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The polymerization of myosin molecules into thick filaments in muscle sarcomeres is essential for cardiac contractility, with the attenuation of interactions between the heads of myosin molecules within the filaments being proposed to result in hypercontractility, as observed in hypertrophic cardiomyopathy (HCM). However, experimental evidence demonstrates that the structure of these giant macromolecular complexes is highly dynamic, with molecules exchanging between the filaments and a pool of soluble molecules on the minute timescale. Therefore, we sought to test the hypothesis that the enhancement of interactions between the heads of myosin molecules within thick filaments limits the mobility of myosin by taking advantage of mavacamten, a small molecule approved for the treatment of HCM. Myosin molecules were labeled in vivo with a green fluorescent protein (GFP) and imaged in intact hearts using multiphoton microscopy. Treatment of the intact hearts with mavacamten resulted in an unexpected > 5-fold enhancement in GFP-myosin mobility within the sarcomere. In vitro biochemical assays suggested that mavacamten enhanced the mobility of GFP-myosin by increasing the solubility of myosin molecules, through the stabilization of a compact/folded conformation of the molecules, once disassociated from the thick filaments. These findings provide alternative insight into the mechanisms by which molecules exchange into and out of thick filaments and have implications for how mavacamten may affect cardiac contractility.

Site‐selective C−H bond functionalization of arenes at the para position remains extremely challenging primarily due to its relative inaccessibility from the catalytic site. As a consequence, it is significantly restricted to limited molecular scaffolds. Herein, we report a method for the para‐C−H borylation of aromatic aldimines and benzylamines using commercially available ligands under iridium catalysis. The established method displays excellent para selectivity for variously substituted aromatic aldimines, benzylamines and bioactive molecules. Based on several control experiments, it is proposed that a Lewis acid−base interaction between the nitrogen and boron functionality guides the para selectivity via a steric shield for the aromatic aldimines, where Bpin acts as a transient directing group. However, the steric shield of the in situ generated N−Bpin moiety controlled the overall selectivity for the para borylation of benzylamines. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) and their applications in photocatalysis have been extensively studied, but the instability of imine‐linked COFs is an important factor limiting their performance. In this work, two imine‐linked COFs were successfully converted to amide‐linked COFs through post synthetic modification (PSM). The oxidized COFs presented lower binding energy to O2, exhibited higher photocatalytic activity for oxidation of thioethers and coupling of benzylamines with excellent stability. The present work can serve as a reliable reference for the development of novel highly active and stable COF‐based photocatalysts. [ABSTRACT FROM AUTHOR]

A tandem one-pot synthesis of some novel 1,3-bis substituted-2-isopropylamidines is reported. The conversion involves the base-mediated tandem acylation of benzylamines with isobutyryl chloride in DCM, and the subsequent amidation of the amide intermediate generated in situ in POCl3 in a nitrogen atmosphere. In-silico ADME and drug-likeness prediction showed good pharmacokinetic properties. Molecular docking was performed to assess the binding affinities of the purified 1,3-bis substituted-2-isopropylamidines with a wide range of protein targets of pathological significance. Among the synthesized molecules, compound 5b showed the highest binding affinity (−10.5 kcal mol−1) with the cdk2 receptor, an important cancer progression receptor. The best pose of the 5b-cdk2 complex was further used in simulation studies of the molecular dynamics. The stability of the protein–ligand complex was theoretically assessed in the simulations of the molecular dynamics using RMSD, RMSF, and analysis of hydrogen bonds. [ABSTRACT FROM AUTHOR]

We report an efficient protocol for oxidation of primary/secondary benzyl alcohols and benzylamines to produce corresponding aldehydes or ketones. Our unified method involves the use of commercially available (diethylamino)sulfur trifluoride (DAST) as a reagent combined with DMSO as solvent and oxidant. The reaction provided corresponding carbonyl compounds in good to excellent yields with high purity and in short reaction times. [ABSTRACT FROM AUTHOR]

This work involved synthesizing three N‐benzyl‐4‐hydroxybenzylamines using indirect reductive amination of aromatic aldehydes and 4‐hydroxybenzylamine. Such benzylamines' reaction with formaldehyde produced tricyclic azacyclophanes formed by two benzylamine units joined by methylene bridges. Computational calculations established that macrocyclization was promoted by template formation stabilized by hydrogen bonds and π‐stacking. [ABSTRACT FROM AUTHOR]

Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.

Covalent organic framework (COF) nanosheets have recently garnered great attention as a new class of functional materials. As one of the sustainable processes, however, the photocatalytic organic synthesis in water has not been investigated using COF nanosheets as a photocatalyst to date. Herein, we reported the synthesis of a fully conjugated COF nanosheets with carboxyl functional group through a cooperative strategy of chemical exfoliation and group transformation. The new COF nanosheets was found to be an efficient heterogeneous photocatalyst for a wide range of organic synthesis including selective oxidation of sulfides and oxidative coupling of benzylamines in water under visible–light illumination. This work contributes a new roadmap for the design and synthesis of functional COF–based nanosheets, but also further extends the application boundary of the ultrathin COF nanosheets. [ABSTRACT FROM AUTHOR]

