothymidine was performed to selectively modify the 2′-position. After protection of the 3′-hydroxy group, the hydroxyethyl group was oxidized to the aldehyde, which was coupled with isobutyl (diethoxyphosphinyl)methanesulfonate through the Horner–Wadsworth–Emmons reaction to yield the sulfonate intermediate. The intermediate was further converted to the desired TMSP. Using the phosphoramidite units derived from nucleosides, we synthesized oligonucleotides incorporating TMSP. Oligonucleotides modified with TMSP were found to have duplex stability, resistance toward 3′-exonuclease digestion, and antisense activity comparable to that of the oligonucleotide modified with a previously reported 2′-O-methylcarbamoylethyl group. Based on these results and the generality of the synthetic scheme, 2′-O-sulfamoylalkyl modification is expected to be used for the modulation of the properties of oligonucleotides by changing the substituents on the nitrogen, enabling the oligonucleotides to possess suitable properties for antisense oligonucleotides.

Synthesis, Crystal Structure, and Some Transformations of 9,12-Dichloro-ortho-Carborane

Reaction of ortho-carborane with anhydrous AlCl3 in chloroform results in a mixture of 9-chloro, 9,12-dichloro, and 8,9,12-trichloro derivatives with 9,12-dichloro-ortho-carborane being the main product. Molecular crystal structure of 9,12-dichloro-ortho-carborane was determined by the single crystal X-ray diffraction. The crystal structure of 9,12-Cl2-1,2-C2B10H10 appeared to be nearly isostructural to 9,12-dibromo-ortho-carborane: the crystal packing is built of layers in which molecules are connected via weak hydrogen and halogen bonds. A synthetic scheme for preparation of the hexachloro derivative of cobalt bis(dicarbollide) Cs[8,8′,9,9′,12,12′-Cl6-3,3′-Co(1,2-C2B9H8)2] from 9,12-dichloro-ortho-carborane has been proposed.

Microwave Assisted Synthesis of a Novel Schiff Base Scaffolds of Pyrazole Nuclei: Green Synthetic Method

Aim: The research aims to develop a sustainable microwave-assisted scheme for Synthesizing 5-(benzylidene amino)-1-phenyl-1H-pyrazole-4-carbonitrile congeners. Background: 5-(benzylideneamino)-1-phenyl-1H-pyrazole-4-carbonitrile scaffolds are novel molecules having various pharmacological activities such as neurodegenerative, anti-microbial, anticancer. Schiff base congeners are considered as efficient pharmacophores for research. These activities are due to the presence of azomethine (CH=N) group in the Schiff base compounds. Objectives: To synthesise different novel Schiff base compounds of pyrazole nuclei by green chemistry with a decent yield. Methods: The 5-(benzylideneamino)-1-phenyl-1H-pyrazole-4-carbonitrile scaffolds were prepared by two-step reactions. Both steps were microwave-assisted. The first step was to synthesize 5- amino-1-phenyl-1H-pyrazole-4-carbonitrile as an intermediate compound. This compound was synthesized by using phenyl hydrazine and 2-(ethoxymethylene)malononitrile. The temperature, pressure, and time required for this reaction were 102°C, 300W, and 45 minutes respectively. In the second step, the final Schiff base congeners were attained by reacting this compound with several aromatic aldehydes. The yield, reaction condition, and time consumption were all acceptable for the green synthetic methods rather than the conventional schemes. Results: The microwave-assisted method was more efficient. The reactions were less timeconsuming, and the overall yield of the all-synthesized compounds was 75-82%. Different spectroscopic methods characterized the synthesized congeners. The IR peak is considered the main functional group (azomethine) at 1611 cm-1 wavelength. Conclusions: This microwave-assisted synthetic scheme thus appears more environmentally due to a significant reduction in organic solvents, resulting in fewer hazardous residues. Using this scheme, we prepared different Schiff base congeners with satisfactory chemical yields.

Synthesis and antimycobacterial evaluation of pyrazinamide, benzimidazole and carboxamide derivatives

AbstractDue to the unusual structure and chemical composition of the mycobacterial cell wall, it is difficult to develop effective antitubercular treatment as it leads to many antibiotics not working and preventing drug entry. It also leads to the problem of more drug resistance. Tuberculosis (TB) is still the second most contagious disease with about 33% of the world's population being affected mainly by drug‐resistant TB (MDR, XDR), chronic infections, and the combination of TB and human immunodeficiency virus (HIV). Therefore, there is an urgent need for the development of novel antitubercular drugs that will shorten the total duration of effective treatment taken under directly observed treatment, short‐course (DOTS) guidance, solve the problem of multiple drug resistance, and provide effective treatment for TB diseases. In this review, we considered various synthetic schemes of pyrazinamide, benzimidazole, and carboxamide derivatives that have antitubercular properties that can overcome the resistance to parental drugs and thus act as an effective alternative.

