Diverse Family Research Articles

A novel homozygous CLN6 Tyr142Cys variant in a nonconsanguineous family with Kufs disease.

Neuronal ceroid lipofuscinoses are a genetically heterogeneous group of inherited lysosomal storage disorders. Kufs disease is the predominant form of neuronal ceroid lipofuscinosis in adults, but it's rare and challenging to diagnose. The proband initially presented with cognitive deterioration and parkinsonian traits. At 35, he was admitted to hospital following a tonic-clonic seizure. Brain magnetic resonance imaging showed atrophy of the cerebral cortex and cerebellum, enlarged ventricles, and thinned corpus callosum. The proband's younger brother and sister were also affected, and the clinical phenotype within the family was consistent. Whole-exome Sequencing of the proband revealed a novel homozygous mutation in CLN6 (NM_017882: c.425A > G, p. Tyr142Cys). Co-segregation analysis revealed that two other affected individuals carried a homozygous mutation at the same locus, with both parents exhibiting heterozygous mutations of c.425A > G. Our study not only provides insights into the clinical presentation and development of the disease within the affected family but also expanded the mutational and phenotypical spectrum of the CLN6 gene.

Practice matters: how practicum experiences change student beliefs

ABSTRACT Development of professional competencies is a key outcome of undergraduate programs preparing practitioners to work with infants and toddlers. Competencies for working with young children were examined among 1300 undergraduate students at 12 universities. Students completed a series of online questionnaires indicating their knowledge, beliefs, and hypothetical practices with young children; end-of-semester scores were analyzed using linear regression. Having had a practicum course is associated with more positive dispositions for supporting the development of teacher–child relationships, building partnerships with diverse families, guiding children’s behavior, and fostering development and learning. Further, we examined development of dispositions over the course of a semester based on undergraduates’ current and past practicum experiences. Implications for programs who prepare infant and toddler practitioners are discussed.

Comprehensive analysis of the bZIP gene family in ‘Duli’ pear (Pyrus betulifolia Bunge): Insights for research on abiotic stress, especially drought, in pear

Plants are unavoidably subjected to various abiotic stresses, such as drought, salt, and cold, during their growth and development. Drought, accompanied by water shortages in North China, has become an environmental factor seriously affecting agriculture production. Basic leucine zipper (bZIP) is one of the most diverse transcription factor families in plants. It participates in the regulation of many physiological processes and plays an important role in plants’ response to abiotic stress. In this study, for the first time, 88 bZIP family members (PbbZIPs) in ‘Duli’ pear (Pyrus betulifolia Bunge) were identified using both hidden Markov model (HMM) and basic local alignment search tool (BLAST) methods. A phylogenetic tree of all the PbbZIPs members was constructed. The physicochemical properties, subcellular localisation, chromosomal location, gene structure, conserved motifs and domains, secondary and tertiary structures, and cis-acting promoter elements of the 88 family members were comprehensively analysed. The results indicated that PbbZIPs may play relevant roles in stress response in ‘Duli’. Therefore, we determined the expressions of all PbbZIPs in ‘Duli’ seedlings under drought, salt, and cold conditions, and in seedlings treated with stress-related hormones such as abscisic acid (ABA), salicylic acid (SA), methyl jasmonate (MeJA), and melatonin (MT). PbbZIPs responsive to various abiotic stresses and hormones were screened. In addition, we determined the expression patterns of 12 PbbZIP genes that strongly responded to both drought and ABA in ‘Duli’ tissue culture plants treated with different concentrations of PEG4000 at different time points. Finally, we selected three key genes (PbbZIP65, PbbZIP77 and PbbZIP81) that may play a major role in drought resistance in ‘Duli’, and preliminarily identified their function through the VIGS method, finding that PbbZIP77 could positively regulate the drought resistance of ‘Duli’ seedlings, while PbbZIP65/81 could negatively regulate the drought resistance of ‘Duli’ seedlings. This study not only broadens our knowledge about the bZIP gene family in ‘Duli’ pear, but also provides notable guidance for further functional research on PbbZIPs in abiotic stress, especially drought resistance, in the pear plant.

