Chromium-Catalyzed Cross-Coupling of Methyl Ketones with Cyclic Ketones toward the Selective Synthesis of ß-Branched ß,γ-Unsaturated Ketones.

Chromium-catalyzed cross-coupling of methyl ketones with cyclic ketones to ß-branched ß,γ-unsaturated ketones are reported. Interestingly, single-crossed aldol condensation products are formed, even in reactions in which a mixture of products is possible. The reaction is highly chemoselective and regioselective. This catalytic route gives a unique opportunity to integrate the chemistry of the synthetic challenge cross-coupling reaction of ketones and the alkene migration reaction into a reaction pot.

Indolyl-4H-Chromene Derivatives as Antibacterial Agents: Synthesis, in Vitro and in Silico Studies.

In this study, indolyl-4H-chromene derivatives are designed and synthesised using an eco-friendly multicomponent one-pot synthesis using benzaldehydes, nitroketene N, S-acetals, and indoles combine with InCl3 , a Lewis acid catalyst, and ethanol, an environmentally acceptable solvent. Due to antibiotic resistance, assessed these Indolyl-4H-chromene derivatives for their in vitro antibacterial activity against Gram-positive and Gram-negative bacteria, including Streptococcus pyogenes, Staphylococcus aureus, Clostridium pyrogenes, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa, using the agar well diffusion method and Minimum Inhibition Concentration (MIC) assay. Three compounds, 4-(1H-indol-3-yl)-6-methoxy-N-methyl-3-nitro-4H-chromen-2-amine, 4-(1H-indol-3-yl)-3-nitro-N-phenyl-4H-chromen-2-amine and 4-(6-Fluoro-1H-Indol-3-yl)-N-methyl-3-nitro-4H-chromen-2-amine showed better zone of inhibition (mm) and Minimum Inhibition Concentration (MIC) values of 10 µg/mL to 25 µg/mL against all bacterial types. The Ki values of 278.60 nM and 2.21 nM for compound 4-(1H-indol-3-yl)-3-nitro-N-phenyl-4H-chromen-2-amine showed improved interactions with DNA gyrase B and topoIV ParE's ATP binding sites in in silico studies.

Chemo- and Regioselective Catalytic Cross-Coupling Reaction of Ketones for the Synthesis of ß, γ-Disubstituted ß, γ-Unsaturated Ketones.

C-C bond forming reaction of ketone with aldehyde is well-studied for the synthesis of α, ß-unsaturated ketones, however, the reaction with two different ketones to unsaturated carbonyl compound has not yet been systematically studied. Probably due to the relatively low reactivity of ketones as electrophiles (aldol acceptors), its propensity for retro-aldol reaction. The reactions often suffer from unsatisfactory chemoselectivity (self- vs. crossed aldol products) and regioselectivity (thermodynamic vs. kinetic enolate). In this quest, we report here for the first time selective cross-coupling reaction of ketones to ß-branched ß, γ-unsaturated ketones by using ruthenium catalysis. Interestingly, single crossed aldol condensation products are formed even in reactions where a mixture of products is possible. Reaction is highly chemoselective, regioselective and produces H2 O as the only byproducts making the protocol environmentally benign. Method is compatible with a wide variety of sensitive functional group and applicable for even problematic aliphatic ketones as substrates. Notably, acetone was found as a three-carbon feedstock for the syntheses of simple ß, γ-unsaturated ketone compounds. The process can further be extended to the gram-scale reaction and late-stage functionalization of natural products. With the help of DFT calculations, several control experiments, and deuterium-labeling experiments, the mechanistic finding demonstrated that initial aldol-condensation of ketones to a ß, ß-disubstituted α, ß-unsaturated ketone, which further isomerizes to a ß, γ- unsaturated ketone via η3 -allyl ruthenium complex.

Design, synthesis, and characterization of non-hemolytic antimicrobial peptides related to human cathelicidin LL-37.

