Broad Groups Research Articles

Copper‐Catalyzed Regioselective Cyanation/Diarylmethylation of Formamides: Construction of α‐Cyano Functionalized Tetra‐Substituted Olefins

Comprehensive SummaryA copper‐catalyzed cyanation/diarylmethylation of formamides has been developed for the synthesis of α‐cyano functionalized tetra‐substituted olefins by utilizing para‐quinone methides (p‐QMs) and trimethylcyanosilane as functionalization sources. Various kinds of p‐QMs and formamides are well tolerated, delivering the desired products with 72%—94% yields, demonstrating broad functional group tolerance. Notably, the reaction does not require noble metals and proceeds regioselectively under mild conditions. Based on step‐by‐step control experiments, Hammett studies and DFT calculation, a plausible mechanism is proposed.

Organic Photoredox Catalytic Difluoroalkylation of Unactivated Olefins to Access Difluoro-Containing Tetrahydropyridazines.

Herein, we disclose a readily available phenothiazine derivative as an organocatalyst, which upon excitation with 371 nm light acquires a strongly reducing power and serves to induce the radical cascade difluoromethylation/cyclization reaction of N-homoallylacetohydrazides. A variety of CF2COR-tetrahydropyridazines have been obtained in moderate to excellent yields. This catalytic platform proceeds under metal-free conditions with a wide substrate scope and broad functional group compatibility, which unlocks the new reactivity of phenothiazine derivatives and adds significant synthetic value to N-heterocycles.

Friedel–Crafts Reactivity with Sulfondiimidoyl Fluorides for the Synthesis of Heteroaryl Sulfondiimines

AbstractSulfur functional groups are ubiquitous in molecules used in the pharmaceutical and agrochemical industries, and within these collections sulfones hold a prominent position. The double aza‐analogues of sulfones, sulfondiimines, offer significant potential in discovery chemistry but to date their applications have been limited by the lack of convenient synthetic routes. The existing methods mainly rely on imination of low‐valent‐sulfur intermediates, or the combination of pre‐formed organometallic reagents and electrophilic S(VI)‐functionalities. Herein, we describe a Friedel–Crafts‐type reaction of sulfondiimidoyl fluorides with (hetero)aryls. This new SuFEx reactivity benefits from broad functional group tolerance, mild reaction conditions, and does not require the use of pre‐formed organometallic reagents. The efficient use of unprotected indoles and pyrroles, as well as furan, thiophene and carbocyclic aromatics, further demonstrates the advantages of these reactions. We show that the reactivity of the sulfondiimidoyl fluorides can be tuned by switching the N‐substituents, allowing an expansion of the range of coupling partners. The utility of the transformation is exemplified by the synthesis of the sulfondiimine analogue of the HIV‐I reverse transcriptase‐inhibitor L‐737,126.

Synthesis of CF3CH2‐Amides/Propiolamides/Acrylamides: The TfOH Catalyzed Reactions of Nitrile Compounds with CF3CHN2

AbstractAn efficient and operationally simple protocol to access N‐(2,2,2‐trifluoroethyl)amides/propiolamides and acrylamides via direct conversion of easily accessible nitriles (aryl/alkyl/alkynyl/vinyl) and in situ generated CF3CHN2 as trifluoroethylating reagent has been developed. The protocol offers broad functional group tolerance under mild reaction conditions. Furthermore, the conversion of trifluoroethylated propiolamide into its triazole analog via Ru‐catalyzed [3+2] cycloadditions using BnN3 clearly indicates its versatility in the synthetic applications.

Glycosylium Ions in Superacid Mimic the Transition State of Enzyme Reactions.