Healthcare chaplains' perspectives on working with culturally diverse patients and families.

Considering the ethnic, racial, and cultural diversity in the U.S., we aim to explore the experiences of healthcare chaplains as they provide culturally sensitive care to diverse patients and their families. This is a qualitative study. Individual interviews were conducted with 14 healthcare chaplains recruited from 3 U.S. chaplaincy organizations. Thematic analysis with constant comparison yielded 6 themes in the chaplains' experiences: (1) the diverse roles of chaplains; (2) their high levels of comfort in working with diverse populations, attributed to cultural sensitivity and humility training; (3) cues for trust-building; (4) common topics of diversity, equity, and inclusion discussed; (5) gaps in chaplaincy training; and (6) the importance of collaboration and negotiation with healthcare professionals to accommodate cultural needs. This research highlights the valuable role of chaplains in providing culturally sensitive care and suggests areas for improving chaplaincy training and education to better serve diverse patient populations.

Multiscale Modeling of Physical Properties of Nanoporous Frameworks: Predicting Mechanical, Thermal, and Adsorption Behavior.

ConspectusNanoporous frameworks are a large and diverse family of supramolecular materials, whose chemical building units (organic, inorganic, or both) are assembled into a 3D architecture with well-defined connectivity and topology, featuring intrinsic porosity. These materials play a key role in various industrial processes and applications, such as energy production and conversion, fluid separation, gas storage, water harvesting, and many more. The performance and suitability of nanoporous materials for each specific application are directly related to both their physical and chemical properties, and their determination is crucial for process engineering and optimization of performances. In this Account, we focus on some recent developments in the multiscale modeling of physical properties of nanoporous frameworks, highlighting the latest advances in three specific areas: mechanical properties, thermal properties, and adsorption.In the study of the mechanical behavior of nanoporous materials, the past few years have seen a rapid acceleration of research. For example, computational resources have been pooled to create a public large-scale database of elastic constants as part of the Materials Project initiative to accelerate innovation in materials research: those can serve as a basis for data-based discovery of materials with targeted properties, as well as the training of machine learning predictor models.The large-scale prediction of thermal behavior, in comparison, is not yet routinely performed at such a large scale. Tentative databases have been assembled at the DFT level on specific families of materials, such as zeolites, but prediction at larger scale currently requires the use of transferable classical force fields, whose accuracy can be limited.Finally, adsorption is naturally one of the most studied physical properties of nanoporous frameworks, as fluid separation or storage is often the primary target for these materials. We highlight the recent achievements and open challenges for adsorption prediction at a large scale, focusing in particular on the accuracy of computational models and the reliability of comparisons with experimental data available. We detail some recent methodological improvements in the prediction of adsorption-related properties: in particular, we describe the recent research efforts to go beyond the study of thermodynamic quantities (uptake, adsorption enthalpy, and thermodynamic selectivity) and predict transport properties using data-based methods and high-throughput computational schemes. Finally, we stress the importance of data-based methods of addressing all sources of uncertainty.The Account concludes with some perspectives about the latest developments and open questions in data-based approaches and the integration of computational and experimental data together in the materials discovery loop.

Unveiling Peru’s Agricultural Diversity: Navigating Historical and Future Trends in a Post-COVID-19 Context

Over a comprehensive 5-year assessment, and extrapolating it prospectively until 2025, a thorough examination was conducted of productive agrobiodiversity in nine rural agricultural districts across Peru. The present study involved in-depth interviews with 180 representative farmers of the Coast, Highlands, and Jungle natural regions. Employing the Shannon–Weiner diversity index and the Margalef species richness index, the dynamics within years and across different zones were analyzed. Utilizing quadratic trend models, we assessed the frequency of each crop, aiming for the optimal fit concerning absolute deviation from the mean, mean squared deviation, and mean absolute percentage error. These findings revealed five distinct crop types—tuberous, fruits, cereals, legumes, and roots—distributed across 25 diverse families. Looking ahead to 2025, our projections indicated positive trends in 15 families and negative trends in 9 crop families. The nuanced mathematical distinctions observed in crop management decisions varied significantly depending on the specific area and year, underscoring the importance of localized considerations in agricultural planning.