Three-dimensional nanoframes with dual rims as nanoprobes for biosensing

Three-dimensional (3D) nanoframe structures are very appealing because their inner voids and ridges interact efficiently with light and analytes, allowing for effective optical-based sensing. However, the realization of complex nanoframe architecture with high yield is challenging because the systematic design of such a complicated nanostructure lacks an appropriate synthesis protocol. Here, we show the synthesis method for complex 3D nanoframes wherein two-dimensional (2D) dual-rim nanostructures are engraved on each facet of octahedral nanoframes. The synthetic scheme proceeds through multiple executable on-demand steps. With Au octahedral nanoparticles as a sacrificial template, sequential processes of edge-selective Pt deposition and inner Au etching lead to Pt octahedral mono-rim nanoframes. Then, adlayers of Au are grown on Pt skeletons via the Frank-van der Merwe mode, forming sharp and well-developed edges. Next, Pt selective deposition on both the inner and outer boundaries leads to tunable geometric patterning on Au. Finally, after the selective etching of Au, Pt octahedral dual-rim nanoframes with highly homogeneous size and shape are achieved. In order to endow plasmonic features, Au is coated around Pt frames while retaining their geometric shape. The resultant plasmonic dual-rim engraved nanoframes possess strong light entrapping capability verified by single-particle surface-enhanced Raman scattering (SERS) and show the potential of nanoprobes for biosensing through SERS-based immunoassay.

Current Perspective of Synthesis of Medicinally Relevant Benzothiazole based Molecules: Potential for Antimicrobial and Anti-Inflammatory Activities.

The therapeutic potential of the majority of the marketed drugs is due to the presence of a heterocyclic nucleus, which constitutes a huge role in the field of medicinal chemistry. These heterocyclic scaffolds could act as a template in order to design potential therapeutic agents against several diseases. Benzothiazole scaffold is one of the influential heteroaromatic rings in the field of medicinal chemistry owing to its extensive pharmacological features. Herein, we have focused on the synthesis of benzothiazole-based medicinal molecules, which possess antimicrobial and anti-inflammatory activities. This review covers a systematic description of synthetic routes for biologically relevant benzothiazole derivatives in the last five years. The main aim of this study is to show the diversification of benzothiazole-based molecules into their pharmacologically more active derivatives. This review's synthetic protocols include metal-free, metal-catalyzed, and metal precursor azo dyes strategies for the development of benzothiazole derived bioactive compounds. The discussion under the various headings covers synthetic schemes and biological activities of the most potent molecules in the form of minimum inhibitory concentration.

π‐Extended Zigzag‐Shaped Diphenanthrene‐Based p‐Type Semiconductors Exhibiting Small Effective Masses

AbstractMolecular design strategy of the π‐electron core is of importance to enhance the organic semiconducting performance. In this study, diphenanthro[1,2‐b:2′,1′‐d]thiophene (DPT) as a new zigzag‐shaped sulfur‐bridged π‐electron core and its phenyl‐substituted derivative (Ph–DPT) exhibiting unique orbital configurations are reported. The DPT derivatives are readily synthesized through a versatile synthetic scheme in five steps from the commercially available dibenzothiophene. Their single‐crystal structural analyses and band calculations revealed that both DPTs form typical herringbone packing structures, which are favorable for 2D charge carrier transport, along with small effective masses. Single‐crystal‐based field‐effect transistors (FETs) of both DPT and Ph–DPT exhibit p‐type behaviors and charge‐carrier mobility up to 5.5 cm2 V–1 s–1. These results provide information that can broaden the molecular design approaches toward high‐performance organic semiconductors.

One-Pot Catalysis: A Privileged Approach for Sustainable Polymers?

Almost all aspects of daily life involve polymers in some form or the other. However, polymer production is largely based on finite feedstocks. These limitations combined with environmental concerns force us to rethink the strategies for the synthesis of these materials. As an abundant and renewable resource, biomass is composed of a very diverse range of molecules that deserve to be valorized. The development of new methods for transforming biomass into resources suitable for polymer production remains a crucial hurdle on the road to a more sustainable chemical economy. The main challenge is to design efficient and selective transformations of abundant and inexpensive raw materials into innovative polymers. For the chemical industry to meet these challenges, process intensification must play an important role in developing cleaner and more energy-efficient technologies while aiming for safer and more sustainable processes. Catalysis is an important tool to support more sustainable plastics production by being ideally efficient, practical, and versatile. In this regard, the creation of sustainable polymers through one-pot catalysis represents an exciting frontier in materials science.In this Account, we describe some of the published advances for achieving one-pot synthesis of biobased monomers and the resulting (co)polymers. These studies demonstrate that one-pot reactions can produce sustainable materials for a wide range of applications. We show that these new multistep "one-pot" approaches are very promising from an academic and industrial point of view. These synthetic schemes have indeed allowed us to investigate the formation of new polyesters, polypeptides, and poly(meth)acrylates by different polymerization mechanisms. We discuss their efficiency by highlighting their ability to perform multiple (quantitative) synthetic transformations and bond formation steps while bypassing multiple purification procedures at the same time. While enabling the development of novel polymeric structures, we demonstrate that these one-pot procedures can also contribute to reducing the environmental footprint.In light of the growing concerns for sustainable development, these procedures may therefore allow, in the near future, one to prepare sustainable polymeric materials with advanced properties through extremely simplified routes from renewable feedstocks. Among these materials, block and alternating copolymers are unique structures that can exhibit a wide range of properties. While their multistep synthesis remains a demanding process, the one-pot synthesis of these polymers is much more scalable and can create multiblock or alternating copolymers with a wide range of potential sequences. These approaches then give access to materials whose structure and functionality can be designed to suit the need.