The hydrolysis of glycosides is a biochemical transformation that occurs in all living organisms, catalyzed by a broad group of enzymes, including glycoside hydrolases. These enzymes cleave the glycosidic bond via a transition state with substantial oxocarbenium ion character, resulting in short-lived oxocarbenium ion-like species. While such transient species have been inferred through theoretical studies and kinetic isotope effect measurements, their direct spectroscopic characterization remains challenging. In this study, we exploit a superacid environment to generate, accumulate, and fully characterize nonprotected 2-deoxy glycosyl cations in the d-glucopyranose, d-galactopyranose, and l-arabinofuranose series using low-temperature NMR spectroscopy, supported by DFT calculations. Additionally, QM/MM MD simulations reveal that the properties of these glycosyl cations in superacid closely resemble those within the active sites of glycosidase enzymes, particularly in terms of conformation and anomeric charge distribution. These findings highlight a parallel between the stabilizing effect of counterions in superacid media and the network of multidentate noncovalent interactions within glycosidase active sites, which stabilize transition states with pronounced oxocarbenium ion character.

Cobalt-Hydride-Catalyzed Alkene-Carboxylate Transposition (ACT) of Allyl Carboxylates.

The alkene-carboxylate transposition (ACT) of allyl carboxylates is one of the most atom-economic and synthetically reliable transformations in organic chemistry, as allyl carboxylates are versatile synthetic intermediates. Classic ACT transformations, including [3,3]-sigmatropic rearrangement and transition metal-catalyzed allylic rearrangement, typically yield 1,2-alkene/1,3-acyloxy shifted products through a two-electron process. However, position-altered ACT to produce distinct 1,3-alkene/1,2-acyloxy shifted products remains elusive. Here, we report the first cobalt-hydride-catalyzed ACT of allyl carboxylates, enabling access to these unprecedented 1,3-alkene/1,2-acyloxy shifted products via a 1,2-radical migration (RaM) strategy. This transformation demonstrates broad functional group tolerance, is suitable for late-stage modification of complex molecules, and is amenable to gram-scale synthesis. It also expands the reaction profiles of both allyl carboxylates and cobalt catalysis. Preliminary experimental and computational studies suggest a mechanism involving metal-hydride hydrogen atom transfer (MHAT) and the 1,2-RaM process. This reaction is expected to serve as the basis for the development of versatile Co-H-catalyzed transformations of allyl carboxylates, generating a wide array of valuable building blocks for synthetic, medicinal, and materials chemistry.

Secondary and Multi-micronutrient (S, B & Zn) Doses on Yield and Residual Effect on Rice-groundnut Cropping System in Alfisols of Odisha, India

Orissa is the fourth largest state in India covering an area of 15.57 m ha out of which the net sown area is 6.13 m ha. Out of 8 broad soil groups found in the state, red and laterite groups of soil occupy more than 75% of total cultivable area. Low productivity of crops in red and laterite soils are associated with deficiency of Ca, Mg, S, B and Mo (Mitra and Sahu, 1988). The DTPA extractable Zn also indicates that red and laterite soils of Orissa is deficient in available Zn and respondent to Zn application to rice crop (Anonymous, 2002; Mandal et al., 2009). Next to Zn, the deficiency of B is wide spread in many districts of the state as well as contrary (Sharma et al., 2006). Rice-Groundnut is the most prevailing cropping pattern in red and Lateritic soils of Orissa. In spite of recommended dose of NPK fertilizer, the farmers get low yield. A field experiments were carried out with rice-groundnut cropping systems in two successive cropping seasons each, to study the effect of S, B and Zn on grain yield, nutrient uptake and their accumulation. The experimental design included ten treatments, T1: control, T2 : S 40 kg/ha, T3 : B 1 kg/ha, T4 : Zn 5 kg/ha, T5 : FYM 5 t/ha, T6 : S+B, T7 : S+Zn, T8 : B+Zn, T9 : S+B+Zn and T10 : S+B+Zn+FYM replicated thrice in randomized block design. Integrated use of S + B + Zn with FYM was the ideal combination for rice-groundnut cropping system as it was more sustainable, recorded the highest yield and SYI value along with higher accumulation and uptake of nutrients. The results revealed that red and lateritic soils are poor in S and B need integrated use of S, B and Zn along with recommended dose of NPK for getting synergistic and best effect in rice-groundnut cropping system.

