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Comprehensive Summary: The synthesis of N‐glycosides has received significant attention due to their crucial role in carbohydrate chemistry. Despite considerable advancements developed in the construction of N‐glycosides, methods for the stereoselective construction of 2‐deoxy‐α‐N‐glycosides are still limited. Herein, we disclosed a nickel‐catalyzed hydroamination of glycals under mild conditions. This transformation could allow for the stereoselective synthesis of an array of 2‐deoxy‐α‐N‐glycosides with excellent α‐stereoselectivity. Nickel‐catalyzed glycosylation reactions, particularly those involving anomeric C(sp3)‐metal bond formation, have proven to be an effective and stereoselective strategy for producing various N‐glycosides. Additionally, with highlight of the application of this reaction, γ‐sugar amino acid derivatives were synthesized. [ABSTRACT FROM AUTHOR]

A metal-free photoinduced alkynylation of carbamoyl radicals with hypervalent iodine(III) reagents for a facile synthesis of alkynyl amides is described. This protocol features good functional group tolerance and a broad substrate scope for direct synthesis of alkynyl amide derivatives in good to excellent yields under mild and redox-neutral reaction conditions. The synthetic application is demonstrated by the late-stage installation of alkynyl amides into natural products and active pharmaceutical relevant molecules. The mechanistic studies indicated the simultaneous existence of photoredox catalytic and direct photoexcited processes, and the quantum yields confirmed the occurrence of the radical chain propagation process. [ABSTRACT FROM AUTHOR]

Herein, we report on the translation of a small scale ball‐milled amidation protocol into a large scale continuous reactive extrusion process. Critical components to the successful translation were: a) understanding how the different operating parameters of a twin‐screw extruder should be harnessed to control prolonged continuous operation, and b) consideration of the physical form of the input materials. The amidation reaction is applied to 36 amides spanning a variety of physical form combinations (liquid‐liquid, solid–liquid and solid‐solid). Following this learning process, we have developed an understanding for the translation of each physical form combination and demonstrated a 7‐hour reactive extrusion process for the synthesis of an amide on 500 gram scale (1.3 mols of product). [ABSTRACT FROM AUTHOR]

The radical Truce–Smiles rearrangement is a straightforward strategy for incorporating aryl groups into organic molecules for which asymmetric processes remains rare. By employing a readily available and non‐expensive chiral auxiliary, we developed a highly efficient asymmetric photocatalytic acyl and alkyl radical Truce–Smiles rearrangement of α‐substituted acrylamides using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom–transfer photocatalyst, along with aldehydes or C−H containing precursors. The rearranged products exhibited excellent diastereoselectivities (7 : 1 to >98 : 2 d.r.) and chiral auxiliary was easily removed. Mechanistic studies allowed understanding the transformation in which density functional theory (DFT) calculations provided insights into the stereochemistry‐determining step. [ABSTRACT FROM AUTHOR]

