Alternative Synthesis Research Articles

Copper Catalyzed Synthesis of Heterocyclic Molecules via C-N and C-O Bond Formation under Microwaves: A Mini-Review.

Heterocyclic moieties play a significant role in the field of drug discovery. C-N and C-O bond formation reactions are the primary synthetic sequence for the generation of heterocyclic molecules. The generation of C-N and C-O bonds involves the use of mostly Pd or Cu catalysts although other transition metal catalyst's are also involved. However, in C-N and C-O bond formation reactions, several problems were faced such as catalytic systems containing costly ligands, lack of substrate scope, lots of waste generation, and high temperature conditions. So it is imperative to uncover new eco-friendly synthetic strategies. In view of enormous drawbacks, it is important to develop an alternate microwave-assisted synthesis of heterocycles via C-N and C-O bond formation, which provides a short reaction time, tolerance for functional groups, and less waste production. Numerous chemical reactions have been accelerated using microwave irradiation which provides a cleaner reaction profile, lower energy consumption, and higher yields. This review article highlights a comprehensive overview on the potential application of microwave assisted synthetic routes for the synthesis of diverse heterocycles via mechanistic pathways covering the year ranges from 2014 to 2023, along with possible biological interests.

An alternative synthesis of 3′-deoxy-3′-fluoro-d-ribofuranosyl nucleoside, an important fragment of antitumor active cyclic dinucleotide

An alternative synthesis of 3′-deoxy-3′-fluoro-d-ribofuranosyl nucleoside from d-arabinose is disclosed. Inversion of configuration at C3 on d-arabinoside promoted by DAST reagent is utilized to form lyxo-configured furanoside. After a sequence of fluorination, acidic methanolysis, triflation and displacement by -OBz. 3′-deoxy-3′-fluoro-d-ribofuranoside is obtained, which is then transformed to 1-O-benzoyl derivative. The synthesis of three 3′-deoxy-3′-fluoro-d-ribofuranosyl nucleosides, which can be served as fragment of antitumor active cyclic dinucleotide is finally completed through Vorbrüggen glycosylation .

An alternate synthesis of sporiolide B from (R)-glyceraldehyde

In this article, a novel synthetic route was described for the total synthesis of Sporiolide B from inexpensive and commercially available starting materials by a concise fourteen-step sequence in 6.50% overall yield. This convergent synthesis utilizes Grignard reaction, Asymmetric dihydroxylation, Yamaguchi macrolactonization and ring closing metathesis as the key steps.

Stigmasterol Protects Against Steatohepatitis Induced by High-Fat and High-Cholesterol Diet in Mice by Enhancing the Alternative Bile Acid Synthesis Pathway

BackgroundHepatic cholesterol accumulation is a significant risk factor in the progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis. However, the precise mechanism by which stigmasterol (STG) mitigates this process remains unclear. ObjectivesThis study aimed to investigate the potential mechanism underlying the protective effect of STG in mice with NAFLD progressing to steatohepatitis while being fed a high-fat and high-cholesterol (HFHC) diet. MethodsMale C57BL/6 mice were fed an HFHC diet for 16 wk to establish the NAFLD model. Subsequently, the mice received STG or a vehicle via oral gavage while continuing the HFHC diet for an additional 10 wk. The study evaluated hepatic lipid deposition and inflammation as well as the expression of key rate-limiting enzymes involved in the bile acid (BA) synthesis pathways. BAs in the colonic contents were quantified using ultra-performance liquid chromatography-tandem mass spectrometry. ResultsCompared with the vehicle control group, STG significantly reduced hepatic cholesterol accumulation (P < 0.01) and suppressed the gene expression of NLRP3 inflammasome and interleukin-18 (P < 0.05) in the livers of HFHC diet-fed mice. The total fecal BA content in the STG group was nearly double that of the vehicle control group. Additionally, the administration of STG increased the concentrations of representative hydrophilic BAs in the colonic contents (P < 0.05) along with the upregulation of gene and protein expression of CYP7B1 (P < 0.01). Furthermore, STG enhanced the α-diversity of the gut microbiota and partially reversed the alterations in the relative abundance of the gut microbiota induced by the HFHC diet. ConclusionsSTG mitigates steatohepatitis by enhancing the alternative pathway for BA synthesis.