We designed and synthesised the N-terminally labeled cationic and hydrophobic peptides, i.e., FFKKSKEKIGKEFKKIVQKI (P1) and FRRSRERIGREFRRIVQRI (P2) related to the human cathelicidin LL-37 peptide. The integrity and molecular weight of the peptides were confirmed by mass spectrometry. The purity and homogeneity of peptides P1 and P2 were determined by comparing LCMS or analytical HPLC chromatograms. The circular dichroism spectroscopy reveals the conformational transitions upon interaction with membranes. Predictably, peptides P1 and P2 showed a random coil structure in the buffer and formed α-helix secondary structure in TFE and SDS micelles. This assessment was further confirmed by 2D NMR spectroscopic methods. The analytical HPLC binding assay measurements revealed that peptides P1 and P2 display preferential interactions with the anionic lipid bilayer (POPC:POPG) moderately than zwitterionic (POPC). The efficacies of the peptides were tested against Gram-positive and Gram-negative bacteria. It is imperative to note here that the arginine-rich P2 exerted higher activity against all the test organisms as compared with that shown by the lysine-rich peptide P1. To test the toxicity of these peptides, a hemolytic assay was performed. P1 and P2 showed very little to no toxicity for a hemolytic assay, which is significant for P1 and P2 to be used as potential therapeutic agents in practical applications. Both peptides P1 and P2 were non-hemolytic and appeared to be more promising as they demonstrated wide-spectrum antimicrobial activity.

Decrypting the multi-functional biological activators and inducers of defense responses against biotic stresses in plants.

Plant diseases are still the main problem for the reduction in crop yield and a threat to global food security. Additionally, excessive usage of chemical inputs such as pesticides and fungicides to control plant diseases have created another serious problem for human and environmental health. In view of this, the application of plant growth-promoting rhizobacteria (PGPR) for controlling plant disease incidences has been identified as an eco-friendly approach for coping with the food security issue. In this review, we have identified different ways by which PGPRs are capable of reducing phytopathogenic infestations and enhancing crop yield. PGPR suppresses plant diseases, both directly and indirectly, mediated by microbial metabolites and signaling components. Microbial synthesized anti-pathogenic metabolites such as siderophores, antibiotics, lytic enzymes, hydrogen cyanide, and several others act directly on phytopathogens. The indirect mechanisms of reducing plant disease infestation are caused by the stimulation of plant immune responses known as initiation of systemic resistance (ISR) which is mediated by triggering plant immune responses elicited through pathogen-associated molecular patterns (PAMPs). The ISR triggered in the infected region of the plant leads to the development of systemic acquired resistance (SAR) throughout the plant making the plant resistant to a wide range of pathogens. A number of PGPRs including Pseudomonas and Bacillus genera have proven their ability to stimulate ISR. However, there are still some challenges in the large-scale application and acceptance of PGPR for pest and disease management. Further, we discuss the newly formulated PGPR inoculants possessing both plant growth-promoting activities and plant disease suppression ability for a holistic approach to sustaining plant health and enhancing crop productivity.

Biosynthesis and characterization of nanoparticles, its advantages, various aspects and risk assessment to maintain the sustainable agriculture: Emerging technology in modern era science.

The current review aims to gain knowledge on the biosynthesis and characterization of nanoparticles (NPs), their multifactorial role, and emerging trends of NPs utilization in modern science, particularly in sustainable agriculture, for increased yield to solve the food problem in the coming era. However, it is well known that an environment-friendly resource is in excessive demand, and green chemistry is an advanced and rising resource in exploring eco-friendly processes. Plant extracts or other resources can be utilized to synthesize different types of NPS. Hence NPs can be synthesized by organic or inorganic molecules. Inorganic molecules are hydrophilic, biocompatible, and highly steady compared to organic types. NPs occur in numerous chemical conformations ranging from amphiphilic molecules to metal oxides, from artificial polymers to bulky biomolecules. NPs structures can be examined by different approaches, i.e., Raman spectroscopy, optical spectroscopy, X-ray fluorescence, and solid-state NMR. Nano-agrochemical is a unification of nanotechnology and agro-chemicals, which has brought about the manufacture of nano-fertilizers, nano-pesticides, nano-herbicides, nano-insecticides, and nano-fungicides. NPs can also be utilized as an antimicrobial solution, but the mode of action for antibacterial NPs is poorly understood. Presently known mechanisms comprise the induction of oxidative stress, the release of metal ions, and non-oxidative stress. Multiple modes of action towards microbes would be needed in a similar bacterial cell for antibacterial resistance to develop. Finally, we visualize multidisciplinary cooperative methods will be essential to fill the information gap in nano-agrochemicals and drive toward the usage of green NPs in agriculture and plant science study.

Deciphering the Antimicrobial Potential of Taxus wallichiana Zucc: Identification and Characterization Using Bioassay-Guided Fractionation.