The synthesis of amides holds great promise owing to their impeccable contributions as building blocks for highly valued functional derivatives. Herein, we disclose the design, synthesis and crystal structure of a mixed-ligand ruthenium(II) complex, [Ru(η6-Cym)(O,O-PLY)Cl], (1) where Cym = 1-isopropyl-4-methyl-benzene and O,O-PLY = deprotonated form of 9-hydroxy phenalenone (HO,O-PLY). The complex catalyzes the aerobic oxidation of various primary amines (RCH2NH2) to value-added amides (RCONH2) with excellent selectivity and efficiency under relatively mild conditions with common organic functional group tolerance. Structural, electrochemical, spectroscopic, and computational studies substantiate that the synergism between the redox-active ruthenium and π-Lewis acidic PLY moieties facilitate the catalytic oxidation of amines to amides. Additionally, the isolation and characterization of key intermediates during catalysis confirm two successive dehydrogenation steps leading to nitrile, which subsequently transform to the desired amide through hydration. The present synthetic approach is also extended to substitution-dependent tuning at PLY to tune the electronic nature of 1 and to assess substituent-mediated catalytic performance. The effect of substitution at the PLY moiety (5th position) leads to structural isomers, which were further evaluated for the catalytic transformations of amine to amides under similar reaction conditions. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effect of detoxifying substances on U(VI) removal by bacteria isolated from mine soil. The results demonstrated that the highest U(VI) removal efficiency (85.6%) was achieved at pH 6.0 and a temperature of 35 °C, with an initial U(VI) concentration of 10 mg/L. For detoxifying substances, signaling molecules acyl homoserine lactone (AHLs, 0.1 µmol/L), anthraquinone-2, 6-disulfonic acid (AQDS, 1 mmol/L), reduced glutathione (GSH, 0.1 mmol/L), selenium (Se, 1 mg/L), montmorillonite (MT, 1 g/L), and ethylenediaminetetraacetic acid (EDTA, 0.1 mmol/L) substantially enhanced the bacterial U(VI) removal by 34.9%, 37.4%, 54.5%, 35.1%, 32.8%, and 47.8% after 12 h, respectively. This was due to the alleviation of U(VI) toxicity in bacteria through detoxifying substances, as evidenced by lower malondialdehyde (MDA) content and higher superoxide dismutase (SOD) and catalase (CAT) activities for bacteria exposed to U(VI) and detoxifying substances, compared to those exposed to U(VI) alone. FTIR results showed that hydroxyl, carboxyl, phosphorus, and amide groups participated in the U(VI) removal. After exposure to U(VI), the relative abundances of Chryseobacterium and Stenotrophomonas increased by 48.5% and 12.5%, respectively, suggesting their tolerance ability to U(VI). Gene function prediction further demonstrated that the detoxifying substances AHLs alleviate U(VI) toxicity by influencing bacterial metabolism. This study suggests the potential application of detoxifying substances in the U(VI)-containing wastewater treatment through bioremediation. [ABSTRACT FROM AUTHOR]

An engineered tetra‐amide macrocycle is presented, and its conformation and anion recognition properties are investigated. The tetra‐amide macrocycle 1, containing the m‐amino benzoic acid, 1,3‐benzenedicarboxylic acid and m‐xylenedinediamine adopts an envelope‐like conformation in solid‐state, where the m‐xylenedinediamine ring is perpendicular with the molecular plain. The tetra‐amide macrocycle 1 is able to bind anions such as halides, sulphate and phosphate in DMSO (dimethyl sulphoxide) solution. The stabilities of the fluoride (2.6×103 M−1) and chloride (5.6×102 M−1) complexes of 1 in DMSO is higher than that of bromide (66 M−1) and iodide (52 M−1). SO42− complexes of 1 in DMSO is more stable than the HSO4−, NO3− and H2PO4− complexes. Using this information, a quantitative evaluation of the stability of the 1 : 1 complex of 1, for which overall binding energy in the order −123.98 kcal/mol for SO42−was calculated. The strong binding affinity of the tetra‐amide macrocycle 1 toward the SO42− ion can be explained on the basis of non‐covalant interaction like ion−dipole interaction, hydrogen bonding interaction and size selectivity. [ABSTRACT FROM AUTHOR]

Palladium‐catalyzed coupling reactions of small nucleophiles are of great interest, but challenging due to difficulties in selectivity control. Herein, we report the development of a new platform of P,N‐ligands consisting of ylide‐functionalized phosphines with aminophosphonium groups (NYPhos) to address this challenge. These phosphine ligands are easily accessible in a wide structural diversity with highly modular electronic and steric properties. Based on a family of 14 ligands the selective monoarylation of acetone as well as other challenging ketones and amides was accomplished with record‐setting activities even for aryl chlorides at room temperature including late‐stage functionalizations of drug molecules. Moreover, ammonia and other small primary amines could be coupled at mild conditions. Isolation and structure analyses of palladium complexes within the catalytic cycle confirmed that the P,N‐coordination mode is necessary to achieve the observed selectivities. It also demonstrated the facile adjustability of the N‐donor strength, which is beneficial for the targeted design of tailored P,N‐ligands for future applications. [ABSTRACT FROM AUTHOR]

We present a condensation of primary aryl or alkyl amines with S -methyl thiouronium salts to obtain N , N , N ′-trisubstituted amidines. High yields, short reaction times, and a fair substrate scope are the noteworthy features of this protocol. Surprisingly, the reaction of a thiouronium salt with 4-aminopyridine gave 1-(4-methoxybenzoyl)piperidine. [ABSTRACT FROM AUTHOR]