The (1H-Tetrazol-1-yl)arenediazonium Salts as Convenient Reagents for Quinones Arylation: Synthesis of 1,3-Benzoxathiol-2-ones and Naphtho[2,1-d][1,3]oxathiol-2-ones Bearing (1H-Tetrazol-1-yl)phenyl Motif

A convenient two-step method for the synthesis of novel 1,3-benzoxathiol-2-ones and naphtho[2,1-d][1,3]oxathiol-2-ones bearing (1H-tetrazol-1-yl)phenyl motif was developed. As a key step of the synthesis, an arylation of quinones (1,4-benzoquinone, 1,4-naphtho-quinones) with the (1H-tetrazol-1-yl)arenediazonium salts was studied and efficient protocols were elaborated to obtain a variety of substituted ((1H-tetrazol-1-yl)phenyl) benzo/naphtho-1,4-quinones in good to excellent yields. An alternative synthesis of ((1H-tetrazol-1-yl)phenyl) naphtho-1,4-quinones via Diels-Alder reaction of tetrazolylphenyl-1,4-benzoquinones was demonstrated. The prepared benzo/naphtho-1,4-quinones readily react with thiourea at room temperature in the presence of a strong mineral acid to form intermediate isothiuronium salts, which cyclize with high yields to condense 1,3-oxathiol-2-ones under heating.

Synthesis of immunostimulatory saponins: A sweet challenge for carbohydrate chemists

Saponins are a large family of natural glycosides showing a wide range of biological activities. Current research efforts on saponins as vaccine adjuvants have been mainly focused on the development of synthetic analogs. By mimicking the immunomodulatory saponins from Quillaja saponaria (QS), less complex and readily accessible analogs have been synthesized to improve the industrial applicability and efficacy of saponins as vaccine adjuvants. Through the exploration of several structural modifications on the skeleton of QS saponins, including changes in the sugar and aglycone compositions as well as in the nature and configuration of the glycosidic bonds, structure-activity relationship (SAR) studies developed by Pr. Gin in the early 2010s were taken as a starting point for the development of a new generation of immunomodulatory candidates. In this review, the recent synthetic strategies and SAR studies of mono- and bidesmosidic QS saponins are discussed. Original concepts of vaccination including self-adjuvanticity and the development of saponin-based glycoconjugates are described. The synthesis and semi-synthesis of saponin alternatives to QS, such as Momordica saponin and onjisaponin derivatives, are also discussed in this review.

Ecofriendly hair dye extraction from wastewater pericarp processing by-products of water caltrop (Trapa quadrispinosa): Optimization and evaluation

As an alternative approach for toxicological effects of synthetic hair dyes, water caltrop (Trapa quadrispinosa) pericarp pigment extracted by 50% ethanol at 40 °C for 30 min was used as an ecofriendly and natural hair dye. Water caltrop pericarp (WCP) of seven regions were experimented to develop eco-friendly dyes intended for application in alternative chemical synthesis hair dyeing products. The results showed that the highest content of polyphenol was extracted from WCP in Jiaxing, which was used as a follow-up study. The optimization method was mordant dyeing first and then dyeing. Optimal dyeing conditions were identified as 4% Fe3+ at 25 °C with a total dyeing time of 65 min, and WCP hair dye showed better resistance to washing. The results of SEM and DSC showed that WCP hair dye could replace synthetic hair dyes and has some restorative function for damaged hair. This study provides a valuable reference for the development of more environmentally friendly hair dyes.

Life Cycle Analysis of a Green Solvothermal Synthesis of LFP Nanoplates for Enhanced LIBs in Chile.

Despite the structural and electrochemical advantages of LiFePO4 (LFP) as a cathode material, the solid-state reaction commonly used as a method to produce it at the industrial level has known disadvantages associated with high energy and fossil fuel consumption. On the other hand, solution-based synthesis methods present a more efficient way to produce LFP and have advantages such as controlled crystal growth, homogeneous morphology, and better control of pollutant emissions because the reaction occurs within a closed system. From an environmental point of view, different impacts associated with each synthesis method have not been studied extensively. The use of less polluting precursors during synthesis, as well as efficient use of energy and water, can provide new insights into the advantages of each cathode material for more environmentally friendly batteries. In this work, a solvothermal method is compared to a solid-state synthesis method commonly used to elaborate LFPs at the commercial level in order to evaluate differences in the environmental impacts of both processes. The solvothermal method used was developed considering the reutilization of solvent, water reflux, and a low thermal treatment to reduce pollutant emissions. As a result, a single high crystallinity olivine phase LFP was successfully synthesized. The use of ethylene glycol (EG) as a reaction medium enabled the formation of crystalline LFP at a low temperature (600 °C) with a nano-plate-like shape. The developed synthesis method was evaluated using life cycle analysis (LCA) to compare its environmental impact against the conventional production method. LCA demonstrated that the alternative green synthesis process represents 60% and 45% of the Resource Depletion impact category (water and fossil fuels, respectively) of the conventional method. At the same time, in the Climate change and Particular matter impact categories, the values correspond to 49 and 38% of the conventional method, respectively.