A series of mixed N‐heterocylic carbene (NHC) palladium complexes bearing C^N bidentate ligands derived from benzylamine, phenethylamine, and biphenylamine were prepared and fully characterized by NMR spectroscopy, ESI‐MS spectrometry, and X‐ray diffraction analyses. The complexes were potent in inhibiting proliferation of HepG2 and Caco2 cancer cells, and a SAR (structure–activity relationship) study revealed C^N ligands with stronger electron donation and moderate steric hindrance are more cytotoxic. DNA binding study through UV–vis absorption titration indicated that such complexes bound stronger to CT‐DNA molecules with higher binding constants. Additional molecular docking of the best performer suggested a groove binding mode through hydrogen bonding and π‐π stacking interactions. The apoptosis induced by the two best performers of α,α‐dimethylbenzylamine and S‐α‐methylbenzylamine ligated complexes was further analyzed by morphology change, cell cycle distribution, ROS production, and mitochondrial membrane potential studies. [ABSTRACT FROM AUTHOR]

Routes of modification of 5,6,7,8-tetrafluoro-3-methoxycarbonyl-2-(4-methoxyphenyl)-4H-chromen-4-one and its decarboxylated analogs in the reactions with aliphatic amines were studied and the biological activity of both the starting compounds and the products was tested. It was found that 5,6,7,8-tetrafluoro-3-methoxycarbonyl-2-(4-methoxyphenyl)-4H-chromen-4-one under the action of primary amines underwent the flavone-coumarin rearrangement through the addition of the amine at the C(2) atom. 7-Amino-substituted flavones were formed as by-products in the reactions with methyl- and benzylamines and as major products in the reactions with pyrrolidine. The process of nucleophilic aromatic substitution at the C(7) atom becomes a key one in the reactions of decarboxylated tetrafluoroflavones with primary amines and pyrrolidine. Mechanisms for the studied transformations were proposed. The starting tetrafluoroflavones were found to exhibit high antifungal activity, while antigonorrheal agents were revealed among the products of their transformations. [ABSTRACT FROM AUTHOR]

Indirect reductive amination of aromatic aldehydes was studied in this work; aqueous ammonia was used as a nitrogen source. The results showed that aromatic aldehydes' reaction with aqueous ammonia produced compounds known as hydrobenzamides (N,N´-(phenylmethylene)bis(1-phenylmethanimines), having good yield. The reaction of hydrobenzamides with sodium borohydride reduced both imine and aminal carbons and produced a primary and secondary benzylamine mixture. This article analyses such behaviour and proposes a possible mechanism for explaining such transformation. The reaction of aromatic aldehydes with aqueous ammonia produced compounds known as hydrobenzamides (N,N´-(phenylmethylene)bis(1-phenylmethanimines). The reaction of hydrobenzamides with sodium borohydride reduced both imine and aminal carbons and produced a primary and secondary benzylamine mixture. [ABSTRACT FROM AUTHOR]

BackgroundChemokine receptor CXCR4 antagonist plerixafor (Px) as well as high volume (HV) leukapheresis have been shown to reduce hematopoietic stem progenitor cell (HSPC) mobilization failure rates. However, no direct comparisons of such methods currently exists.Methods and materialsWe compared the HSPC collection yield based on basal peripheral blood CD34+ cell numbers in patients diagnosed with multiple myeloma or non-Hodgkin's lymphoma undergoing autologous stem cell transplantation in a retrospective chart review. The leukapheresis methods used included HV versus regular volume (RV) with or without Px. There were 116 patients in the study group while the historical control group had 34 patients.Results and conclusionsControl group underwent RV leukapheresis without Px. Addition of Px or HV in the study group failed to display significant improvement in CD34+ cell collection yield; however, when basal CD34+ cell numbers were taken into account, both Px + RV and HV without Px increased CD34+ cell collection yield. The collection failure rates of HV without Px group were comparable to Px + RV when the basal CD34+ cell numbers were over 20/μl. Of interest, multivariate linear regression analysis did not detect any significant difference between HV versus Px + RV or other leukapheresis methods in CD34 yields or collection failure rates from a single collection after controlling for other factors (sex, age, or underlying disease). In multivariate analysis, pre apheresis CD34+ cell number was significantly and positively associated with the CD34+ cell yields from a single apheresis. In our studies, the majority of patients can be rescued without Px by HV alone as a potential cost saving approach. In summary, trend in our studies reflects that both Px and HV are capable of reducing the mobilization failure rates except the poorest mobilizers, which will need to be validated in larger studies.

This article discusses the synthesis of benzylamines, which are important compounds in drug discovery. The authors focus on a nickel-catalyzed cross-electrophile coupling method using N-hydroxyphthalimide esters, which yields good results and is compatible with various functional groups. The method is valuable for medicinal chemistry research and can be carried out under mild conditions using commercially available precursors. The authors acknowledge the support of the Genentech Undergraduate Summer Internship Program and dedicate the article to the late Prof. Keith Fagnou. Supporting information for the article is available online. [Extracted from the article]