Heterogeneric Diversity and Richness of Avifauna in a Degraded Landscape of Arial Beel in Bangladesh

Bird diversity and richness reflect the habitat quality of ecosystems. The species composition, diversity, and richness of birds were studied at Shologhar Union, a degraded landscape of Arial Beel, from March 2016 to February 2017, using line transect and point count methods. A total of 75 species of birds belonging to 14 orders and 35 families were recorded; most of them were residents (83%). Non-passerine birds were predominant (40 species, 53% of total species), with 18 families and 38 genera. Only one near-threatened species (Yellow Wattled Lapwing Vanellus malabaricus) was recorded. Among resident birds, Baya weaver (Ploceus philippinus) was dominant, and the Yellow Wagtail (Motacilla flava) was predominant among migratory birds. Most species were terrestrial (51 spp., 68% of total birds), contributing only 23% of the population. The individual rarefaction revealed the highest species richness in March and the lowest in May and June. The highest population was recorded in winter (38%), and insectivore species (40%) were the highest. No significant seasonal variation occurred in the richness of birds (Kruskal-Wallis test: K = 0.05 df = 2, p = 0.971) and in different feeding guilds (Kruskal-Wallis test: K = 0.86, df = 5, p = 0.65). Ardeidae and Sturnidae represented the highest diversified families (6 species in each, RDi = 8), and Baya Weaver contributed the highest (26%) population. The presence of different species of birds suggests that this site could provide a suitable habitat for wild birds, and restoration management of this part of Arial Beel should require conserving the habitat of avifauna. Jagannath University Journal of Life and Earth Sciences, 9(1): 19-44, 2023 (June)

Longitudinal adaptive behavioral outcomes in Ogden syndrome by seizure status and therapeutic intervention.

Ogden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011 and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia, and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time. The current study involves a total of 58 distinct participants; of these, 43 caregivers were interviewed using the Vineland-3 and answered a survey regarding therapy and other questions, 10 of whom completed the Vineland-3 but did not answer the survey, and 5 participants who answered the survey but have not yet performed the Vineland-3 due to language constraints. The average age at the time of the most recent assessment was 12.4 years, with individuals ranging in age from 11 months to 40.2 years. Using Vineland-3 scores, we show decline in cognitive function over time in individuals with Ogden syndrome (n = 53). Sub-domain analysis found the decline to be present across all modalities. In addition, we describe the nature of seizures in this condition in greater detail, as well as investigate how already-available non-pharmaceutical therapies impact individuals with NAA10-related neurodevelopmental syndrome. Additional investigation between seizure and non-seizure groups showed no significant difference in adaptive behavior outcomes. A therapy investigation showed speech therapy to be the most commonly used therapy by individuals with NAA10-related neurodevelopmental syndrome, followed by occupational and physical therapy, with more severely affected individuals receiving more types of therapy than their less-severe counterparts. Early intervention analysis was only significantly effective for speech therapy, with analyses of all other therapies being non-significant. Our study portrays the decline in cognitive function over time of individuals within our cohort, independent of seizure status, and therapies being received, and highlights the urgent need for the development of effective treatments for Ogden syndrome.

