Efficient One-pot Synthesis Research Articles

Efficient one-pot green synthesis of carboxymethyl cellulose/folic acid embedded ultrafine CeO2 nanocomposite and its superior multi-drug resistant antibacterial activity and anticancer activity.

Due to the prevalence of drug-resistant bacteria and the ongoing shortage of novel antibiotics as well as the challenge of treating breast cancer, the therapeutic and clinical sectors are consistently seeking effective nanomedicines. The incorporation of metal oxide nanoparticles with biological macromolecules and an organic compound emerges as a promising strategy to enhance breast cancer treatment and antibacterial activity against drug-resistant bacteria in various biomedical applications. This study aims to synthesize a unique nanocomposite consisting of CeO2 embedded with folic acid and carboxymethyl cellulose (CFC NC) via a green precipitation method using Moringa oleifera. Various spectroscopic and microscopic analyses are utilized to decipher the physicochemical characteristics of CFC NC and active phytocompounds of Moringa oleifera. Antibacterial study against MRSA (Methicillin-resistant Staphylococcus aureus) demonstrated a higher activity (95.6%) for CFC NC compared to its counterparts. The impact is attributed to reactive oxygen species (ROS), which induces a strong photo-oxidative stress, leading to the destruction of bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CFC NC are determined as 600µg/mL and 1000µg/mL, respectively. The anticancer activity against breast cancer cell resulted in the IC50 concentration of 10.8μg/mL and 8.2μg/mL for CeO2 and CFC NC respectively.The biocompatibility test was conducted against fibroblast cells and found 85% of the cells viable, with less toxicity. Therefore, the newly synthesized CFC NC has potential applications in healthcare and industry, enhancing human health conditions.

Synthesis, Spectral Characterisation, DFT Calculations, Biological Evaluation and Molecular Docking Analysis of New Mannich Compounds Derived from Cyclopentanone

This research outlines the efficient one-pot calcium chloride-catalysed synthesis of three novel Mannich bases: M1, M2 and M3. M1 and M2 resulted from the condensing of benzaldehyde with m-nitroaniline and m-bromoaniline, respectively, in conjunction with cyclopentanone. However, M3 was obtained through the reaction of p-methoxybenzaldehyde, m-bromoaniline and cyclopentanone. The isolated compounds were thoroughly characterised using elemental analysis and various analytical and spectroscopic techniques, including the determination of their melting points, electrospray mass spectrometry (ESMS), Fourier transform infrared (FTIR), electronic spectroscopy (UV-Vis), and nuclear magnetic resonance (NMR) spectroscopy (1H- and 13C-NMR). Thermal stability (TGA and DTA analysis) of the three Mannich compounds was also examined. The newly synthesised Mannich bases exhibit remarkable potential as metal ion complexing agents and as fundamental building blocks for forming small organic molecules, particularly bioactive molecules and novel ligands for coordination chemistry. In addition to their structural significance, the biological efficacy of these compounds was assessed, revealing their excellent antimicrobial properties toward bacterial and fungal species. These activities suggest their potential use in combating microbial infections. Theoretical DFT simulations employing the B3LYP functional at the 6-311++G(d,p) level provided a thorough analysis of the stability of compounds, electrical properties, and geometry. Additionally, molecular docking studies of the Mannich compounds with two protein targets, 5IQ9 and 5VBU (both relevant for drug discovery) were performed. These studies revealed that the three Mannich compounds exhibit similar binding energies and effective interaction with both the 5IQ9 and 5VBU proteins, suggesting the potential of these Mannich compounds as dual inhibitors targeting both proteins.

Atom-Efficient Synthesis of Trimethine Cyanines Using Formaldehyde as a Single-Carbon Source.