The photocatalytic production of fuels and chemicals utilizing highly effective catalysts has garnered a lot of interest as a sustainable and clean strategy. Herein, we have reported the effective fabrication of an imine-linked covalent organic framework, FP-BTA COF, supported 2D–2D MoS2/FP-BTA heterojunction with molybdenum sulfide (MoS2) utilizing an easy hydrothermal technique. The development of a 2D–2D heterojunction between a covalent organic framework (COF) and molybdenum sulfide (MoS2) with well-matched band positions can efficiently restrict the recombination of the charge carriers and boost the light absorption capacity along with the surface area, which is mainly responsible for the greatly improved catalytic efficiency. This as-prepared MoS2/FP-BTA hybrid photocatalyst demonstrated exceptional dual catalytic efficiency for the oxidative coupling of benzylamine derivatives to generate higher yields (92%) of N-benzylidene benzylamines along with selective reduction of carbon dioxide (CO2) to formic acid (highest generation rate = 43.3 mol gcat−1 h−1) at atmospheric carbon dioxide (CO2) pressure as compared to molybdenum sulfide (MoS2) and the FP-BTA COF without the requirement of any extra sacrificial electron donors under sunlight. The present research also focuses on economically viable, straightforward and sustainable methods for visible-light induced oxidation of a sequence of benzylamines under atmospheric oxygen (O2) utilizing the MoS2/FP-BTA hybrid material and the highest 98% isolated yield of the product containing a mixture of the corresponding imine and carbonyl compounds was achieved under ambient reaction conditions. The photocatalyst produced a good amount of the intended products and was easily recoverable and recyclable up to the fifth run for both reactions. The creation of a single hybrid with a 2D–2D interface by fusing organic and inorganic materials as well as the twin strategy of producing valuable chemicals in a single process may open up new prospects for sustainable development and enhance the atom economy. [ABSTRACT FROM AUTHOR]

On Earth and beyond, organic chemistry often occurs in the presence of water within environments that deviate drastically from ambient conditions (25 °C and 1 bar). Accurately predicting aqueous organic reaction pathways is crucial toward understanding planetary scale processes such as the cycling of elements crucial for life (e.g., carbon and nitrogen). Advanced thermodynamic modeling can be utilized to determine the favorability of various organic reactions based on geologically relevant ranges of temperature and pressure, as well as compositional variables (e.g., pH). However, data that would otherwise allow for a diversity of organic compounds and environmental conditions to be modeled are sparse and rarely tested with experiments, particularly with regard to organic-nitrogen compounds. In this work, we develop a framework to estimate thermodynamic properties at ambient conditions that can then be extrapolated across ranges of temperature and pressure for aqueous primary, secondary, and tertiary amines and aminiums (protonated amines), specifically those structures containing linear alkyl chains and benzyl functional groups. We also performed hydrothermal experiments (250 °C, ∼40 bar) involving reactions of methylamines to test our resulting thermodynamic models, and we compare our models for other alkylamines and benzylamines to previous empirical measurements from the literature. Specifically, we use existing thermodynamic data along with our estimates at ambient conditions in combination with a variety of existing extrapolation methods related to the revised Helgeson-Kirkham-Flowers (HKF) equations of state to generate temperature- and pressure-dependent predictions of acid dissociation constants (i.e., p K a values) that strongly agree with previous empirical measurements. We use similar methods to predict product distributions for reactions involving primary, secondary, and tertiary amines/aminiums, as well as ammonia/ammonium and corresponding alcohols whose collective distributions depend on reversible substitution reactions. Our predictions are in good agreement with our experimental results involving the methylamine reaction system as well as previous experiments involving the benzylamine reaction system, for which we also produced thermodynamic estimates involving benzyl alcohol. The agreement between independent theoretical predictions and experimental measurements suggests that our estimated properties can be applied to modeling amine chemistry in other experimental and natural aqueous systems that range in temperature and pressure, providing new tools for planetary exploration. [ABSTRACT FROM AUTHOR]

A photo-induced α-C(sp³)--H decyanative pyridination of N-arylglycine derivatives with cyanopyridines was developed. This reaction was performed under organic photocatalytic and redoxneutral conditions via a radical--radical cross-coupling process. Besides, the protocol was also suitable for the C(sp³)--H pyridination of N-aryl tetrahydroisoquinolines as well as benzylamines. [ABSTRACT FROM AUTHOR]

A three-component organocatalytic reaction of 1,3-dipolar cycloaddition between the in situ generated azomethine ylides and 3-substituted 1,2-diphenylcyclopropenes is described. The azomethine ylides have been generated via condensation of aromatic compounds (such as isatins and acenaphthenequinone) with benzylamines. The reaction has afforded derivatives of 3-azabicyclo[3.1.0]hexane, spiro-fused with the fragments of 2-oxindole and acenaphthylene-1(2H)-one. The cycloadducts have been obtained with yield up to 91%, mainly as individual diastereomers. The influence of bifunctional squaramide-based organocatalysts on the course of these three-component reactions has been investigated. Antiproliferative activity of selected synthesized compounds with respect to the human erythromyelosis (K562) and melanoma (Sk-mel-2) cell lines has been assessed in vitro by means of MTS analysis. [ABSTRACT FROM AUTHOR]

An efficient TBHP/TBAI mediated strategy has been developed for the synthesis of 2,4,6‐trisubstitued pyridines from ketoxime acetates and benzylamines under metal‐free conditions for the first time. In this protocol benzylamine acts as an effective ArCO surrogate. This methodology features use of inexpensive catalysts, avert of additional ligands and additives and high functional group tolerance. Moreover, 5‐Lipoxygenase enzyme inhibitory activities were performed for all synthesised compounds. Among all 2,4,6‐trisubstituted pyridines 3fg, 3fa and 3eg showed good activity. [ABSTRACT FROM AUTHOR]