Facile and Eco-Friendly Approach To Produce Confined Metal Cluster Catalysts

Zeolite-supported metal nanocluster catalysts have attracted significant attention due to their broad application in heterogeneously catalyzed reactions. The preparation of highly dispersed metal catalysts commonly involves the use of organic compounds and requires the implementation of complicated procedures, which are neither green nor deployable at the large scale. Herein, we present a novel facile method (vacuum-heating) which employs a specific thermal vacuum processing protocol of catalysts to promote the decomposition of metal precursors. The removal of coordinated H2O via vacuum-heating restricts the formation of intermediates (metal-bound OH species), resulting in catalysts with a uniform, metal nanocluster distribution. The structure of the intermediate was determined by in situ Fourier transform infrared, temperature-programmed decomposition, and X-ray absorption spectroscopy (XAS) measurements. This alternative synthesis method is eco-friendly and cost-effective as the procedure occurs in the absence of organic compounds. It can be widely used for the preparation of catalysts from different metal species (Ni, Fe, Cu, Co, Zn) and precursors and is readily scaled-up.

Facile synthesis of porous graphite by calcium carbide and nitrogen gas for lithium-ion batteries

As a cathode material for lithium-ion batteries, porous graphite can significantly improve its high current charge-discharge performance, but the preparation of porous graphite is a challenging subject. In this study, graphite with typical mesoporous characteristics was facile synthesized by thermochemical reaction of calcium carbide with nitrogen gas. Their properties and structures were characterized, and their electrochemical properties were examined. Increasing the reaction temperature can increase the graphitization degree of the product. The product prepared at 900 °C for 3 h has high graphitization crystallinity and mesoporous structure. In addition, the PG900 exhibits high specific capacity in the range of 357–186 mAh g−1 at current rates from 0.1 C to 5 C, and thus can be ideal candidate for active materials used in lithium-ion battery. The results may imply an alternative synthesis of porous graphite, as well as an efficient approach for the high value utilization of calcium carbide.

Electrochemical Oxidative Annulation of Inactivated Alkynes for the Synthesis of Sulfonated 2H-Chromene Derivatives.

A unique, facile, and straightforward electrochemical oxidative annulation of inactivated propargyl aryl ethers with sulfonyl hydrazides leading to 3-sulfonated 2H-chromenes has been achieved. Significantly, this protocol involves a green approach that works under mild reaction conditions using a constant current in an undivided cell and is devoid of oxidants and catalysts. Notably, the process exhibited a broad scope and functional group tolerance to deliver 2H-chromenes and would represent an alternative and sustainable strategy versus conventional chromene synthesis.

Development of a Scalable Route toward an Alkylated 1,2,4-Triazol, a Key Starting Material for CXCR3 Antagonist ACT-777991

Several synthetic routes toward triazole building block 2-(3-methyl-1H-1,2,4-triazol-1-yl)acetic acid are described. The main problems of the initial synthetic route via alkylation of 3-Me-1H-1,2,4-triazole, such as poor regioselectivity, low yield, and purification by column chromatography, could be significantly improved or completely avoided in the second-generation approaches. Key concepts for the design of the alternative synthesis approaches to solve the problem of regioselectivity were the desymmetrization of 3,5-dibromo-1H-1,2,4-triazole and the de novo synthesis of the triazole core. The scalability of all routes was demonstrated on >100 g scale.