Activity-based protein profiling of serine hydrolases and penicillin-binding proteins in Enterococcus faecium

Abstract Enterococcus faecium is a gut commensal bacterium that is gaining increasing relevance as an opportunistic, nosocomial pathogen. Its high level of intrinsic and acquired antimicrobial resistance is causing a lack of treatment options, particularly for infections with vancomycin-resistant strains, and prioritizes the identification and functional validation of novel druggable targets. Here, we use activity-based protein profiling (ABPP), a chemoproteomics approach using functionalized covalent inhibitors, to detect active serine hydrolases across 11 E. faecium and Enterococcus lactis strains. Serine hydrolases are a big and diverse enzyme family, that includes known drug targets such as penicillin-binding proteins (PBPs), whereas other subfamilies are underexplored. Comparative gel-based ABPP using Bocillin-FL revealed strain- and growth condition dependent variations in PBP activities. Profiling with the broadly serine hydrolase-reactive fluorescent probe fluorophosphonate-TMR showed a high similarity across E. faecium clade A1 strains, but higher variation across A2 and E. lactis strains. To identify these serine hydrolases, we used a biotinylated probe analog allowing for enrichment and identification via liquid chromatography-mass spectrometry. We identified 11 largely uncharacterized targets (α,β-hydrolases, SGNH-hydrolases, phospholipases, amidases, peptidases) that are druggable and accessible in live vancomycin-resistant E. faecium E745 and may possess vital functions that are to be characterized in future studies.

Rare dermatosis is disseminated actinic superficial porokeratosis

Porokeratoses are a very rare group of dermatoses, acquired or hereditary, of unknown etiology, characterized by a violation of keratinization. The disease is manifested by one or more atrophic spots, each of which is surrounded by a characteristic hyperkeratotic, ridge-like border called a "horny plate". There are several forms of this pathology, among which there are sporadic cases and family variants with an autosomal dominant pattern of inheritance of various penetrance. This article presents a clinical case of the occurrence of superficial disseminated actinic porokeratosis in a 59-year-old woman after prolonged exposure to the sun. The eruptions were represented by small spots, rounded, pinkish-yellow-brown in color with an atrophic center, surrounded by a raised narrow roller with a groove on the surface, have no tendency to merge, symmetrically arranged. Screening for diseases that cause immunosuppression (human immunodeficiency virus, hematological malignancies) and renal insufficiency did not reveal pathology. Histological examination showed a typical well-limited plume of parakeratotic cells (horn plate), hypogranulosis, dyskeratotic cells or vacuolated keratinocytes, which made it possible to make a final diagnosis. Considering that insolation in this case is a causally significant factor and the likelihood of malignant neoplasms against the background of dermatosis remains, it is extremely important for such patients to use sunscreens with a high degree of protection as part of complex therapy, as well as regular skin examinations.

Biosynthetic gene clusters with biotechnological applications in novel Antarctic isolates from Actinomycetota

Actinomycetota have been widely described as valuable sources for the acquisition of secondary metabolites. Most microbial metabolites are produced via metabolic pathways encoded by biosynthetic gene clusters (BGCs). Although many secondary metabolites are not essential for the survival of bacteria, they play an important role in their adaptation and interactions within microbial communities. This is how bacteria isolated from extreme environments such as Antarctica could facilitate the discovery of new BGCs with biotechnological potential. This study aimed to isolate rare Actinomycetota strains from Antarctic soil and sediment samples and identify their metabolic potential based on genome mining and exploration of biosynthetic gene clusters. To this end, the strains were sequenced using Illumina and Oxford Nanopore Technologies platforms. The assemblies were annotated and subjected to phylogenetic analysis. Finally, the BGCs present in each genome were identified using the antiSMASH tool, and the biosynthetic diversity of the Micrococcaceae family was evaluated. Taxonomic annotation revealed that seven strains were new and two were previously reported in the NCBI database. Additionally, BGCs encoding type III polyketide synthases (T3PKS), beta-lactones, siderophores, and non-ribosomal peptide synthetases (NRPS) have been identified, among others. In addition, the sequence similarity network showed a predominant type of BGCs in the family Micrococcaceae, and some genera were distinctly grouped. The BGCs identified in the isolated strains could be associated with applications such as antimicrobials, anticancer agents, and plant growth promoters, among others, positioning them as excellent candidates for future biotechnological applications and innovations.Key points• Novel Antarctic rare Actinomycetota strains were isolated from soil and sediments• Genome-based taxonomic affiliation revealed seven potentially novel species• Genome mining showed metabolic potential for novel natural products