Herein, we present an innovative and atom-efficient synthesis of trimethine cyanines (Cy3) using formaldehyde (FA) as a single-carbon reagent. The widespread application of Cy3 dyes in bioimaging and genomics/proteomics is often limited by synthetic routes plagued by low atom economy and substantial side-product formation. Through systematic investigation, we have developed a practical and efficient synthetic pathway for both symmetrical and unsymmetrical Cy3 derivatives, significantly minimizing resource utilization. Notably, this approach yields water as the by-product, in alignment with sustainable chemistry principles. Moreover, the efficient one-pot synthesis facilitates the detection of intracellular FA levels, utilizing the fluorescence signal of Cy3 in live cells. It is also possible to detect endogenous FA in the intestinal tissues. We observed a significant decrease in FA in the small intestine of inflammatory bowel disease (IBD) mice as compared to healthy mice. This methodological advancement not only enhances the scope of fluorescent dye synthesis but also contributes to sustainable practices within chemical manufacturing, offering a significant leap forward in the development of environmentally friendly synthetic strategies.

Machine learning-assisted identification of potential cancer inhibitors: Multifunctional biomineralized CaCO3-polyethyleneimine nanoparticle carriers and their application in lung cancer therapy

Cancer, as a prevalent phenomenon among malignant tumors, has a late-stage diagnosis rate approaching half, significantly limiting treatment efficacy and imposing substantial physiological and psychological burdens on patients. Therefore, developing innovative therapeutic platforms that simultaneously optimize diagnostic accuracy, enhance therapeutic efficacy, and minimize side effects is a critical scientific challenge in the field of precision cancer medicine. In this study, we employed a simple and efficient one-pot synthesis method combined with polyethyleneimine (PEI)-mediated biomineralization technology to successfully prepare calcium carbonate-polyethyleneimine (CaCO3-PEI) composite nanoparticles. These nanoparticles exhibit high pH sensitivity and can rapidly degrade under the mildly acidic conditions that mimic the tumor microenvironment, providing potential for targeted tumor therapy. Subsequently, we encapsulated compound 1, which has potential for lung cancer treatment, within the CaCO3-PEI nanoparticles, successfully constructing the CaCO3-PEI@1 composite system. Structural analysis of this composite system was conducted through characterization techniques. In vitro cell experiments demonstrated that the CaCO3-PEI@1 composite system exhibited significant anticancer effects by effectively inhibiting cancer cell proliferation through the regulation of apoptosis-related protein Bax expression. This provides new insights and experimental evidence for the development of cancer treatment strategies. Based on the experiment and molecular docking identified activity against lung cancer, the compound 1 was used as the initiator for the machine learning model, and up to 10,000 episodes were generated, after thorough examination, it was found about two-thirds of the generated episodes were entirely different from each other, which demonstrated that the machine learning model was a powerful tool for designing of potential inhibitors against lung cancer.

Cofactor-dependence alteration of 7β-hydroxysteroid dehydrogenase: Enhancing one-pot synthesis efficiency of chenodeoxycholic acid to ursodeoxycholic acid through cofactor self-recycling

NAD+-dependent 7α-hydroxysteroid dehydrogenase (7α-HSDH) and NADPH-dependent 7β-hydroxysteroid dehydrogenase (7β-HSDH) are involved in the biosynthesis of chenodeoxycholic acid (CDCA) to ursodeoxycholic acid (UDCA). To realize the one-pot synthesis of CDCA to UDCA through NAD+-NADH cycling, we aimed to improve the binding ability of Hyphomicrobium sp. 7β-HSDH to NADH. The 7β-HSDH structure was modeled and some potential residues to improve NADH affinity near conserved cofactor binding regions were screened, including Ala22, Gln23, Asn24, Asp44, Leu45, and Asn46. The dominant mutant A22T/Q23E/L45A/N46E significantly enhanced the binding affinity for NADH, resulting in a 44.9-fold increase in its kcat/Km value. It increased enzymatic activity by 65.2-fold and catalyzed the synthesis of UDCA at a yield of 77.6 % with 5 g/L 7K-LCA and 12.5 mM NADH. Molecular dynamics simulations indicated increased interactions of mutated 7β-HSDH and the ligand NADH by their spatially reduced binding distance and reaction energy. The modified cofactor-dependence of 7β-HSDH realized efficient one-pot synthesis of CDCA to UDCA through strengthening cofactor-recycling and reducing the use of cofactor, achieving 90.1 % UDCA yield and 54.1 g/L/d spatiotemporal yield when coupled with 7α-HSDH with only 0.5 mM NAD+ as coenzyme. This work also supplies a universal cofactor-dependence engineering technique for homologous HSDH enzymes.