In situ generated CF3CHN2 with 3-ylideneoxindoles to access CF3-containing pyrazolo[1,5-c]quinazolines derivatives.

Toward a selective and facile method for the synthesis of CF3-containing pyrazolo[1,5-c]quinazolines, we developed a [3 + 2] cycloaddition/1,3-H shift/rearrangement/dehydrogenation cascade involving in situ generated CF3CHN2 and 3-ylideneoxindoles with DBU as a base. The reaction is distinguished by its mild conditions, metal-free process, operational simplicity, and broad functional group tolerance, thus presenting a convenient protocol for the construction of pyrazolo[1,5-c]quinazolines that are of interest in medicinal chemistry.

Metal-Free Decarboxylative Cyanomethylation of β-Aryl/Heteroaryl Substituted α,β-Unsaturated Carboxylic Acids to γ-Ketonitriles.

A decarboxylative cyanomethylation of β-aryl/heteroaryl substituted α,β-unsaturated carboxylic acids has been accomplished via C(sp3)-H activation of alkyl nitriles to afford diverse γ-ketonitriles by making use of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and tert-butyl hydroperoxide (TBHP). The present report offers a metal-free approach and is featured with a broad substitution pattern and functional group compatibility.

An Actual Insight into the Pathogenic Pathways of Ankylosing Spondylitis

Spondyloarthritis refers to a broad group of conditions that include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis associated with Crohn’s disease or ulcerative colitis. They have been classified by the ASAS group (ASsessment in Ankylosing Spondylitis) into axial spondyloarthritis and peripheral spondyloarthritis. Common features include the absence of autoantibodies, genetic predisposition, and clinical aspects such as axial joint involvement, peripheral manifestations, and extra-articular involvement. However, the pathogenic mechanisms remain complex and incompletely elucidated, despite the fact that the specialized literature has described several pathways that act in synergy: genetic predisposition, environmental factors (infections and mechanical stress), or innate and acquired immune mechanisms. Finally, an inflammatory response is triggered by the recruitment of a large number of inflammatory cells and the release of innate cytokines in the affected areas: joints or periarticular or extraarticular tissues. The current article aims to update and systematize the knowledge accumulated so far on this topic, focusing on the mechanisms that have been involved in the onset, progression, and severity of ankylosing spondylitis.

A photocatalytic C(sp)ꟷB bond formation employing SOMOphilic alkynyl sulfones and nucleophilic boryl radicals

Alkynylboron compounds are important scaffolds with broad applicability in Organic Synthesis. In contrast to polar or metal-catalyzed processes, here we employ a radical approach for the addition of nucleophilic boryl radicals to electrophilic SOMOphiles for the construction of the C(sp)ꟷB bond. The reaction renders the corresponding alkynylated amine boranes with broad functional group compatibility. In addition, we carried out theoretical studies by means of DFT to understand the reactivity and selectivity of the addition process.

Electrochemical C−O and C−N Arylation using Alternating Polarity in flow for Compound Libraries

AbstractEtherification and amination of aryl halide scaffolds are commonly used reactions in parallel medicinal chemistry to rapidly scan structure–activity relationships with abundant building blocks. Electrochemical methods for aryl etherification and amination demonstrate broad functional group tolerance and extended nucleophile scope compared to traditional methods. Nevertheless, there is a need for robust and scale‐transferable workflows for electrochemical compound library synthesis. Herein we describe a platform for automated electrochemical synthesis of C−X arylation (X=NH, OH) in flow to access compound libraries. A comprehensive Design of Experiment (DoE) study identifies an optimal protocol which generates high yields across>30 aryl halide scaffolds, diverse amines (including electron‐deficient sulfonamides, sulfoximines, amides, and anilines) and alcohols (including serine residues within peptides). Reaction sequences are automated on commercially available equipment to generate libraries of anilines and aryl ethers. The unprecedented application of potentiostatic alternating polarity in flow is essential to avoid accumulating electrode passivation. Moreover, it enables reactions to be performed in air, without supporting electrolyte and with high reproducibility over consecutive runs. Our method represents a powerful means to rapidly generate nucleophile independent C−X arylation compound libraries using flow electrochemistry.