The molecular structure of the tripodal carbamoylmethylphosphine oxide compound diethyl {[(5-[2-(diethoxyphosphoryl)acetamido]-3-{2-[2-(diethoxyphosphoryl)acetamido]ethyl}pentyl)carbamoyl]methyl}phosphonate, C25H52N3O12P3, features six intramolecular hydrogen-bonding interactions. The phosphonate groups have key bond lengths ranging from 1.4696 (12) to 1.4729 (12) Å (P=O), 1.5681 (11) to 1.5811 (12) Å (P—O) and 1.7881 (16) to 1.7936 (16) Å (P—C). Each amide group adopts a nearly perfect trans geometry, and the geometry around each phophorus atom resembles a slightly distorted tetrahedron. [ABSTRACT FROM AUTHOR]

This article explores the synthesis of new amide derivatives of the sesquiterpene aryl-himachalene, a compound found in Atlas cedar oil. The researchers successfully synthesized several amide derivatives using different reaction conditions and acyl chlorides, with good yields. The results highlight the potential for using renewable and readily available natural resources in the production of valuable molecules. The document also provides a general procedure for synthesizing amides and includes data on the yields, physical properties, and analysis of the synthesized amides. The authors declare no conflicts of interest. [Extracted from the article]

To investigate the impact of plasticizer functional groups on starch plasticization, three distinct plasticizers were selected in this study: ethylene glycol (EG), ethylenediamine (EDA), and ethylenebisformamide (EBF). Three models of the plasticizer/starch system were constructed using molecular dynamics (MD) simulations, and the analysis encompassed the computation of mean square displacement (MSD), radial distribution function (RDF), and hydrogen bonding energy for each system. Additionally, the proportions of simulation were used to prepare thermoplastic starch films, which were subsequently subjected to examinations such as DSC, XRD, FT-IR, SEM, and mechanical property testing. Comparative analysis of the simulation data from the three systems and the properties of the manufactured thermoplastic starch (TPS) established that the diverse functional groups of plasticizers significantly influenced starch plasticization. In different plasticizer functional group types, it was observed that hydroxyl groups in EG and amino groups in EDA predominantly form hydrogen bonds with hydroxyl groups in starch molecular chain. In contrast, amide groups in EBF can establish hydrogen bonds not only with hydroxyl groups of starch but also with ether bonds on the starch main chain, thereby resulting in more effective starch plasticization. [ABSTRACT FROM AUTHOR]

This study aims to analyze the degradation behavior and mechanisms of amine-cured epoxy asphalt (EA) under the combined effects of ultraviolet (UV) radiation, oxygen, and temperature. To achieve this, amine-cured epoxy resin (ER) and EAs containing 35%, 45%, and 55% asphalt content were prepared and subjected to simulated UV-based aging. Various analytical techniques were employed to investigate the mechanical properties, microstructure, morphology, and oxidation layer of ER and EAs. The results indicate that after UV-based aging, ER and EAs with 35%–45% asphalt content experienced an increase in mass, a decrease in strength and glass transition temperature. In comparison, EAs with 55% asphalt content exhibited the opposite trends. The elongation and (Tanδ)max of ER and EAs reduced, whereas the storage modulus and hardness at mid to high temperatures rose. At the microstructural level, the degradation of the resin phase was confirmed by changes in ether, ester, and amide groups, whereas the generation of sulfoxide groups was associated with the oxidation of the asphalt phase. Compared with ER, the surface of EA has obvious defects after aging, which is the main reason for the decrease in contact angle. As the asphalt content increases, EAs exhibit higher carbonyl concentration, more profound oxidation, and more obvious performance degradation. This trend suggests that the resin phase mitigates the aging of the asphalt phase by absorbing harmful UV radiation and oxygen. [ABSTRACT FROM AUTHOR]