This study explores a rational synthesis of a molybdenum‐promoted Ce−Si mixed oxide catalyst (MoO3/CeO2−SiO2) to regulate synergies between MoO3 and SiO2 dopant on CeO2, achieving high selectivity in solvent‐free catalytic oxidative coupling of amines to imines using molecular O2 as the oxidant. Comparative efficiency tests were conducted with bare CeO2, CeO2−SiO2, and MoO3/CeO2 catalysts. Characterization techniques, including XRD, Raman spectroscopy, N2‐adsorption‐desorption analysis, FTIR, NH3−TPD, TEM, and XPS, were employed to assess textural properties, acidic features, promoter and dopant dispersion in CeO2 lattice, and oxygen defects. Mo/Ce−Si catalyst exhibited superior acidic sites and a higher concentration of Ce3+ ions (Iu/ITotal), indicating increased oxygen vacancies. This catalyst demonstrated exceptional performance in the oxidative coupling of benzylamine, providing higher conversion and selectivity to the corresponding imine. Remarkably, the Mo/Ce−Si catalyst maintained consistent performance over five recycling runs. The catalyst also proved effective for the selective oxidative coupling of various amine substrates with diverse steric and electronic properties. Experimental results confirmed a plausible reaction mechanism within the concise catalyst design. [ABSTRACT FROM AUTHOR]

The highly efficient reductive amination of aldehydes with ammonia (NH3) and hydrogen (H2) to form secondary imines is described, as well as the dehydrogenative homocoupling of benzyl amines. Using an air-stable, well-defined PN3-manganese(II) pincer complex as a catalyst precursor, various aldehydes are easily converted directly into secondary imines using NH3 as a nitrogen source under H2 in a one-pot reaction. Importantly, the same catalyst facilitates the dehydrogenative homocoupling of various benzylamines, exclusively forming imine products. These reactions are conducted under very mild conditions, without the addition of any additives, yielding excellent selectivities and high yields of secondary imines in a green manner by minimizing wastes. [ABSTRACT FROM AUTHOR]

We have constructed Fe3O4@BAAH-CuCl nanomagnetic catalyst in ChCl-Urea (choline chloride deep eutectic as solvent) as a highly efficient catalytic system for the preparation of 2-aryl quinazoline derivatives through one-pot, three-component reactions of 2-bromobenzaldehyde with primary amines and sodium azide under molecular oxygen. FT-IR, VSM, SEM, TEM, TGA, XRD, EDX, ICP-OES and elemental mapping analyses confirmed the fabrication of Fe3O4@BAAH-CuCl nanomaterial. In this project, we first prepared various derivatives of benzylamines from reduction of aryl nitriles, then used the benzylamine products as substrates in the three-component synthesis of 2-aryl quinazoline derivatives in the presence of Fe3O4@BAAH-CuCl/ChCl-Urea as an efficient catalytic system. Although the synthesized products (primary amines and 2-aryl quinazolines) were known, their physical state was confirmed with the reported samples in the literature and the structure of all the products confirmed by 1HNMR and 1CNMR. [ABSTRACT FROM AUTHOR]

With KI as the supporting electrolyte and a mediator, DMSO as the solvent and KHCO3 as the base, a convenient and efficient electrochemical route was developed for the synthesis of polysubstituted oxazoles from aromatic ketones and benzylamines. The electrosynthesis was smoothly carried out in an undivided cell at room temperature, affording the target products in moderate to high yields. [ABSTRACT FROM AUTHOR]

This article presents a study on the synthesis of primary benzylamines, which are important in medicinal chemistry. The researchers used a photoredox-catalyzed decarboxylative coupling method with aryl halides and glycine derivatives to create these molecules. They discuss the reaction mechanism and provide experimental results, including different reaction conditions and yields. This research contributes to the development of new synthetic procedures for primary benzylamine scaffolds, which could lead to the discovery of new functional molecules. Additionally, the study explores the decarboxylative aminomethylation of aryl bromides with glycine derivatives, testing various reaction conditions and catalysts to optimize product yield. The researchers found that electron-deficient aryl bromides reacted well, and the reaction was applicable to other heteroarenes. They also investigated the impact of different protecting groups on the nitrogen atom. Overall, this study offers an efficient method for synthesizing aminomethylated compounds, which may have potential applications in drug discovery. [Extracted from the article]

An oxidative transformation from N‐substituted benzylamine into the corresponding benzamides was developed here using the oxidative system combined from the catalytic amount of PVP−I (polyinyl pyrrolidone) with TBHP. This newly developed method had the advantages of mild reaction conditions and broad substrate scope. The key intermediate of Enzalutamide as androgen receptor inhibitors was prepared using this catalytic condition starting from commercial available 2‐fluoro‐4‐nitrobenzaldehyde with the yield of 78.5 % for three‐step reactions. [ABSTRACT FROM AUTHOR]

