Catalyst-free photoarylation of 2-aryl-2H-indazoles by carbon-iodine bond activation.

A photocatalyst-free visible-light induced arylation of 2-aryl-2H-indazoles with aryl iodides has been developed for the first time to produce 3,2-diaryl-2H-indazoles in good to moderate yields. In this transformation, potassium tert-butoxide acts as an activator of the C-I bond and also as a scavenger of in situ generated HI in the reaction. This method exhibits high functional group tolerance with a wide substrate scope and it has been successfully applied to the synthesis of liver X receptor agonists and also for fluorescent probes. This is the first report on the photoarylation of 2-arylindazoles at the C3-position with aryl iodides under catalyst-free conditions.

Recent advances in metal directed C-H amidation/amination using sulfonyl azides and phosphoryl azides.

Transition metal-catalyzed C-N bond formation reactions have gained popularity as a method for selectively transforming common C-H bonds into N-functionalized molecules. This approach is particularly useful for synthesizing aminated molecules, which require aminating reagents and amidated building blocks. Over the past two decades, significant advancements have been achieved in transition-metal-catalyzed C-H functionalization, with organic azides emerging as promising amino sources and internal oxidants. This review focuses on recent developments in utilizing sulfonyl and phosphoryl azides as building blocks for directed intra- and intermolecular C-H functionalization reactions. Specifically, it discusses methods for synthesizing sulfonamidates and phosphoramidates using sulfonyl and phosphoryl azides, respectively. The article highlights the potential of C-H functionalization reactions with organic azides for efficiently and sustainably synthesizing N-functionalized molecules, providing valuable insights into the latest advancements in this field.

Rh(III)-catalyzed [3 + 2] spiroannulation of 2,3-dihydro-1,4-benzoxazines with 4-hydroxy-2-alkynoates through ortho-C-H bond functionalization.

Rhodium(III)-catalyzed [3 + 2]-spiroannulation of 2-aryl-1,4-benzoxazines with 4-hydroxy-2-alkynoates has been developed for the synthesis of highly rigid spirolactones in good yields with high regioselectivity. The reaction proceeds through a cascade of C-H activation followed by C-H annulation and lactonization. In this approach, two C-C and C-O bonds are formed in a single step. This is the first report on the spiroannulation of 2,3-dihydro-1,4-benzoxazines with 4-hydroxy-2-alkynoates.

Rhodium(III)-catalyzed oxidative annulation of N-arylbenzamidines with maleimides via dual C-H activation.

An oxidative annulation of N-arylbenzimidamides with maleimides has been developed for the first time using a catalytic amount of the [Cp*RhCl2]2 complex for the synthesis of a diverse range of 1H-benzo[4,5]imidazo[2,1-a]pyrrolo[3,4-c]isoquinoline-1,3(2H)-dione derivatives. This method is versatile and atom-economical for producing polycyclic benzo[4,5]imidazo[2,1-a]pyrrolo[3,4-c] isoquinoline-1,3(2H)-dione scaffolds in a single step.

Nanoparticulate Silica Internalization and Its Effect on the Growth and Yield of Groundnut (Arachis hypogaea L.).

In recent years, foliar applications of nanoparticles are increasingly being employed in agricultural fields as fertilizers to enhance crop yields. However, limited studies are available on the foliar uptake of nanoscale nutrients and their interaction with plants. In this study, we reported the effects of foliar spray with varied concentrations of nanoscale silica (N-SiO2) and bulk tetraethyl orthosilicate (TEOS at 2000 ppm) on the growth and yield of groundnut. Nanosilica was prepared by a sol-gel method and characterized by transmission electron microscopy, dynamic light scattering, and X-ray diffraction. The size and zeta potential of N-SiO2 were found to be 28.7 nm and 32 mV, respectively. The plant height, number of branches, total dry weight, SPAD chlorophyll meter reading, photosynthetic rate, water use efficiency, number of nodules, and ascorbic acid content were increased significantly with the N-SiO2 foliar application at 400 ppm over control. The number of filled pods increased significantly by 38.78 and 58.60% with N-SiO2 at 400 ppm application over TEOS and control, respectively. The pod yield per plant in N-SiO2 at 400 ppm increased by 25.52 and 31.7% higher over TEOS and control, respectively. Antioxidant enzyme activities enhanced significantly in N-SiO2 at 200 and 400 ppm over control, indicating a stimulatory effect on the plant growth. In addition, confocal microscopy revealed that fluorescein isothiocyanate (FITC)-N-SiO2 entered through stomata and then transported to vascular bundles via apoplastic movement. Our study for the first time demonstrated that N-SiO2 can significantly modulate multiple complex traits in groundnut through an eco-friendly and sustainable approach.

Identification of genomic regions governing moisture and heat stress tolerance employing association mapping in rice (Oryza sativa L.).