A fast-converging scheme for the phonon Boltzmann equation with dual relaxation times

The phonon Boltzmann transport equation with dual relaxation times is often used to describe the heat conduction in semiconductor materials when the classical Fourier's law is no longer valid. For practical engineering designs, accurate and efficient numerical methods are highly demanded to solve the equation. At a large Knudsen number (i.e., the ratio of the phonon mean free path to a characteristic system length), steady-state solutions can be obtained via the conventional iterative scheme (CIS) within a few iterations. However, when the Knudsen number becomes small, i.e., when the phonon transport occurs in the diffusive or hydrodynamic regime, thousands of iterations are required to obtain converged results. In this work, a general synthetic iterative scheme (GSIS) is proposed to tackle the inefficiency of CIS. The key ingredient of the GSIS is that a set of macroscopic synthetic equations, which is exactly derived from the Boltzmann transport equation, is simultaneously solved with the kinetic equation to obtain the temperature and heat flux. During the iteration, the macroscopic quantities are used to evaluate the equilibria in the scattering terms of the kinetic equation, thus guiding the evolution of the phonon distribution function, while the distribution function, in turn, provides closures to the synthetic equations. The Fourier stability analysis is conducted to reveal the superiority of the GSIS over the CIS in terms of fast convergence in periodic systems. It is shown that the convergence rate of the GSIS can always be maintained under 0.2 so that only two iterations are required to reduce the iterative error by one order of magnitude. Numerical results in wall-bounded systems are presented to demonstrate further the efficiency of GSIS, where the CPU time is reduced by up to three orders of magnitude, especially in both the diffusive and hydrodynamic regimes where the Knudsen number is small.

Multiple and One-Pot Synthetic Strategies for Pyrimido-Thiazine and their Derivatives

Abstract: In the present era, the use of fused heterocyclic compounds has been showing considerable value in the development and designing of new drugs. Article flow through the synthetic strategies highlight the application of metal-free, visible light-mediated catalysis for the fusion of six-membered heterocyclic scaffolds containing nitrogen and sulfur heteroatoms. The power stratagem for the synthesis of diverse fused heterocyclic compounds is the sequencing of multicomponent reactions and subsequent cyclization reactions. The heterocyclic compounds containing Nitrogen and Sulphur atoms exhibit unique properties and are used as potential reactive materials in pharmacokinetic systems. These compounds can also be synthesized considering the high yield, low waste and green synthesis. The main aim of this review is to give an outlook on the synthetic feasibility of the fused heterocyclic system and to develop an innovative heterocyclic synthetic scheme that allows for different bond-forming strategies which are having a significant impact in the pharmaceutical industry, especially the pyrimido-thiazine derivatives in the future synthetic heterocyclic chemistry. The future of Heterocyclic chemistry is the development of robust synthetic routes which can generate a bulk quantity of desired products and accelerate the drug development process.

A systematic review on diverse synthetic route and pharmacological activities of benzimidazole as optimized lead

The aim of this review is to provide the systematic information of synthetic scheme and biological activity of synthesized benzimidazole derivatives. Benzimidazole is widely used lead molecule for the synthesis of various types of pharmacologically active moiety. It is heterocyclic aromatic fused colorless solid having molecular mass of 118.053 g/mol. It is basic in nature and can be served as ligand in coordination chemistry. It is bioactive compound showed various pharmacological activity till now viz. anthelmintics (albendazole, mebendazole), proton pump inhibitors (omeprazole, pantoprazole), antibiotics, antiprotozoal, antifungal, anticancer, anti-viral, anti-oxidant, anti-inflammatory etc. Various synthetic route by various methods is also already reported. Some of them are traditional convenient method, microwave reactor method, solvent free synthesis method, green synthesis method. Due to its wide variety of biological action and the similarity with biomolecule, it is frequently taken as lead for new drug discovery

Enantioselective Hydroxylation of Dihydrosilanes to Si‐Chiral Silanols Catalyzed by In Situ Generated Copper(II) Species

AbstractCatalytic enantioselective hydroxylation of prochiral dihydrosilanes with water is expected to be a highly efficient way to access Si‐chiral silanols, yet has remained unknown up to date. Herein, we describe a strategy for realizing this reaction: using an alkyl bromide as a single‐electron transfer (SET) oxidant for invoking CuII species and chiral multidentate anionic N,N,P‐ligands for effective enantiocontrol. The reaction readily provides a broad range of Si‐chiral silanols with high enantioselectivity and excellent functional group compatibility. In addition, we manifest the synthetic potential by establishing two synthetic schemes for transforming the obtained products into Si‐chiral compounds with high structural diversity. Our preliminary mechanistic studies support a mechanism involving SET for recruiting chiral CuII species as the active catalyst and its subsequent σ‐metathesis with dihydrosilanes.