The nuclear receptors liver X receptor (LXR) α and β play crucial roles in hepatic metabolism. Many genes induced in response to pharmacologic LXR agonism have been defined; however, the transcriptional consequences of loss of LXR binding to its genomic targets are less well characterized. Here, we addressed how deletion of both LXRα and LXRβ from mouse liver (LXR double knockout [DKO]) affects the transcriptional regulatory landscape by integrating changes in LXR binding, chromatin accessibility, and gene expression. Many genes involved in fatty acid metabolism showed reduced expression and chromatin accessibility at their intergenic and intronic regions in LXRDKO livers. Genes that were up-regulated with LXR deletion had increased chromatin accessibility at their promoter regions and were enriched for functions not linked to lipid metabolism. Loss of LXR binding in liver reduced the activity of a broad set of hepatic transcription factors, inferred through changes in motif accessibility. By contrast, accessibility at promoter nuclear factor Y (NF-Y) motifs was increased in the absence of LXR. Unexpectedly, we also defined a small set of LXR targets for direct ligand-dependent repression. These genes have LXR-binding sites but showed increased expression in LXRDKO liver and reduced expression in response to the LXR agonist. In summary, the binding of LXRs to the hepatic genome has broad effects on the transcriptional landscape that extend beyond its canonical function as an activator of lipid metabolic genes.

Benzylamine is a valuable intermediate in the synthesis of organic compounds such as curing agents and antifungal drugs. To improve the efficiency of benzylamine biosynthesis, we identified the enzymes involved in the multi-enzyme cascade, regulated the expression strength by using RBS engineering in Escherichia coli, and established a regeneration-recycling system for alanine. This is a cosubstrate, coupled to cascade reactions, which resulted in E. coli RARE-TP and can synthesize benzylamine using phenylalanine as a precursor. By optimizing the supply of cosubstrates alanine and ammonia, the yield of benzylamine produced by whole-cell catalysis was increased by 1.5-fold and 2.7-fold, respectively, and the final concentration reached 6.21 mM. In conclusion, we achieved conversion from L -phenylalanine to benzylamine and increased the yield through enzyme screening, expression regulation, and whole-cell catalytic system optimization. This demonstrated a green and sustainable benzylamine synthesis method, which provides a reference and additional information for benzylamine biosynthesis research. The enzyme cascade in E. coli BL21 (DE3) RARE for the synthesis of benzylamine. [ABSTRACT FROM AUTHOR]

Spiropyran (SP)‐based dynamic materials undergo structural changes in response to external stimuli. In this paper, we show that digital holographic microscopy (DHM) is an effective candidate for characterisation of SPs (embedded in polymer matrices) and for monitoring of their dynamical changes. The polymer matrices are polylactic acid (PLA) and poly(methyl methacrylate) (PMMA) films, which are decorated with SPs and immobilised on graphene quantum dots (GQDs). GQDs are modified by benzylamines prior to the loading of SP species because of the enhancement of hydrophobic characteristics. UV irradiation is used as the external stimulus and the dynamical changes of the samples before and after UV irradiation are measured. DHM is arranged on a novel self‐referencing setup, which substantially reduces the sensitivity of DHM to environmental vibrations. Morphometric information for characterisation of the samples is obtained by analysis of the recorded digital holograms. The experimental results demonstrate the potential of the presented technique to serve as an alternative technique for surface measurement methodologies such as atomic force microscope and stylus profiler for surface characterisation of similar materials. [ABSTRACT FROM AUTHOR]

An available method for a synthesis of N-substituted (E)-2-(diphenylphosphoryl)aziridines with high yields by the reaction of (1,2-dibromoethyl)(diphenyl)phosphine oxide with a number of primary amines, in particular, methyl-, ethyl-, isopropyl-, tert-butyl-, cyclohexyl- and benzylamines at room temperature in the presence of sodium hydroxide, has been developed. The antibacterial activity of the synthesized compounds was evaluated. [ABSTRACT FROM AUTHOR]

Photocatalysis is accepted as a promising method for selective oxidative coupling of amine to imine. However, owing to the rapid dehydrogenation of the generated imine intermediate of α‐amino hydrogen to butyronitrile, it remains a huge challenge to fabricate an exquisite catalyst with enhanced conversion and selectivity. Herein, a novel heterogeneous catalyst (Bpy‐CoCl2/CNCOOH) is developed, where carboxyl functionalized carbon nitride (CNCOOH) serves as a substrate material and couples with highly efficient cobalt‐aminopyridine (Bpy‐CoCl2) molecular catalyst through covalent bonding. The catalyst not only effectively facilitates the transfer of photogenerated charges, but also generates mildly oxidatively active species of superoxide radicals, which can effectively oxidize various functionalized benzylamines to corresponding imines in the presence of oxygen with at least 78.5% conversion and >99% selectivity using O2 as oxygen source, especially for the unmodified benzylamine with >99% conversion and >99% selectivity. This unique combination of a selective molecular catalyst and a simple and robust semiconducting material open new avenues for the selective oxidative coupling of amines. [ABSTRACT FROM AUTHOR]

