Good Yields Research Articles

Optimization and Effect of Substituents on the Transformation of 3-(Substituted acetoxy)azetidin-2-ones to Chiral 3-Hydroxyazetidin-2-ones, Molecular Docking and Enantiomeric Excess Determination

Abstract: The enantioselective synthesis of chiral cis-3-hydroxyazetidin-2-ones mediated by Porcine Pancreatic Lipase (PPL) via hydrolysis of cis-3-(chloro acetoxy) azetidin-2-ones in the presence of a phosphate buffer (0.1M, pH = 7.2) in acetonitrile at a temperature range of 25-35 °C was optimized. Under the optimized reaction conditions, the influence of various electron withdrawing/donating/neutral groups on ester functionality of cis-3-(substituted acetoxy)azetidin-2- ones towards hydrolysis was extensively studied, and the bromoacetoxy, propanyloxy, and formyloxy groups provided moderate to good yields of 90%, 91%, and 81%, respectively. Moreover, the chiral cis-3-hydroxyazetidin-2-ones underwent acetylation, and their enantiomeric excess was assessed using the 1H NMR technique, employing chiral shift reagents. To gain insights into the active sites of the biocatalyst, molecular docking studies of compounds 5(a-i) with pancreatic lipase (PDB ID: 1LBS) were carried out. Additionally, the proposed interaction of substituents with the biocatalyst established the absolute stereochemistry of the target chiral cis-3-hydroxyazetidin-2-ones using Seebach's model in comparison to Jone's models.

Synthesis of 6H-Chromeno[4,3-b]quinolin-7-ylphosphonates through Three Component Phosphonylation of Coumarin Carbaldehyde and Their Antimicrobial and Photophysical Properties.

Organophosphorylated coumarin derivatives were synthesized by a three-component reaction of 4-chloro-3-formylcoumarin, aromatic amines, and dialkyl phosphite in the presence of ZnCl2. This process includes the formation of C(sp3)-P and C(sp2)-N bonds in one pot. The modular scope of the reaction allowed rapid access to a variety of 6H-chromeno[4,3-b]quinolin-7-ylphosphonate derivatives in good yields. Furthermore, photophysical studies of the products revealed their stimulating fluorescence properties.

Ni2MnAl Heusler Alloy Nanoparticles for Chemoselective Hydrogenation of Nitro Compounds

Despite immense interest for years in Heusler alloys as magnetoelastic materials, their application in heterogeneous catalysis has only recently been explored. We report the development of highly active, robust and magnetically separable Ni2MnAl Heusler alloy nanoparticles as a heterogeneous catalyst for hydrogenation of aliphatic and aromatic nitro compounds to the corresponding amines. The easily synthesizable Ni2MnAl nanoparticles are thermally and chemically robust and exhibited excellent chemoselectivity in the hydrogenation of a range of aliphatic and aromatic nitroarenes, including those bearing functional groups sensitive to reduction, such as alkene, bromo, iodo, carbonyl and cyano, yielding the respective functionalized amines in good yields. Moreover, this solid catalyst is magnetically separable from the reaction mixture and could be recycled and reused at least 10 times without any loss in catalytic activity. The mechanism of the Ni2MnAl Heusler alloy nanoparticles catalyzed nitro reduction was studied by various spectroscopy and control experiments and kinetics. Our work opens a new avenue of developing heterogeneous earth‐abundant metal catalysis for economic and environment‐friendly synthesis of fine chemicals owing to their straightforward synthesis and tunable composition from base‐metals and their diverse structure and properties with their high surface area, thermal and chemical stability, excellent chemoselectivity, magnetic separability and recyclability.

Asymmetric 1,4-Addition of Diarylphosphine Oxides to α, β-Unsaturated 2-Acyl Imidazoles.

Here we introduce a metal-free, catalytic and enantioselective strategy from α,β-unsaturated 2-acyl imidazoles to the chiral phosphorous 2-acyl imidazoles. Interestingly, this methodology was catalyzed by the classical and commercial oxazaborolidine under mild conditions. This strategy features a wide range of substrates scope with good yields and excellent enantioselectivities. The possible mechanism further suggests the key of this reaction through the cleavage of diarylphosphine oxides using Frustrated Lewis Pairs theory.