In Situ Crystallization of the Inorganic Lead-Free Halide Double Perovskite Cs2AgBiBr6 via Spray-Drying

Nontoxic, all-inorganic perovskite light absorbers have received a great deal of attention in recent years due to their potential to replace lead-containing perovskite materials in photovoltaics. Herein, the synthesis of the lead-free double perovskite Cs2AgBiBr6 as a powder, obtained via spray-drying, is reported to be capable of paving the way toward large scale production. Upon drying of the atomized precursor solution during spray-drying, the double-perovskite phase forms by in situ crystallization. The product that is obtained from spray-drying is compared to the one that is obtained from the so-called solution cooling method, which is often used for the absorber synthesis before dissolving the double perovskite powder for the thin film deposition. The absorber powder gained from the solution cooling method sets the benchmark for the spray-dried absorber powder. XRD and Raman analyses confirm the phase purity of the double perovskite, whereas UV–Vis spectroscopy confirms the desired bandgap. Furthermore, the absorber powders from both synthesis methods are successfully used to deposit and integrate absorber films in single-junction perovskite solar cells. Besides being introduced as an alternative synthesis route for the preparation of double perovskite absorber as dry powders independently from being applied onto a given substrate, the superior advantages of spray-drying compared to the conventional synthesis of the perovskite absorber via the solution cooling method are outlined: Spray-drying not only enables the synthesis of large amounts of perovskite absorber powders but also discards the usage of precarious solvents like concentrated hydrobromic acid and thus eliminates the need for extensive safety precautions. Hence, spray-drying may help the perovskite technology take the next step toward large-scale production and commercialization.

Scrutinizing the CO Chemical Capture Path in Li2MnO3 Samples with Different Microstructural Properties

Hydrothermal and ball-milling procedures combined with the solid-state reaction method were proposed as alternative synthesis routes to modify microstructural Li2MnO3 powders. All these materials were compared against Li2MnO3 prepared by following the solid-state reaction method only. To totally understand the effect of the synthesis routes proposed, the modified samples were structurally and microstructurally analyzed and subsequently subjected to the CO chemisorption process. Li2MnO3-modified samples exhibited important differences and improvements during the CO chemisorption process, in comparison to the powders obtained through the solid-state reaction method, associated with important variations on their microstructural features. Specifically, the sample prepared by the hydrothermal bottom-up approach and labeled as HSS700 showed the best CO chemisorption. This result was explained based on its crystal and particle sizes, morphology, and specific surface area. Moreover, the whole analysis performed on all the samples allowed one to determine that the solid–gas interphase controls the CO chemisorption over the CO-Li2MnO3 kinetics.

First Diels–Alder reaction of a N-nitrogen-substituted iminium ion as dienophile furnishing N-amino-substituted 1,2,5,6-tetrahydropyridines

The exploratory and preliminary work on the reaction of 1-(methoxydiphenylmethyl)-2-methyldiazene with 1,3-dienes reveals a remarkable dichotomy furnishing different heterocyclic Diels–Alder products depending on the presence or absence of water. In contrast to the acid-induced hydrolysis of the N,O-ketal starting material with 1,3-dienes furnishing 1-methyl-1,2,3,6-tetrahydropyridazines (preceding communication), the same acid-promoted reaction albeit under exclusion of water affords N-(methyleneamino)-1,2,5,6-tetrahydropyridines. The serendipitous discovery of the novel 1,2,5,6-tetrahydropyridines was corroborated by an alternative and independent synthesis providing the in situ generated formaldehyde benzophenone azine and its conjugate acid, 2-(diphenylmethylene)-1-methylenehydrazin-1-ium ion. The protonated azine serving as the putative dienophile resembles the first example of an N-nitrogen-substituted iminium ion employed as a dienophile in a bona fide normal electron-demand Diels–Alder reaction.Graphical abstract

Construction of 0D/1D CdS/g-C3N4 Z-scheme heterojunction for highly selective photocatalytic benzylamine oxidative coupling

The efficient solar-to-chemical energy conversion system is a green and cost-effective approach for producing high-value-added chemicals in chemical industry, which is highly demanded to develop. Photocatalytic C–N coupling of benzylamine into economic N-benzylidenebenzylamine is a great potential method for alternative conventional organic synthesis. In this work, a zero-dimensional/one-dimensional CdS/g-C3N4 Z-scheme heterojunction was constructed via in situ growing CdS quantum dot onto g-C3N4 nanorod surface for enhancing the spatial separation of charge carriers and maintaining the strong redox ability of the photogenerated charges and applied simultaneously in photocatalytic C–N coupling of benzylamine. This enables 20 wt% CdS/g-C3N4 to exhibit a remarkable photocatalytic performance enhancement for the production of C–N coupled product of benzylamine with the optimal yield of 199.79 μmol which is approximately 4.3 folds than those of pristine g-C3N4 under 2 h visible irradiation. Moreover, benzylamine conversion of approximately 90% within 100 h can be obtained in a gram scale-up reaction. By means of controlled photoelectric chemistry and in situ electron spin resonance spectroscopy experiments, possible spatial photogenerated charges separation and benzylamine conversion mechanisms on the Z-scheme junction were investigated in detail. This work paves a promising strategy for constructing zero-dimensional/one-dimensional Z-scheme heterojunction for the photocatalytic synthesis of high-value-added products.