BACKGROUND: Rice crop is damaged extremely by abiotic stress world-wide. The best approach to enhance drought tolerance in rice varieties is to identify and introgress yield QTLs with major effects. The Association mapping approach helps in the identification of genomic regions governing physiological, yield and yield attributes under moisture and heat stress conditions in diverse collections of crop germplasm, based on historic recombination events and linkage disequilibrium across the genome. METHODS AND RESULTS: The association mapping panel of 110 rice germplasm lines exhibited significant variation for all the traits in both irrigated and moisture stress conditions. The extent of yield reduction ranged to 83% during rabi, 2018-19, 53% in rabi, 2019-20 and 68% in pooled analysis. The genotypes Badami, Badshabhog, Pankaj, Varalu, Vasundhara, Vivekdhan, Krishna and Minghui63 exhibited drought tolerance with least yield penalty under moisture stress conditions. The genotypes Konark, MTU3626, NLR33671, PR118 and Triguna exhibited minimal reduction in heat stress tolerance traits. Association mapping of germplasm using 37808 SNP markers detected a total of 10 major MTA (Marker-trait association) clusters distributed on chromosomes 1, 3, 4 and 11 through mixed linear model (MLM) governing multiple traits from individual data analysis which are consistent across the years and situations. The pooled data generated a total of five MTA clusters located on chromosome 6. In addition, several novel unique MTAs were also identified. Heat stress analysis generated a total of 23 MTAs distributed on chromosomes 1, 5, 6 and 11. Candidate gene analysis detected a total of 53 and 38 genes under individual and pooled data analysis for various yield and yield attributes under control and moisture stress conditions, respectively and a total of 11 candidate genes in heat stress Conditions. CONCLUSION: The major and novel MTAs identified in the present investigation for various drought and heat tolerant traits can be utilized for breeding climate-resilient rice varieties. The candidate genes predicted for key MTAs are of great value to deploy into the rice breeding after functional characterization.

Synthetic Applications of Prins Cyclization in Natural Product Syntheses.

The natural products having tetrahydropyran unit with multiple chiral centers serve as magnificent building blocks for various active pharmaceutical ingredients (APIs). 'Prins cyclization is one of the wonderful strategies to construct tetrahydropyran unit stereoselectively in asymmetric synthesis. In this account, we discuss our research efforts toward the synthesis of various natural products from the past two decades (2005-2020) by using Prins cyclization as a key step. Further, the synthetic utility of this reaction was investigated and well demonstrated on various molecules successfully.

First Report of 'Candidatus Phytoplasma aurantifolia' Related Strain (16SrII-D) Associated with Stunting, Little Leaf and Phyllody Disease of Pearl Millet from South India.

Pearl millet [Pennisetum glaucum (L).R.Br.] also known as bajra, is one of the oldest millets and is cultivated in dry regions of arid and semi-arid tropics where no other cereal can be successfully grown. Pearl millet cultivation in India accounts for about two-thirds of millet production and is the fourth most cultivated food crop after rice, wheat and maize in India (Reddy et al. 2021a). In February 2021, the typical symptoms of stunting, phyllody and little leaf were observed after 25-30 days after sowing pearl millet seeds at Agricultural Research Station in Perumallapalle, Tirupati, India (Fig.1 A-C). The disease incidence was recorded up to 20% in the sampling regions. Total DNA was extracted from two symptomatic and two asymptomatic plant samples using CTAB DNA extraction method (Murray and Thompson, 1980). The extracted DNA was amplified in direct PCR and nested PCR assay using phytoplasma 16S rRNA universal primer pairs P1/P7 and R16F2n/R16R2 (Gundersen and Lee.1996) and secA gene with secAfor1/SecArev3 and SecAfor2/SecArev3 primer pairs (Hodgetts et al. 2008). 16SrRNA (1.25 kb) and secA (600 bp) gene amplicons were obtained from two symptomatic samples by nested PCR. No amplicons were produced with DNA from healthy leaf samples. Nested PCR amplified products (1.25 kb and 600 bp) from the symptomatic samples corresponding to the F2nR2 region of 16S rRNA and secA were directly sequenced at automated DNA sequencing facility (Eurofin Genomics India Pvt., Ltd Bangalore) and sequence data was deposited to NCBI GenBank with accession number ON005559 and ON067810. BLAST analysis revealed that pearl millet phytoplasma strain shared 100% sequence identity in 16Sr RNA and secA genes to 'Canditatus Phytoplasma aurantifolia' related strains (Acc. Nos. OM616883 and MT952965) from India. The subgroup was identified as 16SrII-D using the iPhyClassifier based on the virtual RFLP pattern derived from the query 16S rDNA F2nR2 fragment (Zhao et al. 2009). The virtual RFLP pattern is similar to the reference pattern of 16SrII-D (Y10096) with similarity coefficient 1.00. Phylogenetic analysis of 16S rRNA and secA gene sequences using MEGA version 7.0 revealed that the pearl millet phytoplasma strain clustered with 'Ca. P. aurantifolia' isolates of 16SrII-D subgroup. (Fig.1D-E) Earlier, one of 16SrI-B-phytoplasma strain (HM 134245) associated with green ear disease of pearl millet was reported in North India (Kumar et al. 2010). In this study, we reported the association of 16SrII-D subgroup phytoplasma with little leaves and witches'-broom disease of pearl millet in South India. Phytoplasmas belonging to the 16SrII-D subgroup have a wide range of hosts, including the agricultural and horticultural crops (Reddy et al., 2021b). Hence, this is the first report of 'Ca. P aurantifolia' infection in bajra in South India. The increase in the spread of 16SrII-D sub group phytoplasma diseases and the expansion of the host range strongly suggest further studies on the epidemiology of the dynamic dissemination of this disease in India.