Electrochemical Synthesis of Alkenylsulfonates from Alkynes, NaHSO3 and Alcohols

Comprehensive SummaryAlkenylsulfonates are commonly encountered in medicinal chemistry, polymer chemistry, and organic synthesis. In this research, an electrochemical reaction involving alkynes, NaHSO3, and alcohols has been developed. This method yields functionalized alkenylsulfonates in good yields with broad functional group tolerance. Mechanism studies indicate that anodic oxidation of inorganic sulfite, radical insertion process, and HAT process are involved in this transformation.

Assessment of genetic diversity and heterotic alignment of CIMMYT and IITA maize inbred lines adapted to sub‐Saharan Africa

AbstractDespite the breeding efforts by many institutions, maize (Zea mays L.) productivity in sub‐Saharan Africa is still low. A limited number of productive maize hybrids have been developed partly due to a lack of knowledge on the diversity and heterotic relationship of the germplasm, especially in public breeding programs. Understanding the extent of diversity, structure, and heterotic grouping of available maize germplasm originating from different breeding programs is important to enhance long‐term genetic gain in hybrid maize breeding programs by optimizing heterotic pools using modern breeding tools. Information about the genetic structure of the available germplasm could help breeders design effective breeding strategies to improve yield. This study was conducted to determine the genetic diversity, population structure, and heterotic alignment among 187 elite maize inbred lines from the IITA (International Institute of Tropical Agriculture) and CIMMYT (International Maize and Wheat Improvement Center) maize breeding programs. The inbred lines were genotyped with 9857 Diversity Array Technology sequencing based single nucleotide polymorphism markers. Hierarchical clustering revealed three major groups, with some subgroups consistent with the selection history, and pedigree of the inbred lines. Three broad groups were detected: two consisting of CIMMYT lines and a mixed group consisting of both CIMMYT and IITA inbred lines. The STRUCTURE analysis revealed six subpopulations (fixation index value = 0.58), which depicts a moderate genetic diversity among the materials. Population 2 comprises the highest number of genotypes (102) from both programs. More than 89% of the elite lines had homozygosity exceeding 95%, with the remaining lines requiring further inbreeding through repeated self‐pollination. There was inconsistency in the predetermined heterotic groups' alignment between CIMMYT and IITA elite inbred lines. Analysis of molecular variance revealed that 96% of the total variation was accounted for by differences within groups, with the remaining 4% representing the variation between groups. This suggests that the two programs can benefit from germplasm exchange for the improvement of maize productivity.

Identification of a novel mycovirus belonging to the “flexivirus”-related family with icosahedral virion

Abstract The order Tymovirales currently comprises five viral families with positive-sense RNA ((+)RNA) genomes that infect plants, fungi, and insects. Virion morphologies within the order Tymovirales differ between families, with icosahedral virions in the Tymoviridae and filamentous virions in the other “flexi”viridae families. Despite their different morphologies, these viruses are placed in the same order based on phylogenetic analyses of replicase-associated polyproteins. However, one of the families in the Tymovirales, Deltaflexiviridae, is considered to be capsidless because there have been no published reports of virion isolation. Here we report that a new “flexivirus”-related (+)RNA virus, prospectively named Fusarium oxysporum icosahedral virus 1 (FoIV1), is icosahedral, and that most deltaflexiviruses may have icosahedral virions. Phylogenetic analyses based on replicase-associated polyproteins indicated that FoIV1 forms a distinct group in the Tymovirales with some viruses originally assigned to the Deltaflexiviridae. Electron microscopy, protein analysis, and protein structure predictions indicate that FoIV1 ORF4 encodes a single jelly-roll (SJR)-like coat protein (CP) that constitutes the icosahedral virions. Results of clustering analyses based on amino acid sequences and predicted CP structures suggested that most of the deltaflexiviruses have icosahedral virions composed of SJR-like CPs as in FoIV1, rather than having filamentous virions or capsidless. These results challenge the conventional understanding of viruses in the order Tymovirales, with important implications for revising its taxonomic framework and providing insights into the evolutionary relationships within this diverse and broad host range group of (+)RNA viruses.