Metakaolin-based geopolymer – Zeolite NaA composites as CO2 adsorbents

In this work, three metakaolin-based geopolymer matrices were prepared, varying the molar ratio Si:Al (2.0 or 1.2) and the type of cation (sodium or potassium). Starting from these matrices, geopolymer-zeolite composites were synthesized and consolidated (80 °C), incorporating a commercial sodium-based zeolite, Na4A, with the aim of producing post combustion CO2 adsorbents, since the presence of Na4A crystalline phase is desirable due to its known remarkable CO2 adsorption capacity.The sodium-based geopolymer matrix with Si:Al = 1.2 allowed the in situ nucleation of the zeolite NaA, therefore this matrix was added with different amount of synthetic zeolite Na4A to verify the total conversion of the matrix into zeolite NaA, in view of an alternative low-cost synthesis method to obtain zeolite NaA as a “solid” in a complex form.The composites were deeply characterized and lastly tested for CO2 adsorption. The geopolymer matrices act as binders allowing the shaping of zeolite and producing functional composites with mutable chemical composition, microstructure and porosity according to the starting composition. The sodium-based geopolymer zeolite composite was the best performing in term of CO2 adsorption capacity being 1.0 mmol g−1 at 0.1 bar, nearly equivalent to synthetic zeolite Na4A (1.2 mmol g−1) and close to pure zeolite Na13X (1.4 mmol g−1), the current benchmark material for carbon capture application.

The Effect of synthesis methods and comparative study of structural properties of micro and nano Ferrites

In this study, Mn(x)Zn(1-x)Fe2O4 ferrite samples with x=0.4 and 0.6 were synthesized using a solid-state method and co-precipitation method. In order to determine the effects of various concentrations (x) on the ferrite's structure, particle size, and crystalline phases, prepared samples were analysed using X-ray diffraction (XRD). The XRD patterns revealed that the synthesized samples display a single-phase cubic spinel structure.FTIR analysis showed for both synthesis method have absorption band in the range 400 to 1000 cm-1.SEM analysis shows extreme homogeneity of all the samples. EDX analysis was used to examine for Mn0.4Zn0.6Fe204,The prepared ferrites powders contain Mn, Zn, and Fe, as shown in both synthesis methods.In this approach, alternative synthesis routes for these ferrites are suggested in this study in order to get around some limitations of the traditional preparation method.

Synthesis of 5,6-Dihydrophenanthridines via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C-H Bonds.

5,6-Dihydrophenanthridines are common aza heterocycle frameworks of natural products and pharmaceuticals. Herein, we reported the first palladium-catalyzed intramolecular C-H/C-H dehydrogenative coupling reaction of two simple arenes to generate 5,6-dihydrophenanthridines. The approach features a broad substrate scope and good tolerance of functional groups, offering an efficient alternative synthesis route for important 5,6-dihydrophenanthridine compounds.

Revealing the History and Mystery of RNA-Seq.

Advances in RNA-sequencing technologies have led to the development of intriguing experimental setups, a massive accumulation of data, and high demand for tools to analyze it. To answer this demand, computational scientists have developed a myriad of data analysis pipelines, but it is less often considered what the most appropriate one is. The RNA-sequencing data analysis pipeline can be divided into three major parts: data pre-processing, followed by the main and downstream analyses. Here, we present an overview of the tools used in both the bulk RNA-seq and at the single-cell level, with a particular focus on alternative splicing and active RNA synthesis analysis. A crucial part of data pre-processing is quality control, which defines the necessity of the next steps; adapter removal, trimming, and filtering. After pre-processing, the data are finally analyzed using a variety of tools: differential gene expression, alternative splicing, and assessment of active synthesis, the latter requiring dedicated sample preparation. In brief, we describe the commonly used tools in the sample preparation and analysis of RNA-seq data.