An efficient method for the synthesis of 2,4,6-triaryl pyridines is disclosed. Singlet molecular oxygen generated from trans-5-hydroperoxy-3,5-dimethyl-1,2-dioxolane-3-yl ethaneperoxate has been explored as an effective oxidant for oxidative cleavage of C-N bond in the synthesis of 2,4,6-trisubstituted pyridines from benzylamines and aryl methyl ketones. The convenient preparation of the reagent, simple reaction procedures, avoidance of transition metal catalysts, good-to-excellent yields, short reaction times, and synthesis of asymmetric pyridine derivate are some of the advantages of this protocol. Thus, this protocol may serve as a potential synthetic method for the synthesis of 2,4,6-trisubstituted pyridines. Singlet molecular oxygen generated from trans-5-hydroperoxy-3,5-dimethyl-1,2-dioxolane-3-yl ethaneperoxate/n-Bu4NF has been explored as an effective oxidant for oxidative cleavage of C-N bond in the synthesis of 2,4,6-trisubstituted pyridines. The avoidance of transition metal catalysts, good-to-excellent yields, and synthesis of symmetric and asymmetric pyridine derivates are some of the advantages of this protocol. [ABSTRACT FROM AUTHOR]

The reaction of [Ru(PPh3)3Cl2] with a group of four 1,4-diazabutadiene ligands (p-RC6H4N＝C(H)–C(H)＝NC6H4R-p; R = OCH3, CH3, H and Cl; abbreviated as L-R) in an equimolar ratio afforded chloro-bridged di-ruthenium complexes (1–4) of the general type [Ru2(PPh3)2(L-R)2Cl3]Cl. The crystal structures of complexes 1 (R = OCH3), 2 (R = CH3) and 4 (R = Cl) were determined and the molecular structure of complex 3 (R = H) was optimized using the DFT method. Each complex showed four intense absorptions in the visible and ultraviolet regions, the origin of which was probed employing TDDFT calculations. The complexes were found to serve as efficient catalyst precursors for the oxidative and deaminative C–N coupling of a series of primary amines, producing corresponding imines in good yields. Homo-coupling of benzylamines and cross-coupling of two differently substituted benzylamines or benzylamine with anilines and other aryl/alkyl amines could be realized using this catalytic protocol with aerial oxygen as the oxidant. [ABSTRACT FROM AUTHOR]

Chiral diarylmethylamines (DAMA) are important structural motifs widely present in pharmaceuticals, natural products, and chiral ligands. Herein, we reported a highly enantioselective synthesis of chiral DAMAs via cobalt‐catalyzed enantioselective C−H alkoxylation strategy. The reaction features easy operation, the use of earth‐abundant and cost‐efficient cobalt(II) catalyst, and readily available ligand. A range of chiral DAMAs were efficiently synthesized in high yields with excellent enantioselectivities (up to 90 % yield and up to 99 % ee) through desymmetrization and parallel kinetic resolution. Moreover, this protocol was also compatible with the synthesis of chiral benzylamines via kinetic resolution. [ABSTRACT FROM AUTHOR]

A novel heterojunction material constructed with titanium dioxide nanoparticles and covalent organic frameworks, TiO2@COF‐5 NPs, was designed and synthesized successfully from HHTP, PBBA and TiO2 under solvothermal conditions. Notably, the TiO2@COF‐5 heterojunction demonstrated excellent photocatalytic performance for the aerobic oxidative coupling reaction of benzylamines to N‐benzyl‐1‐phenyl methanimines under visible light irradiation, and both high conversions (up to 99 %) and high selectivity (99 %) were achieved for various benzylamines. The ameliorated photocatalytic performance might owe much to establishing the systematic coupling between the TiO2 nanoparticles and covalent organic frameworks, which could effectively extend the wavelength range of visible light absorption and increase more reactive active sites. This study might provide a versatile approach to combining covalent organic frameworks with inorganic semiconductors to give full play to the synergistic effect of catalysis. [ABSTRACT FROM AUTHOR]

The reaction between N‐(benzylidene)benzylamines (p‐RC6H4CH=NCH2C6H5; R = Cl, H, NO2, F, OMe), [RuCl2(η6‐p‐cymene)]2 and potassium acetate has cleanly furnished the corresponding cycloruthenated complexes C1–C5. The process is completely regioselective, with the formation in all cases of the endo‐derivative, independently of the substituent of the aromatic ring. The five‐membered endo‐metallacycles C6 and C7 can also be obtained from the enantiopure imines (RC)‐p‐RC6H4CH=NCHMeC10H7 (R = Cl, H, respectively) working under similar conditions. The crystal structures of the seven metallated compounds have been determined by X‐ray diffraction. These complexes are active as catalyst precursors for the reduction of acetophenone and benzophenone by transfer hydrogenation. An enantiomeric excess of up to 77% at room temperature has been obtained with the complex C7 in the reduction of acetophenone. [ABSTRACT FROM AUTHOR]

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3)−H functionalization by hydrogen‐atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods for intermolecular enantioselective C(sp3)−H amination remain elusive. Herein, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp3)−H amination with peroxide as an oxidant. This mild, straightforward method can be used to transform an array of feedstock alkylarenes and amides into chiral amines with high enantioselectivities, and it has good functional group tolerance and broad substrate scope. More importantly, it can be used to synthesize bioactive molecules, including chiral drugs. Preliminary mechanistic studies indicate that the amination reaction involves benzylic radicals generated by hydrogen‐atom transfer. [ABSTRACT FROM AUTHOR]