Purpose: The preoperative assessment of carotid plaques is necessary to render revascularization safe and effective. The aim of this study is to evaluate the usefulness of chemical exchange saturation transfer (CEST)-MRI, particularly amide proton transfer (APT) imaging as a preoperative carotid plaque diagnostic tool. Methods: We recorded the APT signal intensity on concentration maps of 34 patients scheduled for carotid endarterectomy. Plaques were categorized into group A (APT signal intensity ≥ 1.90 E-04; n = 12) and group B (APT signal intensity < 1.90 E-04; n = 22). Excised plaques were subjected to histopathological assessment and, using the classification promulgated by the American Heart Association, they were classified as intraplaque hemorrhage-positive [type VI-positive (tVI+)] and -negative [no intraplaque hemorrhage (tVI−)]. Results: Of the 34 patients, 22 (64.7%) harbored tVI+- and 12 (35.3%) had tVI− plaques. The median APT signals were significantly higher in tVI+- than tIVI− patients (2.43 E-04 (IQR = 0.98–4.00 E-04) vs 0.54 E-04 (IQR = 0.14–1.09 E-04), p <.001). Histopathologically, the number of patients with tVI+ plaques was significantly greater in group A (100%, n = 12) than group B (45%, n = 22) (p <.01). The number of symptomatic patients or asymptomatic patients with worsening stenosis was also significantly greater in group A than group B (75% vs 36%, p <.01). Conclusion: In unstable plaques with intraplaque hemorrhage and in patients with symptoms or progressive stenosis, the ATP signals were significantly elevated. CEST-MRI studies has the potential for the preoperative assessment of the plaques' characteristics. [ABSTRACT FROM AUTHOR]

A drug-delivery system operates by employing a carrier to transport medications into the body, shielding it from degradation and ensuring that it reaches its intended site of action. Hydrogels, known for their biocompatibility and ability to degrade naturally, are utilized as carriers in the process. Prednisolone, a gluco-corticosteroid with diverse anti-inflammatory and antioxidant effects, was encapsulated within a hydrogel derived from natural polysaccharides. This encapsulation aimed not only to enable effective drug delivery, but also to assess the compatibility of the hydrogel with biological systems. The process began with the synthesis of polysaccharide-based hydrogel, followed by loading prednisolone at three different concentrations i.e., 0.01, 0.03 and 0.05%, each subjected for detailed analysis. Fourier-transform infrared analysis identified the presence of an amide group, while X-ray diffraction revealed that the resulting oxidized sodium alginate–chitosan hydrogel structure was amorphous in nature. Examination of the hydrogel's surface demonstrated a soft texture, which indicated its properties. The efficiency of cross-linking for the stability of hydrogel, ranged between 65 and 80% of the concentrations tested. Further investigations are focused on the hydrogel's behaviour. The swelling ratio was assessed over various time intervals, which highlighted that 0.01% concentration as particularly effective, reaching equilibrium after 75 min. Porosity, an important factor influencing drug release kinetics, was observed within the range of 0.1–1% for the three concentrations (0.01, 0.03 and 0.05%). Importantly, biocompatibility of the hydrogel was evaluated using the MTT assay to confirm the viability of cells exposed to the prednisolone-loaded hydrogel. This study showcases the potential of the natural polysaccharide-based hydrogel, encapsulating prednisolone, as a viable candidate for efficient drug delivery with promising biocompatibility for biomedical applications. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Catalytic methylative coupling of internal alkynes and aldehydes/aldimines through regioselective oxidative cyclization promoted by a phosphine–Co complex is presented. Such process constitutes an unprecedented and unique approach for Co‐catalyzed generation of metallacycles that reversed inherent regiochemical biases to furnish a wide range of allylic alcohols and allylic amides bearing a tetrasubstituted alkene in up to 98% yield with high regioselectivity, representing a novel and general strategy for reversal of substrate‐controlled regioselectivity in metal‐catalyzed oxidative cyclization. [ABSTRACT FROM AUTHOR]

We describe a palladium-catalyzed Suzuki-type cross-coupling reaction of 2-pyridyl carbamoyl fluorides with boronic acids, which provides entry to medicinally relevant pyridyl amides. Mechanistic studies, including the synthesis and reactivity of carbamoyl Pd–F complexes, reveal the importance of both the fluoride electrophile and nitrogen directing group for aiding reactivity. [ABSTRACT FROM AUTHOR]