Enantioselective fluorination of 3-indolinone-2-carboxylates with NFSI catalyzed by chiral bisoxazolines.

A chiral Cu(i)-bisoxazoline complex catalyzed enantioselective electrophilic fluorination of 3-indolinone-2-carboxylates with NFSI has been accomplished to produce chiral 2-fluoro-3-indolinone-2-carboxylates in good yields with excellent enantioselectivities. This is the first report on the enantioselective fluorination of 2-substituted 3-indolinones using a chiral Cu(i)-bisoxazoline complex.

Synthetic approaches to FDA approved drugs for asthma and COPD from 1969 to 2020.

Respiratory infections resulting from pulmonary inflammation emerging as a leading cause of death worldwide. However, only twenty-seven new drugs were approved in the last five decades. In this review, we presented synthetic approaches for twenty-seven FDA-approved medications used to treat asthma and chronic obstructive pulmonary diseases (COPD), along with their mode of action.

Tandem Prins cyclizations for the construction of oxygen containing heterocycles.

Tandem Prins cyclization is a versatile method for the synthesis of fused/bridged/spirotetrahydropyran scaffolds. Therefore, it has become a powerful tool for the stereoselective synthesis of oxygen/nitrogen containing heterocycles. Indeed, previous review articles on Prins spirocyclization illustrate the synthesis of spirotetrahydropyran derivatives and the aza-Prins reaction demonstrates its application in the total synthesis of natural products. The current review is devoted specifically to highlight tandem Prins cyclizations for the construction of fused scaffolds and related frameworks with a particular emphasis on recent applications. The mechanistic aspects and the scope of the methods are briefly discussed herein.

Correction: Tandem Prins cyclization for the synthesis of indole fused spiro-1,4-diazocane scaffolds.

Correction for 'Tandem Prins cyclization for the synthesis of indole fused spiro-1,4-diazocane scaffolds' by Chandrashekhar Rapelli et al., Org. Biomol. Chem., 2020, 18, 6710-6715, DOI: 10.1039/D0OB01384F.

Tandem Prins cyclization for the synthesis of indole fused spiro-1,4-diazocane scaffolds.

A novel strategy has been developed for the synthesis of indole fused spiro-1,4-diazocane derivatives. Using a tandem Prins cyclization, this is the first report on the synthesis of eight-membered spirodiazocane scaffolds, which are less accessible due to ring strain but more relevant to drug discovery.

Metal-free oxidative acylation/cyclization of N-methacryloyl-2-phenylbenzoimidazole with aryl aldehydes: an easy access to benzimidazo[2,1-a]isoquinolin-6(5H)-ones.

A metal-free radical cyclization strategy has been developed for the synthesis of fused benzimidazo[2,1-a]isoquinolin-6(5H)-one derivatives from N-methacryloyl-2-arylbenzoimidazole and aryl aldehydes using 70% tert-butylhydroperoxide in water (TBHP). The reaction proceeds through a sequential acyl radical addition/cyclization strategy. This method is useful for the generation of biologically relevant tetracyclic scaffolds in a single-step process.

Synthesis and biological evaluation of 1-amino isochromans from 2-bromoethyl benzaldehyde and amines in acid medium.

We have developed a facile and efficient synthetic route to substituted isochromans for the first time by reacting 2-(2-bromoethyl)benzaldehyde with a variety of aryl, heteroaryl amines in AcOH. The reaction is catalyst/additive free and takes place at reflux conditions with short reaction time to furnish products in good to excellent yields. All the compounds have been characterized by spectral techniques such as IR, 1H NMR and Mass etc. Synthesized compounds were evaluated for antimicrobial activity against specific bacterial like 1) Staphylococcus strains aureus 2) Bacillus subtilis 3) Escherichia coli 4) Pseudomonas aeruginosa. Compounds 3e, 3n, 3 m, 3 l, 3 k, 3j and 3b showed most potent in vitro activity against bacterial strains.