Chemokines play critical roles in numerous physiologic and pathologic processes through their action on seven-transmembrane (TM) receptors. The N-terminal domain of chemokines, which is a key determinant of signaling via its binding within a pocket formed by receptors' TM helices, can be the target of proteolytic processing. An illustrative case of this regulatory mechanism is the natural processing of CXCL12 that generates chemokine variants lacking the first two N-terminal residues. Whereas such truncated variants behave as antagonists of CXCR4, the canonical G protein-coupled receptor of CXCL12, they are agonists of the atypical chemokine receptor 3 (ACKR3/CXCR7), suggesting the implication of different structural determinants in the complexes formed between CXCL12 and its two receptors. Recent analyses have suggested that the CXCL12 N-terminus first engages the TM helices of ACKR3 followed by the receptor N-terminus wrapping around the chemokine core. Here we investigated the first stage of ACKR3-CXCL12 interactions by comparing the activity of substituted or N-terminally truncated variants of CXCL12 toward CXCR4 and ACKR3. We showed that modification of the first two N-terminal residues of the chemokine (K1R or P2G) does not alter the ability of CXCL12 to activate ACKR3. Our results also identified the K1R variant as a G protein-biased agonist of CXCR4. Comparative molecular dynamics simulations of the complexes formed by ACKR3 either with CXCL12 or with the P2G variant identified interactions between the N-terminal 2-4 residues of CXCL12 and a pocket formed by receptor's TM helices 2, 6, and 7 as critical determinants for ACKR3 activation.

Iridium-catalysed regioselective C–H alkynylation of unprotected primary benzylamines and aliphatic aldehydes has been achieved using in situ-installed aldimine directing groups. This protocol provides a straightforward route for the synthesis of the alkynylated primary benzylamine and aliphatic aldehyde derivatives, featuring good substrate compatibility and high regioselectivity. [ABSTRACT FROM AUTHOR]

Using benzylamines as the C4 source of 1,4‐dihydropyridines (1,4‐DHPs), a Cu‐catalyzed oxidative [1+2+1+2] cascade cyclization for the synthesis of 1,4‐DHPs was firstly developed. A broad range of easily available N,N‐dimethyl enaminones and benzylamines are employed smoothly to provide a diverse range of 1,4‐DHPs with high efficiency. This method is performed by a one‐pot cascade C(sp3)−H bond functionalization/C(sp3)−N cleavage/cyclization strategy to form simultaneously two C(sp3)−C(sp2) bonds, two C(sp2)−N bonds, and a 1,4‐DHP ring. [ABSTRACT FROM AUTHOR]

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3)−H functionalization by hydrogen‐atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods for intermolecular enantioselective C(sp3)−H amination remain elusive. Herein, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp3)−H amination with peroxide as an oxidant. This mild, straightforward method can be used to transform an array of feedstock alkylarenes and amides into chiral amines with high enantioselectivities, and it has good functional group tolerance and broad substrate scope. More importantly, it can be used to synthesize bioactive molecules, including chiral drugs. Preliminary mechanistic studies indicate that the amination reaction involves benzylic radicals generated by hydrogen‐atom transfer. [ABSTRACT FROM AUTHOR]

A practical, transition metal‐free method allows the enantioselective synthesis of α,α‐diarylmethylamines by asymmetric α‐arylation of benzylamines. Enantioselective lithiation of N′‐aryl‐N‐benzyl‐N‐isopropyl ureas using a chiral lithium amide base generates a benzyllithium that undergoes an unactivated stereospecific intramolecular nucleophilic aromatic substitution to generate an α,α‐diarylmethylamine in the form of its urea derivative, in up to >99 % ee. Treatment with acid induces an "azatropic shift" with retention of configuration, the product of which may be hydrolysed to the target amine. [ABSTRACT FROM AUTHOR]

A method for direct access to enantioenriched benzylic amides and carbamate‐protected primary benzylamines by C−H functionalization is reported. The C−H substrate is used as limiting reagent with only a small excess of the unactivated amide or carbamate nucleophile. The enantioselective intermolecular dehydrogenative C−N bond formation is enabled by a combination of a chiral copper catalyst, a photocatalyst, and an oxidant, and it takes place under mild conditions, which allow for a broad substrate scope. The method is compatible with late‐stage C−H functionalization, and it provides easy access to 15N‐labeled amides and amines starting from cheap 15NH4Cl. [ABSTRACT FROM AUTHOR]

The synthesis of 2‐oxazolidinones from a three component coupling reaction of amines, epoxides, and CO2. The reaction proceeds in the presence of 1,1,3,3‐tetramethylguanidine under visible light irradiation at atmospheric pressure. The optimized structures of all species involved in the reaction mechanism along with transition states have been described based on the DFT calculations. The developed methodology represents a promising approach of employing CO2 as a naturally abundant and non‐toxic carbon resource to produce profitable chemicals. [ABSTRACT FROM AUTHOR]

The synthesis of 2‐oxazolidinones from a three component coupling reaction of amines, epoxides, and CO2. The reaction proceeds in the presence of 1,1,3,3‐tetramethylguanidine under visible light irradiation at atmospheric pressure. The optimized structures of all species involved in the reaction mechanism along with transition states have been described based on the DFT calculations. The developed methodology represents a promising approach of employing CO2 as a naturally abundant and non‐toxic carbon resource to produce profitable chemicals. [ABSTRACT FROM AUTHOR]