Glucose-Water Synergy: An Organocatalytic System Driven synthesis of Benzimidazolo[2,3-b]quinazolinone and Benzothiazolo[2,3-b]quinazolinone Derivatives

Introduction: A simple and efficient one-pot synthesis of quinazolinone derivatives has been developed via a multicomponent reaction (MCR) involving the condensation of dimedone, benzaldehyde, and 2-aminobenzimidazole/2-aminobenzothiazole. Method: In this work, glucose water is used as a green, reusable, environmentally benign organocatalytic solvent system to synthesize desired products. Result: The main benefits of this one-pot method include its excellent yields, less time, cost-effectiveness, atom economy, environment benign, and easy workup. Conclusion: In conclusion, we successfully developed a green protocol for the environmentally benign synthesis of benzimidazo/benzothiazolo quinazolinones using glucose water as an organocatalytic medium.

An efficient One-Pot synthesis of NaOCl mediated pyrazolopyrimidine derivatives

The discovery and success of sildenafil, widely recognized as Viagra™, represented a major progress in the treatment of erectile dysfunction (ED). Numerous approaches for synthesis of the Pyrazolo[4,3-d]pyrimidine-7-one ring have reported in the literature. However, those methods have several drawbacks, including high temperatures, low yields, the use of hazardous materials, specific oxidation protocols, long reaction times, multiple reaction steps, and expensive catalysts. To overcome these limitations, we present a simple, catalyst-free, and cost-effective one-pot synthesis of pyrazolopyrimidine derivatives with a high yield and lower reaction time using the inorganic reagent i.e., sodium hypochlorite (NaOCl). The reaction uses easily available starting materials such as 4- amino-1-methyl-3-propylpyrazole-5-carboxamide and aldehyde derivatives under moderate conditions, providing a greener alternative to typical multi-step synthesis techniques. Detailed optimization studies to afford pyrazolopyrimidine derivatives (6a-6o) show that NaOCl is a strong oxidizing agent that promotes cyclization and functionalization processes. Structures of synthesized compounds were confirmed by 1H NMR,13C NMR and HR-MS techniques.

Efficient one-pot synthesis of 1,4-disubstituted-1,2,3-triazoles catalysed by NiO/Cu2O/CuO nanocomposites under microwave irradiation

Efficient one-pot synthesis of 1,4-disubstituted-1,2,3-triazoles catalysed by NiO/Cu2O/CuO nanocomposites under microwave irradiation

Efficient one-pot synthesis of 3-arylmethyl indoles promoted by (Bu3Sn)2MoO4 as a reusable catalyst

Efficient one-pot synthesis of 3-arylmethyl indoles promoted by (Bu3Sn)2MoO4 as a reusable catalyst

NiO@HNTs-SO3H as a new heterogeneous catalyst for the green and efficient one-pot synthesis of 1-(benzothiazolylamino) methyl-2-naphthols and tetrahydrobenzo[b]pyrans

NiO@HNTs-SO3H as a new heterogeneous catalyst for the green and efficient one-pot synthesis of 1-(benzothiazolylamino) methyl-2-naphthols and tetrahydrobenzo[b]pyrans

An Indium(III) Triflate Catalyzed Simple and Efficient One-Pot Synthesis of Substituted 3,3-Diaryloxindoles and Bis(indol-3-yl) methanes from Indoles and Isatins or Aryl Aldehydes

AbstractIndium(III) triflate was found to be an efficient metal catalyst for the electrophilic substitution reaction of substituted indoles with various isatins or aryl aldehydes in acetonitrile solvent to afford the corresponding 3,3-diaryloxindoles or bis(indol-3-yl)methanes, respectively, in high yields at room temperature. This new procedure has remarkable features such as experimental simplicity, high conversions, good to excellent yields, short reaction times, and simple workup procedures

Sustainable Synthesis of Guanidine Derivatives and Computational Assessment of their Antidiabetic Efficacy.