From Sustainable Agriculture to Sustainable Agrifood Systems: A Comparative Review of Alternative Models

This paper reviews, compares, and critically evaluates two broad groups of sustainable agriculture models: “sustainable agriculture” and “sustainable agrifood systems”. The “sustainable agriculture” models—comprising organic farming, regenerative agriculture, climate-smart agriculture, carbon-capture agriculture, and nature-based solutions—focus primarily on improving ecological sustainability through farm-level practices. These models emphasize reducing external, industrial inputs, enhancing biodiversity, and promoting climate resilience, relying on technological and market-based solutions to address environmental concerns. On the other hand, the “sustainable agrifood systems” models—agroecology, alternative food networks, and permaculture—offer more ambitious visions of systemic transformation. These approaches not only seek to implement environmentally sound practices but also aim to reconfigure the broader food system by challenging corporate power, promoting local governance, fostering food sovereignty, and prioritizing social justice. Grounded in grassroots movements, these models emphasize social justice and economic viability in addition to ecological sustainability. This paper’s contribution lies in its comparative analysis of the wide array of sustainable alternatives, highlighting both their strengths and limitations. Adopting an agrarian political economy perspective, it critiques the former camp for limited engagement with structural issues inherent in capitalist agriculture and the latter camp for underplaying the importance of industrial agriculture for national development in the Global South.

Co-Catalyzed Suzuki-Miyaura Coupling of Organoboronic Acids and Alkynyl Chlorides Using Potassium Bicarbonate as Base.

Organoboronic acids, some of the most common and widely used organoboron compounds, have not yet been used in the cobalt-catalyzed cross coupling reactions, despite cobalt demonstrating good reactivity with zinc reagents, Grignard reagents, and metal organoborates that are formed by n-butyl lithium or alkaline metal alkoxide salts and organoboron esters. Herein, a highly efficient and practical cobalt-catalyzed coupling reaction of aryl/alkenyl boronic acids and alkynyl chloride under mild reaction conditions is reported. The advantages of the organoboronic acids, along with a broad functional group compatibility and the reaction's tolerance to moisture and air, enable this reaction to be a synthetically useful protocol for the construction of a C(sp2)-C(sp) bond. Lastly, the synthesis of two natural products and a key intermediate of roxadustat was effectively accomplished using the methodology to construct the critical alkynyl-aryl bond.

Rapid Zooplankton Assessment: Evaluating a Tool for Ecosystem‐Based Fisheries Management in the Large Marine Ecosystems of Alaska