Contributions of mothers' and fathers' shared book reading with infants at 9 months to language skills at 18 months in ethnically and socioeconomically diverse families

AbstractUsing a sample of 286 mothers and fathers from ethnically and socioeconomically diverse backgrounds, we tested the associations between the frequency and quality of parents' shared book reading (SBR) with infants aged 9 months, and language skills of infants aged 18 months, and whether infants' attention during SBR at 9 months mediated these associations. Frequency of SBR was parent‐report and quality of SBR (i.e., number of reading strategies) and infants' attention were coded from recorded SBR interactions at home. The majority of mothers and fathers reported reading to their 9‐month‐olds at least weekly, and mothers reported reading, on average, significantly more often than fathers. There was large variability in parents' SBR quality ranging from 0 to 15 strategies per minute, with labelling being the most common. Path analysis showed that mothers' SBR frequency at 9 months was significantly associated with infants' receptive and expressive language skills at 18 months, whereas, SBR quality by either parent was not significant. Infants' attention did not mediate these associations. These findings suggest that early SBR is beneficial for language development and programmes targeting early language development should encourage both mothers and fathers to read often to their infants during the first year.

Detection of a novel pathogenic variant in KCNH2 associated with long QT syndrome 2 using whole exome sequencing

BackgroundLong QT syndrome (LQTS) is a cardiac channelopathy characterized by impaired myocardial repolarization that predisposes to life-threatening arrhythmias. This study aimed to elucidate the genetic basis of LQTS in an affected Iranian family using whole exome sequencing (WES).MethodsA 37-year-old woman with a personal and family history of sudden cardiac arrest and LQTS was referred for genetic study after losing her teenage daughter due to sudden cardiac death (SCD). WES was performed and variants were filtered and prioritized based on quality, allele frequency, pathogenicity predictions, and conservation scores. Sanger sequencing confirmed segregation in the family.ResultsWES identified a novel heterozygous frameshift variant (NM_000238.4:c.3257_3258insG; pGly1087Trpfs*32) in the KCNH2 encoding the α-subunit of the rapid delayed rectifier potassium channel responsible for cardiac repolarization. This variant, predicted to cause a truncated protein, is located in the C-terminal region of the channel and was classified as likely pathogenic based on ACMG guidelines. The variant was absent in population databases and unaffected family members.ConclusionThis study reports a novel KCNH2 frameshift variant in an Iranian family with LQTS, expanding the spectrum of disease-causing variants in this gene. Our findings highlight the importance of the C-terminal region in KCNH2 for proper channel function and the utility of WES in identifying rare variants in genetically heterogeneous disorders like LQTS. Functional characterization of this variant is warranted to fully elucidate its pathogenic mechanisms and inform personalized management strategies.

“All employees are equal … but some are more equal than others”. Role identity and nonfamily member discrimination in family SMEs

PurposeThis paper aims to investigate if, under which conditions, and with which consequences, nonfamily members have the perception of being discriminated against as a consequence of nepotism and adverse selection practices. This research also aims to investigate whether the carried-out role influences the perception of being discriminated against among nonfamily member employees.Design/methodology/approachA quantitative approach was carried out by adopting a structural equation model (SEM) analysis. The survey investigated a sample of Italian family SMEs (participating companies N = 186, total questionnaires collected N = 838).FindingsDrawing on the multiple identities theory, findings show that role salience (RS) effectively contributes to reducing the unwanted effects of perceived discrimination (PD) among nonfamily member employees. In doing so, this study deepens the knowledge of nonfamily member employment conditions and their consequences on strategic outcomes such as organizational commitment (OC), organizational justice (OJ) and intention to quit (ITQ).Research limitations/implicationsBy adopting a self-categorization approach, this study also advances current theoretical literature, as this methodological lens could help scholars further understand diversity in family business.Practical implicationsThis study suggests it would be advisable to implement human resource management practices based on job rotation to promote cohesion and reduce perceived distances.Social implicationsSMEs are the most widespread type of firm in the world; as a consequence, avoiding PD among nonfamily member employees has general ethical relevance.Originality/valueThis study expands current literature by showing that RS plays an important role in determining levels of PD. This study also advances current literature by focusing on the impact of multiple identities on fairness and commitment at individual and group levels of analysis of family businesses.