Type 2 Diabetes Mellitus (T2DM) represents a significant and pressing worldwide health concern, necessitating the quest for enhanced antidiabetic pharmaceuticals. Guanidine derivatives, notably metformin and buformin, have emerged as pivotal therapeutic agents for T2DM management. The present study introduces an efficient one-pot synthesis method for the production of symmetrical guanidine compounds. This synthesis involves the reaction of isothiocyanates with secondary amines, employing an environmentally friendly and recyclable reagent, tetrabutylphosphonium tribromide (TBPTB). A comprehensive assessment of the biological activity of the synthesized guanidine compounds, specifically in the context of T2DM, has been rigorously conducted. Additionally, computational analyses have unveiled their substantial potential as promising antidiabetic agents. Results highlight the relevance of these compounds in the ongoing pursuit of novel therapeutic solutions for T2DM.</p>.

Cascade 1,3-Diploar Cycloaddition and Lactamization for Diastereoselective Synthesis of Pyrrolidinedione-Fused Tetrahydropyrroloisoindolones.

A cascade reaction sequence of 1,3-dipolar cycloaddition and lactamization for the synthesis of tetrahydropyrroloisoindolone derivatives is developed. This efficient one-pot synthesis generates four bonds and two heterocyclic rings in a diastereoselective manner. Only 2 equiv of H2O are produced as the side product.

Facile and an efficient one-pot synthesis of 2-arylbenzoxazoles promoted by transition metal oxide nano catalyst

The advantages and an efficient path way of process for 2-arylbenzoxazole can be obtained by transition metal oxide Nano catalyst. The transition metal nano TiO2 catalysed and a tandem reaction between substituted 2-aminophenols and substituted aromatic aldehydes to produces scaffold series of 15 smoothly forming benzo heterocycles with good to excellent yields (80-94%). The synthesized benzoxazole compounds were confirmed by FT-IR, 1H, 13CNMR, and mass spectroscopy. This article describes a one-stage coupling technique that provides a unique way to access variously functionalized benzoxazole scaffolds. This methodology consists of a one-pot combination of condensation followed by oxidative addition reactions. It was shown that nano TiO2 in ethanol encouraged the formation of 2-aryl benzoxazole scaffolds and this catalyst quickly boosted the cascade reaction that produced a variety of collections of named derivatives. These protocols are atom-economic, efficient, reusable and modular means of accessing restricted named derivatives that have a substantial substrate tolerance and over ten points of diversity.

One-pot preparation of quercetin-doxorubicin dual-drug co-loaded nanosystem for multimodal treatment of tumors

The limitations of tumor treatment have long been attributed to drug resistance and the restricted therapeutic effects of chemotherapy. This study presents a simple and efficient one-pot synthesis approach to prepare a high drug-loading composite nanoparticle PVP/Fe-DOX@QCT (PFDQ). PFDQ exhibits excellent tumor targeting properties, with sustained drug release in the acidic environment of tumors. Furthermore, loading doxorubicin (DOX) and quercetin (QCT) in PFDQ not only reduces the toxicity of DOX to healthy cells but also inhibits the function of P-glycoprotein (P-gp), thus effectively blocking drug efflux. In addition, PFDQ shows excellent photothermal properties. When combined with photothermal therapy, PFDQ can effectively achieve light-to-heat conversion, thereby exerts synergistic effects. By integrating chemotherapy (DOX and QCT) with photothermal therapy, PFDQ established a powerful multimodal anti-tumor platform.