Convergent Paired Electrolysis for [3+2] Cycloaddition of Azidotrimethylsilane with N-Heterocycles.

A widely used method to obtain tetrazoles is through the azide and nitrile [3+2] cycloaddition. However, this process often involves using non-recyclable transition metals or Lewis acid catalysts and stoichiometric amounts of oxidants and additives, which reduces atom efficiency. We have discovered a convergent paired electrochemical reaction to perform this cycloaddition reaction, without the need for metal catalysts or oxidants. This tetrazolation strategy uses azidotrimethylsilane (TMSN3) and N-heterocycles in an undivided cell at a constant current. We use a mixture of CH3CN and equivalent amounts of H2O as co-solvent at room temperature. It is crucial to produce a stoichiometric amount of active hydroxyl ions through the cathodic reduction of water. Cyclic voltammetry (CV) studies and control experiments confirm that the cycloaddition reaction is specific to the electrode electron transfer process, eliminating the need for a mediator to shuttle electrons. This metal- and oxidant-free strategy is highly compatible with different functional groups and produces products with moderate to good yields. We have successfully tetrazolated bioactive compounds at a late stage, scaled up batches efficiently, and synthesized free amino-containing N-heterocycles via denitrogenation of tetrazoles.

HNTf2-Catalyzed Formal [3 + 2] Cycloaddition of Vinyldiazoacetates to Indole-Substituted Diazo Compounds and Their Conversion to Carbazoles.

Triflimide catalysis of the [3 + 2]-cycloaddition of 3-indolymethanols with vinyldiazoacetates provides general access to β-tetrahydrocyclopenta[b]indol-substituted α-diazoesters. Initiated by addition of the in situ generated vinylogous iminium electrophile from 3-indolymethanol to the vinylogous position of the vinyldiazo compound and completed by intramolecular cyclization from the vinyldiazonium ion intermediate, this transformation occurs in good yields and excellent diastereoselectivity with a broad substrate scope under mild conditions. The resulting α-diazoesters undergo Rh2(OAc)4-catalyzed substrate-dependent 1,2-migration to form multisubstituted carbazoles in high yields.

Tuning Regioselectivity in the [3 + 2] Cycloaddition of Alkynyl Sulfonium Salts with Binucleophilic N-Aryl Amidines.

A tunable reaction manifold of alkynyl sulfonium salts with binucleophilic N-aryl amidines in the absence of any transition metal catalyst is first reported. This methodology involves sequential addition/cyclization that is perfectly tuned by stepwise addition of K2CO3, affording a plethora of valuable 1,2,4- and 1,2,5-trisubstituted imidazoles in good yields with high regioselectivity. Importantly, trapping and isolation of the reactive intermediate unveiled the reaction mechanism of β-attack on the triple bond in this [3 + 2] cycloaddition reaction.

A Green one-pot three component synthesis of thiazolidine-2,4-dione based bisspirooxindolo-pyrrolidines with [Bmim]BF4: their in vitro and in silico anti-TB studies.

A simple and effective three-component one-pot green methodology was employed for the synthesis of a new thiazolidine-2,4-dione based bisspirooxindolo-pyrrolidine derivatives using [Bmim]BF4 ionic liquid via [3 + 2] cycloaddition reaction. It is an environmentally benign, column chromatography-free, shorter reaction time, good yield and easy product isolation method. The synthesized compounds 10a-x, were thoroughly characterized by using various spectroscopic methods like FT-IR, 1H NMR, 13C NMR, Mass spectrometry and finally by single crystal X-ray diffraction method. In vitro anti-tubercular (anti-TB) activity studies were carried out on these synthesized compounds, and they showed good to moderate anti-TB activity against Mycobacterium tuberculosis H37Rv strain. The compound 10a exhibited good anti-TB activity, with an MIC (Minimum Inhibitory Concentration) value of 12.5µg/mL, and the compounds 10m, 10o and 10r showed moderate activity with an MIC value of 25.0µg/mL. Remaining compounds exhibited poor activity against Mycobacterium tuberculosis. Ethambutol, rifampicin and isoniazid were used as standard drugs. Furthermore, in silico molecular docking experiments on the TB protein (PDB ID: 1DF7) were carried out to understand the binding interactions, and they showed least binding energy values ranging from -8.9 to -7.2kcal/mol.