Taxus wallichiana Zucc. is a high valued medicinal plant and has been mainly studied for its anti-cancer properties. However, research on its other important biological activities, such as its antimicrobial potential, still needs attention. The focus of the present study is to investigate the antimicrobial activity of secondary metabolites of T. wallichiana needles against 3 different groups of microorganisms, i. e., bacteria, actinobacteria, and fungi. Bioactive compounds from T. wallichiana needles were separated through column chromatography, and, TLC-bioautography. Mobile phases were optimized using Snyder's selectivity triangle. Antimicrobial spots were fractionated and compounds were identified by gas chromatography-mass spectroscopy (GC/MS) and liquid chromatography-mass spectrometry (LC/MS). Functional groups were characterized using Fourier transform infrared spectrometry (FTIR) and nuclear magnetic resonance (NMR) was used to identify the molecular structures. GC/MS and LC/MS data analysis confirm the presence of fatty acids (arachidic acid, behenic acid, palmitic acid, and stearic acid), vitamins (nicotinamide), and alkaloids (cinchonine, timolol), aminobenzamides (procainamide), carbocyclic sugar (myoinositol), and alkane hydrocarbon (hexadecane), having antimicrobial activity in the needles of T. wallichiana. To the best of our knowledge, this is the first report on the isolation and characterization of antimicrobial compounds from the needles of Taxus wallichiana (Himalayan yew). The data obtained from the present study will be supportive to the new drug discoveries in modern medicine with various combinations of medicinal plant's active constituents that can be used for curing many diseases.

Source dependent variation in phenolics, antioxidant and antimicrobial activity of Paeonia emodi in west Himalaya, India.

Paeonia emodi is one of the ethno therapeutically important Himalayan plants used to cure various diseases. However, a systematic investigation of the effect of altitude on phytochemical, antioxidant, and antimicrobial activity has not been reported so far. The present study assessed the variation in the bioactive compounds, antioxidant and antimicrobial activity of the leaf, and rhizome of P. emodi collected from different altitudes. Phytochemicals such as phenols, flavonoids, flavanol, tannins, emodin, and paeoniflorin were found in all the sampled populations, but the quantity varied significantly across the altitude. In leaf, phenolics, flavonoids, and tannins content positively correlated with altitude (p < 0.01), but flavanol did not show any connection. Similarly, in the rhizome, positive relation with altitude (p < 0.01) was observed in phenol, flavonoids, and paeoniflorin. Antioxidant activity measured by 1, 1-diphenyl- 2 picrylhydrazyl (DPPH) and nitric oxide assays showed a positive correlation (p < 0.05) with altitude. 2, 2-azinobis (3-ethylbenzothiazoline-6-sulphonic acid), ferric reducing antioxidant power, and hydroxyl ion assays did not show any relation with altitude. Antimicrobial activity was higher in the case of rhizome for the minimum inhibitory concentration and positively correlated with phenolics, flavonoids, and flavanol (p < 0.05). The present study further revealed that the secondary metabolites in the leaf and rhizome extracts of P. emodi are an excellent source of antioxidant and antimicrobial activity, thus validating the species' therapeutic potential. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01242-z.

Reductive Alkylation of Quinolines to N-Alkyl Tetrahydroquinolines Catalyzed by Arylboronic Acid.

A boronic acid catalyzed one-pot tandem reduction of quinolines to tetrahydroquinolines followed by reductive alkylation by the aldehyde has been demonstrated. This step-economcial synthesis of N-alkyl tetrahydroquinolines has been achieved directly from readily available quinolines, aldehydes, and Hantzsch ester under mild reaction conditions. The mechanistic study demonstrates the unique behavior of organoboron catalysts as both Lewis acids and hydrogen-bond donors.

Plant Growth Promotion at Low Temperature by Phosphate-Solubilizing Pseudomonas Spp. Isolated from High-Altitude Himalayan Soil.