Efficient one-pot synthesis of CO2-based functional polycarbonates combining ROCOP and ROMP

The incorporation of diverse macromolecular blocks into CO2-based polycarbonates offers a promising approach for tailoring the properties of polycarbonates for special needs. In this work, we report for the first time the synthesis and characterization of an ABA triblock copolymer polycarbonate-b-polyalkenamer-b-polycarbonate in combination of ROCOP and ROMP via a one-pot route from CO2, epoxides and cycloalkenes. Cis-2-butene-1,4-diol as the bifunctional chain transfer agent was used as a “bridge” for the combination of different blocks as well as an effective regulator for the molecular weight of the polymers. In the one-pot reaction, the conversion of cycloalkenes reached 99.9% within 0.5 h, while the conversion of CHO was initially marginal at 0.5% but gradually increased to 99.7% after 24 h. The significant discrepancy in reaction rates between the two processes enables efficient synergistic reactions within the one-pot system. Specifically, hydroxyl-telechelic polyalkenamer is initially formed via ROMP and subsequently acts as an active species for ROCOP when coordinated with the porphyrin Al catalyst. This one-pot strategy provides a unique and simple method for controllably constructing functional polycarbonates with single-modal molecular weight distributions. By integrating the advantages of polyalkenamers and polycarbonates, this approach proves to be a viable solution for addressing the unsatisfactory thermal properties of aliphatic polycarbonates.

Catalytic One-pot Solvent Free Synthesis, Biological Activity, and Docking Study of New Series of 1, 3-thiazolidine-4-one Derivatives Derived from 2- (P-tolyl) Benzoxazol-5-amine.

In this study, a simple triethylammonium salt of phosphoric acid (triethylammonium dihydrogen phosphate) (4) in the liquid state was utilized as an inexpensive, efficient one-pot three components, solvent-free synthesis of thiazolidine-4-one derivatives, with good to excellent yields. Techniques such as FT-IR, 1H-NMR, 13C-NMR, 13C-NMR-DEPT-135, and MS. were used for the structural elucidation. The high biotic efficiency of the newly obtained compounds was confirmed by in vitro antimicrobial action against Gram-positive (S. Aureus), Gram-negative bacteria (P. Aeruginosa and E. Coli) and antifungal activity (C. Albicans) via microplate titer dilution technique. Finally, a molecular docking study was performed with a resolved crystal structure of S. Aureus D-alanine alanyl carrier protein ligase (PDB ID: 7VHV). This investigation aimed to synthesize a new series of thiazolidine-4-one derivatives combined with benzoxazole moiety. Ionic liquid assistance one-pot solvent-free synthesis method used to synthesize a new series of thiazolidine-4-one derivative 10(a-e). Structural identification of new synthesis and biological evaluation via techniques of (IR, 1H-NMR, 13C-NMR, 13C-NMR-DEPT-135, and MS). Ionic liquid is utilized as an inexpensive, efficient one-pot three-component solvent-free synthesis of thiazolidine-4-one derivatives with good to excellent yields. Most of the synthesized compounds showed high biological and anti-fungal activity, in line with the docking study against mentioned microorganism and crystal structure of PDB (ID: 7VHV), respectively.

Efficient One-Pot Synthesis of Uridine Diphosphate Galactose Employing a Trienzyme System.

The limited availability of high-cost nucleotide sugars is a significant constraint on the application of their downstream products (glycosides and prebiotics) in the food or pharmaceutical industry. To better solve the problem, this study presented a one-pot approach for the biosynthesis of UDP-Gal using a thermophilic multienzyme system consisting of GalK, UGPase, and PPase. Under optimal conditions, a 2 h reaction resulted in a UTP conversion rate of 87.4%. In a fed-batch reaction with Gal/ATP = 20 mM:10 mM, UDP-Gal accumulated to 33.76 mM with a space-time yield (STY) of 6.36 g/L·h-1 after the second feeding. In repetitive batch synthesis, the average yield of UDP-Gal over 8 cycles reached 10.80 g/L with a very low biocatalyst loading of 0.002 genzymes/gproduct. Interestingly, Galk (Tth0595) could synthesize Gal-1P using ADP as a donor of phosphate groups, which had never been reported before. This approach possessed the benefits of high synthesis efficiency, low cost, and superior reaction system stability, and it provided new insights into the rapid one-pot synthesis of UDP-Gal and high-value glycosidic compounds.