Zeolitic imidazolate frameworks (ZIFs) have been extensively examined for their potential in acid–base catalysis. Many studies have demonstrated that ZIFs possess unique structural and physicochemical properties that allow them to demonstrate high activity and yield products with high selectivity. Herein, we highlight the nature of ZIFs in terms of their chemical formulation and the textural, acid–base, and morphological properties that strongly affect their catalytic performance. Our primary focus is the application of spectroscopic methods as instruments for analyzing the nature of active sites because these methods can allow an understanding of unusual catalytic behavior from the perspective of the structure–property–activity relationship. We examine several reactions, such as condensation reactions (the Knoevenagel condensation and Friedländer reactions), the cycloaddition of CO2 to epoxides, the synthesis of propylene glycol methyl ether from propylene oxide and methanol, and the cascade redox condensation of 2-nitroanilines with benzylamines. These examples illustrate the broad range of potentially promising applications of Zn–ZIFs as heterogeneous catalysts. [ABSTRACT FROM AUTHOR]

A novel and efficient method has been developed for the direct synthesis of substituted imidazoles through the reaction of styrenes and benzylamines with the assistance of I2-DMSO concerted system. The reactions proceed efficiently under open air and solvent-free conditions to afford a wide variety of substituted imidazoles in good yields. A productive large-scale synthesis also has been performed to target highly substituted heterocyclic motifs. The present protocol offers metal- and solvent-free process, mild conditions, easily accessible reactants, and operational simplicity to achieve an assembly of substituted N-heterocyclic compounds. [ABSTRACT FROM AUTHOR]

A method for the synthesis of isoindoline derivatives was developed based on a domino reaction involving a donor-acceptor cyclopropane containing a bromomethyl group in the ortho position of the aromatic substituent and structurally varied primary amines (anilines, benzylamines, cycloalkylamines). It was shown that the resulting N-benzyl-1,3-dihydroisoindole under hydrogenolysis conditions at room temperature underwent selective cleavage of the exocyclic N–CH2Ar bond followed by in situ lactamization to form benzo[b]pyrrolizidinone. The same product was obtained in a domino reaction starting with reduction of the azidomethyl group at the ortho position of the donor aromatic substituent. Similarly, the generation of the o-2-aminoethyl group was accompanied by two successive cyclization reactions leading to the formation of benzo[e]indolizidinone. [ABSTRACT FROM AUTHOR]

In this research, the synthesis, photochemistry, and computational study of new cis- and trans-isomers of amino-thienostilbenes is performed to test the efficiency of their production and acid resistance, and to investigate their electronic structure, photoreactivity, photophysical characteristics, and potential biological activity. The electronic structure and conformations of synthesized thienostilbene amines and their photocyclization products are examined computationally, along with molecular modeling of amines possessing two thiophene rings that showed inhibitory potential toward cholinesterases. New amino-styryl thiophenes, with favorable photophysical properties and proven acid resistance, represent model compounds for their water-soluble ammonium salts as potential styryl optical dyes. The comparison with organic dyes possessing a trans-aminostilbene subunit as the scaffold shows that the newly synthesized trans-aminostilbenes have very similar absorbance wavelengths. Furthermore, their functionalized cis-isomers and photocyclization products are good candidates for cholinesterase inhibitors because of the structural similarity of the molecular skeleton to some already proven bioactive derivatives. [ABSTRACT FROM AUTHOR]

We developed a straightforward synthetic route to pharmacologically important 1,5-substituted pyrrolidin-2-ones from donor–acceptor cyclopropanes bearing an ester group as one of the acceptor substituents. This method includes a Lewis acid-catalyzed opening of the donor–acceptor cyclopropane with primary amines (anilines, benzylamines, etc.) to γ-amino esters, followed by in situ lactamization and dealkoxycarbonylation. The reaction has a broad scope of applicability; a variety of substituted anilines, benzylamines, and other primary amines as well as a wide range of donor–acceptor cyclopropanes bearing (hetero)aromatic or alkenyl donor groups and various acceptor substituents can be involved in this transformation. In this process, donor–acceptor cyclopropanes react as 1,4-C,C-dielectrophiles, and amines react as 1,1-dinucleophiles. The resulting di- and trisubstituted pyrrolidin-2-ones can be also used in subsequent chemistry to obtain various nitrogen-containing polycyclic compounds of interest to medicinal chemistry and pharmacology, such as benz[g]indolizidine derivatives. [ABSTRACT FROM AUTHOR]

Two POM-MOFs Co-1 and Ni-1 were synthesized from pyridyl-Anderson-POM linker. When combined with [Ru(bpy) 3 ]2+, Ru(bpy) 3 @Co-1 showed excellent photocatalytic performance in sulfide oxidation and oxidative coupling of benzylamines with good recyclability. [Display omitted] • Two POM-MOFs were synthesized employing a pyridyl-Anderson-POM metalloligand. • The resultant Ru(bpy) 3 @POM-MOF composite, formed through the electrostatic interaction between the cationic [Ru(bpy) 3 ]2+ and the anionic POM unit, exhibited exceptional photocatalytic efficacy in both sulfide oxidation and the oxidative coupling of benzylamines. [ABSTRACT FROM AUTHOR]

An efficient Rh(III)‐catalyzed free NH2‐assisted C−H activation/cyclization of primary benzylamines with iodinium ylides was first developed. This transformation provides an easy approach to various dihydrophenanthridin‐1‐ones with broad functional group tolerance by using air as a green oxidant. Importantly, some reaction products exhibited some degree of growth inhibition of cancer cells. [ABSTRACT FROM AUTHOR]