Desulfurdioxidative N‐N Coupling of N‐Arylhydroxylamines and N‐Sulfinylanilines: Reaction Development and Mechanism

AbstractA highly efficient and chemoselective approach for the divergent assembling of unsymmetrical hydrazines through an unprecedented intermolecular desulfurdioxidative N−N coupling is developed. This metal free protocol employs readily accessible N‐arylhydroxylamines and N‐sulfinylanilines to provide highly valuable hydrazine products with good reaction yields and excellent functional group tolerance under simple conditions. Computational studies suggest that the in situ generated O‐sulfenylated arylhydroxylamine intermediate undergoes a retro‐[2π+2σ] cycloaddition via a stepwise diradical mechanism to form the N−N bond and release SO2.

Changes in the corn yield structure depending on genetic characteristics, background mineral nutrition and sowing time in the Khabarovsk Krai

This study presents the results of a three-factor experiment on corn yield structure depending on the genetic characteristics and hybrids, mineral nutrition background and sowing dates. The experiment was carried out in Khabarovsk Krai in fourfold repetition on corn crops of local selection varieties Birsu, ALitet 2 and Guran 2 and hybrids of foreign selection Moldavsky 215 SV, P 7515, P 8521, P 7460; on three mineral nutrition backgrounds: № 1 (control) – N90P90K90, № 2 – N110P110K90, № 3 – N130P130K90; in 2 sowing dates with 5 days apart. The studies were carried out in 2021–2022 on the experimental field of the Far Eastern Agricultural Research Institute, the soil of the experimental section was meadow-brown, heavy loamy. The highest grain yield up to 125.3 c/ha was noted on the mineral nutrition background № 2 (N110P110K90) and № 3 (N130P130K90). Yield structure indicators depended more on varietal features of plants (46.0–73.4%) rather than on mineral nutrition background (6.2–17.8%) and sowing dates had sufficient influence (0.18–2.59%). However, the weight of 1000 grains was more influenced by additional application of nitrogen and phosphorus (40.67%) rather than varietal features (32.71%). In this study varieties of local breeding Alitet 2 and Guran 2 are recommended for cultivation in Khabarovsk Krai as they give a good grain yield, responsive to the additional application of nitrogen and phosphorus, correspond to the region conditions in terms of precocity, suitable both for harvesting silage and green fodder and for harvesting grain forage.

Catalytic activity of TiO2 nanoparticles in cyclization reactions for pyrazolone formation: DNA binding analysis via spectroscopy, X-ray crystallography, and molecular docking

This method of sustainable synthesis utilizes a range of aromatic/heterocyclic aldehydes, phenylhydrazine, and ethyl acetoacetates. The TiO2 nanoparticle catalyst facilitates cyclization reactions, yielding pyrazolone derivatives with exceptional efficiency (95–97 %) under reflux conditions at 80 °C. The current method achieves high yields of the corresponding cyclo-products in a short reaction time. A variety of physicochemical methods were employed to ascertain the chemical characteristics and structure of the synthesized heterocycles, and the geometrical structure of the well-crystallized compound (Z)-4-((5-bromofuran-2-yl)methylene)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one was characterized by the use of single-crystal X-ray diffraction measurement. The morphology and elemental composition of TiO2 nanoparticles were examined using SEM/EDX before and after the model reaction. A drop in the Ti (titanium) signal following the reaction indicates surface alterations. The present process provides a new and improved synthesis process for the formation of pyrazolones that is more convenient, well organized in terms of good yields, a simple handling procedure, a short reaction time, and user-friendliness compared to other surviving procedures. One of the synthesized compounds, (Z)-4-((5-bromofuran-2-yl)methylene)-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one (2), exhibited significant DNA binding activity. This was further confirmed by a molecular docking study, which revealed a binding energy of −7.2 kcal/mol, and by analyzing the mode of interaction.

Metal-Free Cyanation of gem-Difluoroalkenes via Azide-Mediated C-C Double Bond Fragmentation.