An efficient one-pot synthesis of p-xylene from bio-based 2,5-hexanedione and ethanol

A brand-new p-xylene (PX) production route via 2,5-hexanedione (HDO) and ethanol was put forward. And the reaction was successfully catalyzed by organic base - tetrapropylammonium hydroxide modified HZSM-5 zeolite. Under optimum condition, the conversion of 2,5-HDO and selectivity to PX was 89.6 % and 35.2 %, respectively, much higher than the patent HZSM-5 zeolite. For comparison, PX was also produced from 2,5-dimethyfuran (2,5-DMF) and ethanol or 2,5-HDO and ethylene under the same conditions. However, the PX selectivity and yield obtained from 2,5-HDO and ethanol was much poorer than that when 2,5-DMF or ethylene as reactant due to the series competitive dehydration reactions. To investigate the relationship between catalyst properties and performance, the physicochemical properties of catalysts were comprehensively characterized by XRD, N2 adsorption-desorption isotherms, ICP, NH3/CO2-TPD, pyridine-IR, SEM, TEM and MAS NMR. Conclusion can be drawn that the appropriate acidity and hierarchical pore structure in T0.5-HZ catalyst (HZSM-5 modified by 0.5 M tetrapropylammonium hydroxide) were beneficial to high PX selectivity and yield. Among them, the acid site with weak acid site would catalyze 2,5-HDO intramolecular aldol condensation to 3-methylcyclopentenone (MCO), while strong acid site was beneficial for 2,5-DMF hydrolysis to 2,5-HDO. Thus, acid site with moderate strength was advantageous to the conversion of 2,5-HDO to 2,5-DMF. Besides, the enough amount of acid sites and suitable B/L ratio of 0.98 can satisfy the requirements of various dehydration reactions and Diels-Alder reaction between 2,5-DMF and dienophiles, enhancing PX selectivity and yield. Additionally, the hierarchical pore structure enhanced mass transfer efficiency and improved the reaction rate. The promising production for bio-based PX via 2,5-HDO and ethanol lay solid foundation for industrialized production route from lignicellulose.

Alternative and efficient one-pot three-component synthesis of substituted 2-aryl-4-styrylquinazolines/4-styrylquinazolines from synthetically available 1-(2-aminophenyl)-3-arylprop-2-en-1-ones: characterization and evaluation of their antiproliferative activities.

In this study, an alternative and efficient one-pot three-component synthesis approach to develop a new series of (E)-2-aryl-4-styrylquinazolines and (E)-4-styrylquinazolines is described. According to this approach, the target compounds were synthesized straightforward in high yields and in short reaction times from substituted 1-(2-aminophenyl)-3-arylprop-2-en-1-ones via its well-Cu(OAc)2-mediated cyclocondensation reactions with aromatic aldehydes or its well-catalyst-free cyclocondensation reactions with trimethoxy methane (trimethyl orthoformate), and ammonium acetate under aerobic conditions. This is an operationally simple, valuable, and direct method to synthesize 2-aryl- and non-C2-substituted quinazolines containing a styryl framework at C4 position from cheap and synthetically available starting materials. All the synthesized compounds were submitted to the US National Cancer Institute for in vitro screening. The bromo- and chloro-substituted quinazolines 5c and 5d displayed a potent antitumor activity against all the tested subpanel tumor cell lines with IC50 (MG-MID) values of 5.25 and 5.50 μM, and a low cytotoxic effect with LC50 (MG-MID) values of 91.20 and 84.67 μM, respectively, indicating a low toxicity of these compounds to normal human cell lines, as required for potential antitumor agents.