ABSTRACT In this study, an efficient catalytic protocol using CuCoFe2O4@GO (CCF@GO) for the synthesis of amide bond (−CONH−) via direct coupling of carboxylic acids and N,N‐dialkylformamides is presented. The CCF@GO nanocatalyst has been synthesized via a single‐pot solvothermal method, by changing the proportions of copper and cobalt (1:1, 1:3, and 3:1). Catalyst screening, employing a model reaction with benzoic acid and dimethylformamide (DMF), revealed that the 1:1 proportion of CCF@GO catalyst exhibited excellent efficiency, achieving a high conversion (98%) towards amide formation. The enhanced catalytic efficiency observed in CCF@GO catalysts can be ascribed to the uniform distribution of active copper and cobalt species on the graphene oxide support, which possesses a high surface area. Optimization of the reaction was conducted by varying parameters such as temperature, solvent, catalyst loading, and oxidant. The prepared catalyst was characterized using various analytical techniques including XRD, FTIR, XPS, SEM, EDX mapping, and TEM. Furthermore, this heterogeneous nanocatalyst demonstrated recoverability using an external magnet and reused up to five times with just a modest loss of catalytic performance. [ABSTRACT FROM AUTHOR]

The role of the structural similarity in the individual components on the self-assembly process of multi-component systems was studied by analysing the gelation properties of chiral multi-component gels with structurally similar (enantiomers) and non-similar donor or acceptor moieties. The gelation properties of the individual enantiomers, mixed enantiomers, and mixed chiral donor-acceptor compounds were analysed in various solvents. Analysis of the mechanical strength revealed that the mixed chiral gels were stronger compared to other gels in mesitylene; however, a reverse trend was observed for thermal stability. Scanning electron microscopy (SEM) of the dried gels of the mixed enantiomeric and mixed chiral donor-acceptor gels showed morphological changes indicating different self-assembly modes. Powder X-ray analysis revealed that a co-assembled mode was observed for the mixed gels with structurally similar components. However, a self-sorting nature was observed for the mixed chiral donor-acceptor gel, and the charge transfer interaction between the donor and acceptor played a major role in the self-assembly of these mixed gels. We performed computational studies to predict the electronic distribution in the individual chiral molecules. These results demonstrate that altering the structural features of the individual components is one of the key parameters that control the self-assembly modes of multi-component systems. [ABSTRACT FROM AUTHOR]

The present work demonstrates the effective synthesis of amide derivatives of Nα‐protected amino acids and aryl/heteroaryl amines using di‐2‐pyridyl carbonate (2‐DPC) and cat. DMAP mediated coupling reaction. Several coupling methods were employed for the screening of the amides using EDC, HATU, mixed anhydride, T3P, CDI, COMU, DPTC, and 2‐DPC, where 2‐DPC/cat. DMAP method furnished amides with better yields and purity in shorter durations. Seventeen amide derivatives (3 a–3 q) were successfully synthesized using the present protocol and were characterized by NMR, mass and IR spectroscopy. Further, we performed the in‐silico and in‐vitro studies on the synthesized molecules on antifungal and antibacterial activity. Molecular docking studies reveal the binding affinity of protein‐ligand interactions ranging from −6.2 to −11.0 kcal/mol (Aspergillus Niger Esta), −5.9 to −9.9 kcal/mol (DNA gyrase subunit B) and −6.4 to −13.4 kcal/mol (CYP51B). Compounds like 3 d, 3 e, 3 h, 3 i, 3 j and 3 l exhibit the highest antibacterial and antifungal activity when compared to the standards delafloxacin, ketoconazole, and bifonazole in in‐silico studies. Whereas the in‐vitro studies also unveiled good antimicrobial activity with peptide conjugates. The results of antimicrobial activity exhibits in antifungal species show the good activity concentrations in compounds 3 j is 11.2±3.54 μg/mL and 3 l is 10.3±2.76 μg/mL. The anti‐bacterial species exhibit the compound 3 g showing good activity in different concentrations 12±3.08 μg/mL, 12.2±3.04 μg/mL, 12.6±2.78 μg/mL and 12.5±2.98 μg/mL. [ABSTRACT FROM AUTHOR]

We report herein a general one‐pot perfluoroalkylation/dehydrohalogenation protocol for the selective perfluoroalkenylation of silyl dienol ethers in their γ position. Importantly, this methodology is applicable to the synthesis of a wide range of γ‐perfluoroalkenylated enals, enones and α,β‐unsaturated amides. Various perfluoroalkenyl moieties could be efficiently introduced, with an important impact on the E/Z diatereoselectivity of the newly formed fluorinated double bond. [ABSTRACT FROM AUTHOR]