ABSTRACTEcosystem‐based fisheries management (EBFM) remains an aspirational goal for management throughout the world. One of the primary limitations of EBFM is the incorporation of basic lower trophic level information, particularly for zooplankton, despite the importance of zooplankton to fish. The generation of zooplankton abundance estimates requires significant time and expertise to generate. The rapid zooplankton assessment (RZA) is introduced as a tool whereby nontaxonomic experts may produce rapid zooplankton counts shipboard that can be applied to management in near real time. Zooplankton are rapidly counted shipboard and placed into three broad groups of zooplankton relevant to higher trophic levels: large copepods (> 2 mm), small copepods (< 2 mm), and euphausiids. A Bayesian, hierarchical linear regression modeling approach was used to validate the relationship between RZA abundances and laboratory‐processed abundances to ensure the rapid method is a reliable indicator. Additional factors likely to impact the accuracy of the RZA abundance predictions were added to the initial regression model: RZA sorter, survey, season, and large marine ecosystem (Bering Sea, Chukchi/Beaufort Sea, and Gulf of Alaska). We tested models that included the random effect of sorter nested within survey, which improved fits for both large copepods (Bayes R2 = 0.80) and euphausiids (Bayes R2 = 0.84). These factors also improved the fit for small copepods when the fixed effect of season was also included (Bayes R2 = 0.65). Additional RZA data were used to predict laboratory‐processed abundances for each zooplankton category and the results were consistent with model training data: large copepods (Bayes R2 = 0.80), small copepods (Bayes R2 = 0.64), and euphausiids (Bayes R2 = 0.88). The Bayesian models were therefore able to predict laboratory‐processed abundances with an associated error when accounting for these fixed and random effects. To demonstrate the utility of zooplankton data in management, zooplankton time series from the Bering Sea shelf were shown to vary in relation to warm and cold conditions. This variability impacted commercially important fish, notably Walleye Pollock (Gadus chalcogrammus), and these time series were used by managers using a risk table approach. The RZA method provides a rapid zooplankton population estimation in near real time that can be applied to the management process quickly, thus helping to fill a gap in EBFM.

Cleavage of the Robust Silicon–Fluorine σ‐Bond Allows Silicon–Carbon Bond Formation: Synthetic Strategies Toward Ortho‐Silyl Aryl Phosphonates

AbstractA straightforward, mild, and transition‐metal‐free three‐component coupling reaction involving arynes, phosphites, and silyl fluorides was developed through Si−F bond activation. Although the Si−F bond is one of the strongest bonds, Si−C bond formation via Si−F bond cleavage with the assistance of bidentate silicon and phosphonium Lewis acids has been successfully achieved. This unprecedented strategy provides a facile approach for synthesizing ortho‐silyl‐substituted aryl phosphonates. Notably, this method allows the use of not only dialkylarylsilyl fluorides and diarylalkylsilyl fluorides but also triarylsilyl fluorides as coupling partners, which is uncommon in the field of arylsilane synthesis. Furthermore, a variety of ortho‐silyl‐substituted aryl phosphonates were produced in moderate to good yields with broad functional group tolerance. Additionally, the versatility of ortho‐silyl‐substituted aryl phosphonates was demonstrated by the elaboration of the products into a range of silicon‐containing compounds.

Position statement of Polish Cardiac Society experts on cardiomyopathy.

Cardiomyopathies (CMs) are a very broad group of diseases, including genetically determined and acquired, and their classification is based on phenotypic characteristics. There is always a need to search for the etiology (often also to try to identify the genetic cause), which may determine the appropriate choice of clinical management. The geographical distribution of genetic variants varies as does the prevalence across populations, ethnic groups, regions, and countries. The most reliable data on the distribution of individual genetic variants come from developed countries. The phenotypic classification includes 5 main types of CM, i.e., dilated CM, hypertrophic, restrictive, arrhythmogenic right ventricular CM, and non-dilated left ventricular (LV) CM. Individual CMs are characterized by a variety of causes and different phenotypic pictures, which affect their presentation, diagnosis, and response to treatment. Within each type of CM, there are both familial and sporadic (acquired) forms. The complex presentation of CM, as well as the limited availability of screening and diagnostic tests, causes CMs to be diagnosed late, often at an advanced stage of the disease. Therapeutic management of CM is strictly determined by its type and clinical picture. Diagnostics include the assessment of symptoms, the results of imaging and genetic tests, as well as morphological, functional, and often histological assessment. This allows for personalized and dedicated clinical management. To optimize thediagnosis, treatment, and care of patients with CMs, an individualized, expert, systemic, coordinated, and often multidisciplinary structure of care is necessary. Hence, it is important to create multidisciplinary teams for CM management. We present examples of existing systemic solutions for the care of CM patients in Europe (France and Spain). Not all of these options are available to patients in our country. This article presents issues related to CM and may be the basis for developing a diagnostic and therapeutic model allowing for earlier detection of CM in Polish patients and their effective treatment.