Identification of Novel Regulators of Leaf Senescence Using a Deep Learning Model.

Deep learning has emerged as a powerful tool for investigating intricate biological processes in plants by harnessing the potential of large-scale data. Gene regulation is a complex process that transcription factors (TFs), cooperating with their target genes, participate in through various aspects of biological processes. Despite its significance, the study of gene regulation has primarily focused on a limited number of notable instances, leaving numerous aspects and interactions yet to be explored comprehensively. Here, we developed DEGRN (Deep learning on Expression for Gene Regulatory Network), an innovative deep learning model designed to decipher gene interactions by leveraging high-dimensional expression data obtained from bulk RNA-Seq and scRNA-Seq data in the model plant Arabidopsis. DEGRN exhibited a compared level of predictive power when applied to various datasets. Through the utilization of DEGRN, we successfully identified an extensive set of 3,053,363 high-quality interactions, encompassing 1430 TFs and 13,739 non-TF genes. Notably, DEGRN's predictive capabilities allowed us to uncover novel regulators involved in a range of complex biological processes, including development, metabolism, and stress responses. Using leaf senescence as an example, we revealed a complex network underpinning this process composed of diverse TF families, including bHLH, ERF, and MYB. We also identified a novel TF, named MAF5, whose expression showed a strong linear regression relation during the progression of senescence. The mutant maf5 showed early leaf decay compared to the wild type, indicating a potential role in the regulation of leaf senescence. This hypothesis was further supported by the expression patterns observed across four stages of leaf development, as well as transcriptomics analysis. Overall, the comprehensive coverage provided by DEGRN expands our understanding of gene regulatory networks and paves the way for further investigations into their functional implications.

First report of the complete mitogenome of Hylemya nigrimana (Meigen, 1826) from Oriental China (Diptera: Anthomyiidae)

ABSTRACT The Anthomyiidae is a large and diverse family of Diptera with approximately 1,600 species worldwide, some of which are agricultural pests. Although mtCOI barcode analyses have been performed on Hylemya nigrimana (Meigen, 1826), the mitogenome of this taxon has not been assembled and analysed. Here, the complete mitogenome of H. nigrimana was sequenced and analysed to confirm the systematic and phylogenetic history of this species. The mitogenome is 16,746 bp long with high A+T content, and consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a noncoding control region. Our result provided a valuable genomic data for contributions to the evolutionary history of Anthomyiidae.

Dimensional Regulation in Metal‐Free Perovskites by Compositional Engineering to Achieve Record Low X‐ray Detection Limits

Utilizing the manipulation of perovskite dimensions has been proven as an effective approach in regulating perovskite properties. Nevertheless, achieving precise control over the dimensions of perovskites within the same system poses a significant challenge. In this study, we introduce a sophisticated method to attain precise dimensional control in metal‐free perovskites (MFPs), specifically through the process of octahedron tailoring by compositional engineering. Accordingly, we successfully instigated a transition from HPIP‐NH4I3⋅H2O (3D), HPIP2‐NH4I5 (2D) and HPIP3‐NH4I7 (1D) structures. Notably, HPIP2‐NH4I5 is the first 2D MFP. As anticipated, these perovskites exhibited completely distinct fluorescence and X‐ray detection capabilities due to their differing dimensions. Remarkably, the 2D HPIP2‐NH4I5 device effectively hindered ion migration perpendicular to the 2D layers, achieving the lowest detection limit of 12.2 nGyairs‐1 among metal‐free single crystals‐based detectors. This study expands the dimensionality control strategies for MFPs and introduces, for the first time, the potential of 2D MFPs as high‐performance X‐ray detectors, thereby enriching the diversity of the MFPs family.