Silver(i)-catalyzed sequential hydroamination and Prins type cyclization for the synthesis of fused benzo-δ-sultams.

An intramolecular annulation strategy has been developed for the synthesis of tetrahydrobenzo[e]pyrano[4,3-c][1,2]thiazine derivatives by means of coupling of aldehydes with 2-(4-hydroxybut-1-yn-1-yl)-N-arylsulfonamides using a catalytic amount of silver hexafluoroantimonate in toluene at 80 °C. This is the first report on the synthesis of fused benzo-δ-sultam derivatives through C-N, C-O, and C-C bond formations. The reaction proceeds through a cascade of hydroamination and Prins type cyclization.

1,5-Electrocyclization of conjugated azomethine ylides derived from 3-formyl chromene and N-alkyl amino acids/esters.

A novel strategy has been developed for the synthesis of chromeno[3,4-b]pyrrol-4(3H)-one and substituted pyrrole derivatives through 1,5-electrocyclization of conjugated azomethine ylides. This is the first example of the preparation of highly substituted pyrrole derivatives from chromene-3-carboxaldehydes (non-enolizable aldehydes) and N-alkyl amino acids/esters. This method is simple and applicable to a diverse range of substrates.

Novel SAHA analogues inhibit HDACs, induce apoptosis and modulate the expression of microRNAs in hepatocellular carcinoma.

In eukaryotes, transcriptional regulation occurs via chromatin remodeling, mainly through post translational modifications of histones that package DNA into structural units. Histone deacetylases (HDACs) are enzymes that play important role in various biological processes by repressing gene expression. Suberoylanilide hydroxamic acid (SAHA) is a known HDAC inhibitor that showed significant anti cancer activity by relieving gene silencing against hematologic and solid tumors. We have designed and synthesized a series of SAHA analogs C1-C4 and performed biological studies to elucidate its anti-cancer effects. It is observed that SAHA analogs significantly inhibited cell proliferation and induced apoptosis in hepatocellular carcinoma (HCC) cell lines HepG2 and SK-HEP-1. These analogs also showed non-toxic activity towards primary human hepatocytes, which describes its tumor specificity. SAHA analogs exhibited strong HDAC inhibition, which is 2-3 fold higher compared to SAHA. Moreover, these molecules induced hyper acetylation of histone H3 at various positions on the lysine residue. Further, it is observed that SAHA analogs are strong inducers of apoptosis, as they regulated the expression of various proteins involved in both extrinsic and intrinsic pathways. Interestingly, SAHA analogs induced upregulation of tumor suppressor miRNAs by activating its biogenesis pathway. Further, it is confirmed by microRNA (miRNA) prediction tools that these miRNAs are capable of targeting various anti-apoptotic genes. Based on these findings we conclude that SAHA analogs could be strong HDAC inhibitors with promising apoptosis inducing nature in HCC.

Sequential aza-Piancatelli rearrangement/Friedel-Crafts alkylation for the synthesis of pyrrolo[1,2-d]benzodiazepine derivatives.

2-Furylcarbinols undergo a smooth aza-Piancatelli rearrangement followed by Friedel-Crafts alkylation with a bifunctional substrate, (1H-pyrrol-1-yl)aniline, in the presence of 10 mol% In(OTf)3 in acetonitrile at room temperature to afford the corresponding hexahydrobenzo[b]cyclopenta[f]pyrrolo[1,2-d][1,4]diazepin-11(4aH)-one scaffolds in good yields. This method offers significant advantages such as high conversions, mild reaction conditions, short reaction times, and high selectivity. The relative stereochemistry of the product was established by nOe studies.

An efficient lactamisation/N-acyliminium Pictet-Spengler domino strategy for the diasteroselective synthesis of polyhydroxylated quinoxalinone, ß-carboline and quinazolinone derivatives.

A novel cascade strategy has been developed for the synthesis of polyhydroxylated tetrahydroindolo[1,2-a]pyrrolo[2,1-c]quinoxaline, tetrahydrodipyrrolo[1,2-a:2',1'-c]quinoxaline, hexahydro-1H-indolizino[8,7-b]indole, hexahydrobenzo[6,7]pyrrolo[1',2':1,2]azepino[3,4-b]indole, tetrahydrobenzo[4,5]imidazo[1,2-c]pyrrolo[1,2-a]quinazoline, and tetrahydropyrrolo[1,2-a]tetrazolo[1,5-c]quinazoline scaffolds. The key step is a lactamisation/Pictet-Spengler condensation of a bifunctional sugar-derived hydroxy-γ-lactone component with an appropriate bifunctional aromatic amine component. This modular approach features the in situ-generation of a cyclic N-acyliminium intermediate that allows the diastereoselective assembly of these diverse polycyclic systems efficiently under mild and operationally simple conditions.