Scarcity of arable land, limited soil nutrient availability, and low-temperature conditions in the Himalayan regions need to be smartly managed using sustainable approaches for better crop yields. Microorganisms, able to efficiently solubilize phosphate at low temperatures, provide an opportunity to promote plant growth in an ecofriendly way. In this study, we have investigated the ability of psychrotolerant Pseudomonas spp., isolated from high altitudes of Indian Himalaya to solubilize P at low temperature. Quantitative estimation of phosphate solubilization and production of relevant enzymes at two different temperatures (15 and 25 °C) was performed for 4 out of 11 selected isolates, namely, GBPI_506 (Pseudomonas sp.), GBPI_508 (Pseudomonas palleroniana), GBPI_Hb61 (Pseudomonas proteolytica), and GBPI_CDB143 (Pseudomonas azotoformans). Among all, isolate GBPI_CDB143 showed highest efficiency to solubilize tri-calcium phosphate (110.50 ± 3.44 µg/mL) at 25 °C after 6 days while the culture supernatants of isolate GBPI_506 displayed the highest phytase activity (15.91 ± 0.35 U/mL) at 15 °C and alkaline phosphatase (3.09 ± 0.07 U/mL) at 25 °C in 6 and 9 days, respectively. Out of five different organic acids quantified, oxalic acid and malic acid were produced in maximum quantity by all four isolates. With the exception of GBPI_508, inoculation of bacteria promoted overall growth (rosette diameter, leaf area, and biomass) of Arabidopsis thaliana plants as compared to uninoculated control plants in growth chamber conditions. The plant growth promotion by each bacterial isolate was further validated by monitoring root colonization in the inoculated plants. These bacterial isolates with low-temperature phosphate solubilization potential along with phosphatases and phytase activity at low temperature could be harnessed for sustainable crop production in P-deficient agricultural soils under mountain ecosystems.

Bioprospecting plant growth promoting endophytic bacteria isolated from Himalayan yew (Taxus wallichiana Zucc.).

The present study aims to investigate the endophytic bacteria, isolated from the roots of Taxus wallichiana Zucc. and designated as GBPI_TWL and GBPI_TWr, for their plant growth promoting traits. On the basis of phenotypic and molecular characters, the bacteria are identified as species of Burkholderia and Enterobacter, respectively. Both the bacteria could grow at wide range of temperature (5-40 °C, opt=25 °C) and pH (1.5-11.0, opt = 6-7), and tolerate salt concentration up to 12 %. While both the bacterial endophytes possessed siderophore, HCN, ammonia, and salicyclic acid producing abilities, GBPI_TWL showed IAA and ACC deaminase producing abilities, in addition. The bacteria were found to be potential phosphate solubilizers at wide temperature range (5-35 °C) by utilizing tricalcium, iron, and aluminium phosphate as substrate. Further, the bacterial isolates produced phytase and phosphatase enzymes in both acidic and alkaline conditions. Positive influence of the inoculation with the bioformulations of GBPI_TWL and GBPI_TWr was demonstrated on the test crops namely rice (Oryza sativa) and soybean (Glycine max) with respect to physico-chemical and plant growth parameters in net house experiments. The study will have implications in developing bioformulations, specifically for low temperature environments, in view of environmental sustainability.

Thin layer drying behavior of Ginkgo biloba L. leaves with respect to Ginkgolide A and Bilobalide content and microbial load.

Influence of drying temperature (30-50 °C) and relative humidity (RH: 30-80%) on moisture content, energy requirement and quality of Ginkgo biloba leaves with respect to chemical markers namely Ginkgolide A (GA) and Bilobalide (BB), and microbial load of dried materials has been analyzed. Leaves were dried in climate control chamber with varying temperature and relative humidity (RH). Total time required for attaining equilibrium was higher for low temperature at all the RH levels as well as for high RH at all the temperatures. Energy requirement was found to increase at high RH and low temperature. GA and BB concentration increased during drying in comparison to that in fresh material. Microbial load analyzed for dried samples was also found within the limit as prescribed in European Pharmacopeia under the category 3B. 40 °C temperature and 50 % RH with less drying duration was observed as suitable conditions for better recovery of BB and GA content, less microbial load and less energy consumption, during drying of G. biloba leaves.

Boric acid catalyzed chemoselective reduction of quinolines.

Boric acid promoted transfer hydrogenation of substituted quinolines to synthetically versatile 1,2,3,4-tetrahydroquinolines (1,2,3,4-THQs) was described under mild reaction conditions using a Hantzsch ester as a mild organic hydrogen source. This methodology is practical and efficient, where isolated yields are excellent and reducible functional groups are well tolerated in the N-heteroarene moiety. The reaction parameters and tentative mechanistic pathways are demonstrated by various control experiments and NMR studies. The present work can also be scaled up to obtain gram quantities and the utility of the developed process is illustrated by the transformation of 1,2,3,4-THQs into a series of biologically important molecules including the antiarrhythmic drug nicainoprol.