Activation and cleavage of C-C double bonds are long-standing challenges in synthetic chemistry. Herein, we report an unprecedented azide-mediated C-C double bond fragmentation of gem-difluoroalkenes under mild and metal-free conditions, enabling the efficient synthesis of structurally diverse aromatic nitriles in moderate to good yields. This protocol is also amenable to the cyanation of gem-dichloro and dibromo alkenes. This reaction features simple operation and good functional group compatibility and can be implemented at a gram scale.

Screening of Elite Groundnut (Arachis hypogea L.) Cultures Suitable for High Rainfall Areas of Andhra Pradesh

Groundnut is an important self-pollinated oil seed crop grown in Andhra Pradesh. It is one of the major oil seed crops used for both edible oil and table purpose. Groundnut crop requires a rainfall of 400-500 mm. In North coastal zone of Andhra Pradesh, the annual rainfall ranges from 1100-1200 mm, which favours vegetative growth in groundnut grown in kharif season resulting in low yields. The main objective of the present study is to identify suitable varieties with high pod yield in high rainfall areas suitable to North Coastal Zone of Andhra Pradesh. Twelve elite groundnut cultures along with four checks are tested during Kharif 2022 at Agricultural Research Station, Yellamanchili. The results revealed that among all the entries, K1909 recorded significant pod yield of 2740 kg/ha followed by K 2313 with 2673 kg/ha when compared with the checks K 1812 (2488 kg/ha), Dharani (1679 kg/ha), K-6 (1429 kg/ha) and Dheeraj (1307 kg/ha). These two groundnut cultures K1909 and K 2313 may be recommended to farmers of North coastal Zone of Andhra Pradesh for achieving good yields in Groundnut.

Visible-Light-Induced Regioselective Radical-Polar Crossover 1,4-Hydrophosphinylation of 1,3-Enynes: Access to Trisubstituted Allenes Bearing a Phosphine Oxide Group.

The radical 1,4-functionalizations of 1,3-enynes have emerged as a powerful strategy for the synthesis of multisubstituted allenes. However, the phosphorus-centered radical-initiated transformations remain largely elusive. Herein, visible-light photoredox catalytic regioselective radical hydrophosphinylation of 1,3-enynes with diaryl phosphine oxides as phosphinoyl radical precursors has been realized. This protocol features mild conditions, a wide substrate scope, and good functional group tolerance, producing a diverse range of phosphinoyl-substituted allenes in moderate to good yields with high atom economy. Detailed mechanistic experiments revealed a radical-polar crossover process in the reaction.

Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis.

Consistent introduction of novel enzymes is required for developing efficient biocatalysts for challenging biotransformations. Absorbing catalytic modes from organocatalysis may be fruitful for designing new-to-nature enzymes with novel functions. Herein we report a newly designed artificial enzyme harboring a catalytic pyrrolidine residue that catalyzes the asymmetric Michael addition of cyclic ketones to nitroolefins through enamine activation with high efficiency. Diverse chiral γ-nitro cyclic ketones with two stereocenters were efficiently prepared with excellent stereoselectivity (up to 97% e.e., >20:1 d.r.) and good yield (up to 86%). This work provides an efficient biocatalytic strategy for cyclic ketone functionalization and highlights the usefulness of artificial enzymes for extending biocatalysis to further non-natural reactions.

Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis

Consistent introduction of novel enzymes is required for developing efficient biocatalysts for challenging biotransformations. Absorbing catalytic modes from organocatalysis may be fruitful for designing new‐to‐nature enzymes with novel functions. Herein we report a newly designed artificial enzyme harboring a catalytic pyrrolidine residue that catalyzes the asymmetric Michael addition of cyclic ketones to nitroolefins through enamine activation with high efficiency. Diverse chiral γ‐nitro cyclic ketones with two stereocenters were efficiently prepared with excellent stereoselectivity (up to 97% e.e., >20:1 d.r.) and good yield (up to 86%). This work provides an efficient biocatalytic strategy for cyclic ketone functionalization and highlights the usefulness of artificial enzymes for extending biocatalysis to further non‐natural reactions.

Tandem four-component reaction to access fused polycycles exhibiting aggregation-enhanced through-space charge transfer emission.