Dimensional Regulation in Metal-Free Perovskites by Compositional Engineering to Achieve Record Low X-ray Detection Limits.

Utilizing the manipulation of perovskite dimensions has been proven as an effective approach in regulating perovskite properties. Nevertheless, achieving precise control over the dimensions of perovskites within the same system poses a significant challenge. In this study, we introduce a sophisticated method to attain precise dimensional control in metal-free perovskites (MFPs), specifically through the process of octahedron tailoring by compositional engineering. Accordingly, we successfully instigated a transition from HPIP-NH4I3⋅H2O (3D), HPIP2-NH4I5 (2D) and HPIP3-NH4I7 (1D) structures. Notably, HPIP2-NH4I5 is the first 2D MFP. As anticipated, these perovskites exhibited completely distinct fluorescence and X-ray detection capabilities due to their differing dimensions. Remarkably, the 2D HPIP2-NH4I5 device effectively hindered ion migration perpendicular to the 2D layers, achieving the lowest detection limit of 12.2 nGyairs-1 among metal-free single crystals-based detectors. This study expands the dimensionality control strategies for MFPs and introduces, for the first time, the potential of 2D MFPs as high-performance X-ray detectors, thereby enriching the diversity of the MFPs family.

ß‐Phenethylamine Synthesis via Latent Dual Electrophilicity of N‐Pyridinium Aziridines

ß‐Phenethylamines are widely represented in biologically and pharmacologically active organic small molecules. Here, we introduce N‐pyridinium aziridines as latent dual electrophiles for the synthesis of ß‐phenethylamines. Bromide‐promoted ring opening generates ß‐halopyridinium amines. Selective Ni‐catalyzed C–C cross‐coupling between organozinc nucleophiles and the benzylic C–Br electrophile affords a diverse family of ß‐functionalized phenethylaminopyridinium salts, and coupling is stereoconvergent in the presence of chiral ligands. Subsequent Ni‐catalyzed reductive N–N bond activation within the b‐functionalized phenethylamino‐pyridinium salts furnishes the products of formal olefin carboamination. Other reductive N–N cleavage reactions are demonstrated to provide access to free primary amines, alkylated amines, heterocycles, and products derived from N‐centered radical chemistry. The developed reaction sequence can be implemented in the context of complex molecules and natural product derivatives. Together, the described results provide a general and modular synthesis of ß‐phenethylamines and significantly expand the utility of N‐pyridinium aziridines as linchpins in chemical synthesis

ß-Phenethylamine Synthesis via Latent Dual Electrophilicity of N-Pyridinium Aziridines.

ß-Phenethylamines are widely represented in biologically and pharmacologically active organic small molecules. Here, we introduce N-pyridinium aziridines as latent dual electrophiles for the synthesis of ß-phenethylamines. Bromide-promoted ring opening generates ß-halopyridinium amines. Selective Ni-catalyzed C-C cross-coupling between organozinc nucleophiles and the benzylic C-Br electrophile affords a diverse family of ß-functionalized phenethylaminopyridinium salts, and coupling is stereoconvergent in the presence of chiral ligands. Subsequent Ni-catalyzed reductive N-N bond activation within the b-functionalized phenethylamino-pyridinium salts furnishes the products of formal olefin carboamination. Other reductive N-N cleavage reactions are demonstrated to provide access to free primary amines, alkylated amines, heterocycles, and products derived from N-centered radical chemistry. The developed reaction sequence can be implemented in the context of complex molecules and natural product derivatives. Together, the described results provide a general and modular synthesis of ß-phenethylamines and significantly expand the utility of N-pyridinium aziridines as linchpins in chemical synthesis.