Rapid construction of new fluorescence emitters is essential in advancing synthetic luminescent materials. This study illustrated a piperidine-promoted reaction of chiral dialdehyde with benzoylacetonitrile and malonitrile, leading to the formation of the 6/6/7 fused cyclic product in good yield. The proposed reaction mechanism involves a dual condensation/cyclization process, achieving the formation of up to six bonds for fused polycycles. The single crystal structure analysis revealed that the fused cyclic skeleton contains face-to-face naphthyl and cyanoalkenyl motifs, which act as the electronic donor and acceptor, respectively, potentially resulting in through-space charge transfer (TSCT) emission. While the TSCT emissions were weak in solution, a notable increase in luminescence intensity was observed upon aggregation, indicating bright fluorescent light. A series of theoretical analyses further supported the possibility of spatial electronic communication based on frontier molecular orbitals, the distance of charge transfer, and reduced density gradient analysis. This work not only provides guidance for the one-step synthesis of complex polycycles, but also offers valuable insights into the design of aggregation-enhanced TSCT emission materials.

Methyl 6-Benzyl-3-Hydroxy-3,6-Dimethyl-1,2-Dioxane-4-Carboxylate

Plasmodium falciparum is a fast-evolving parasite responsible for the fatal disease malaria, making it crucial to renew our therapeutic arsenal. Modulating the artemisinin’s endoperoxide pharmacophore is a promising route to synthesizing new antimalarial derivatives. For the first step of our 20 mmol scale synthesis, catalyzed by manganese (III) acetylacetonate, we applied the conditions previously described in the literature to one of our low-yielding asymmetrically disubstituted alkenes, (2-methylallyl)benzene. Under conditions designed for alkyl derivatives, manganese (II) and (III) acetate catalyzed its peroxycyclization with methyl 3-oxobutanoate to a 1,2-dioxane ring in the presence of oxygen from air at room temperature with a 36% yield, while an oxygen atmosphere, as described in the literature, decreased the yield to 7%. Finally, under conditions designed for aryl derivatives, the yield was reduced to 30%, showing that methylallyl derivatives have an intermediate reactivity that needs further optimization to produce 1,2-dioxane ring by manganese catalyzation in good yields. This work characterizes the product obtained and discusses the most suitable reaction conditions.

One‐Step and Mild Synthesis of 3‐(1,3,4‐Oxadiazol‐2‐Yl)isoindolin‐1‐Ones Through Ugi Four‐Component Domino Dicyclization

AbstractA novel and efficient Ugi four‐component domino dicyclization strategy has been developed for one‐step constructing diverse 3‐(1,3,4‐oxadiazol‐2‐yl)isoindolin‐1‐ones with good yields, without the need for additional additives. This domino dicyclization process underwent three consecutive reactions including Ugi, aza‐Wittig and N‐acylation by utilizing (N‐isocyanimine)triphenylphosphorane, methyl 2‐formylbenzoate, primary amines, and carboxylic acids. The initial biological activity testing revealed that compound 5 i exhibited good antifungal activity against certain fungi and demonstrated versatile applications in the fields of pesticide chemistry.

Recent Advances in Mesothelioma

Abstract Purpose of Review Pleural mesothelioma (PM) is a rare but fatal cancer of the pleural surface. Most patients have a poor prognosis, despite treatment advances which have improved outcomes. Recent research has focused on improving diagnosis, prognostication and monitoring through radiological, histological and molecular techniques. This review will cover its clinical implications and highlight areas where practice is changing. Recent Findings Changes in tumour classification and histological reporting have formalised the differentiation between benign, pre-malignant and malignant pleural disease. CT and thoracic ultrasound (TUS) have good diagnostic yields for pleural biopsy, but PET-CT does not increase diagnostic yield for repeat sampling. immunohistochemistry (IHC) staining for BAP1 and MTAP/CDKN2A pathological samples can increase diagnosis rates, while serum mesothelin shows promise for disease monitoring. Phase 3 RCT results mean dual immunotherapy is the new standard of care, whereas there is no role for extended pleurectomy decortication surgery for PM. Summary Best practice for PM diagnosis and management is changing at pace. Key areas for future research involve improving PM diagnostics, therapeutics and targeted therapies. An awareness of active research and clinical trials is essential for clinicians to seek for the best outcomes for their patients.