A Cu‐catalyzed multi‐component reaction of trifluoromethylated β‐amino ketones and nitriles using tert‐butyl nitrite as a diazotization reagent has been developed. Under the optimized conditions, N‐trifluoroalkyl amides were obtained with yields up to 87%. Control experiments and computational studies reveal that the reaction proceeds through the generation of diazo, in situ formation of nitrile ylide, water addition and final enol tautomerism. This approach features mild reaction conditions, wide substrate tolerance, and scale‐up applicability, which provides an efficient and practical strategy for amide synthesis. [ABSTRACT FROM AUTHOR]

A novel deoxygenative alkynylation of amides promoted by a synergistic action of a divalent rare-earth element and a transition metal has been developed. In this method, α-alkynyl substituted amines are synthesized from unactivated amides and alkynes in a single transformation. Broad substrate scope and excellent selectivity for C＝O cleavage has been demonstrated. This approach represents a general method for the construction of versatile α-alkynyl substituted amines from unactivated amide bonds. [ABSTRACT FROM AUTHOR]

A novel and highly efficient technique has been demonstrated for the transamidation of N-tert-butoxycarbonyl (N-Boc) activated secondary amides, as well as the direct amidation of esters with amines, resulting in the formation of amide bonds. This technique exhibits exceptional selectivity in cleaving N–C/O–C bonds and utilizes Co@NC as a highly efficient magnetic nano-catalyst. The method stands out for its solvent-free conditions, environmentally friendly catalyst, straightforward work-up, and the ability to easily reclaim (aided by an external magnet) and reuse the catalyst for up to five cycles without significant loss of catalytic activity, showcasing both novelty and efficiency. [ABSTRACT FROM AUTHOR]

Although dearomative functionalizations enable the direct conversion of flat aromatics into precious three‐dimensional architectures, the case for simple arenes remains largely underdeveloped owing to the high aromatic stabilization energy. We herein report a dearomative sequential addition of two nucleophiles to arene π‐bonds through umpolung of chromium–arene complexes. This mode enables divergent dearomative carbonylation reactions of benzene derivatives by tolerating various nucleophiles in combination with alcohols or amines under CO‐gas‐free conditions, thus providing modular access to functionalized esters or amides. The tunable synthesis of 1,3‐ or 1,4‐cyclohexadienes as well as the construction of carbon quaternary centers further highlight the versatility of this dearomatization. Diverse late‐stage modifications and derivatizations towards synthetically challenging and bioactive molecules reveal the synthetic utility. A possible mechanism was proposed based on control experiments and intermediate tracking. [ABSTRACT FROM AUTHOR]

Although dearomative functionalizations enable the direct conversion of flat aromatics into precious three‐dimensional architectures, the case for simple arenes remains largely underdeveloped owing to the high aromatic stabilization energy. We herein report a dearomative sequential addition of two nucleophiles to arene π‐bonds through umpolung of chromium–arene complexes. This mode enables divergent dearomative carbonylation reactions of benzene derivatives by tolerating various nucleophiles in combination with alcohols or amines under CO‐gas‐free conditions, thus providing modular access to functionalized esters or amides. The tunable synthesis of 1,3‐ or 1,4‐cyclohexadienes as well as the construction of carbon quaternary centers further highlight the versatility of this dearomatization. Diverse late‐stage modifications and derivatizations towards synthetically challenging and bioactive molecules reveal the synthetic utility. A possible mechanism was proposed based on control experiments and intermediate tracking. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a critical condition with a wide range of triggers that cause heavy burden on public health. Despite its high incidence and mortality, the treatment of AKI still highly relies on hemodialysis, which is costly and usually accompanied by severe complications. Therefore, development of new therapeutic targets and methods for AKI is urgently needed. Herein, a ferroptosis‐targeting strategy for AKI treatment by rationally designed ferroptosis‐inhibitive polypeptide‐based polymersomes (polypeptosomes, FIPs) is proposed. Such FIPs are self‐assembled from poly(glutamic acid)‐block‐poly(methionine‐stat‐tyrosine) [PGA9‐b‐P(Met8‐stat‐PTyr13)]. The ferroptosis‐inhibition function of the FIPs arises from the rationally‐selected amino acid composition: P(Met‐stat‐Tyr) endows the FIPs with a high scavenging efficiency of over 90% toward different reactive oxygen species (ROS); while the glutamate and tyrosine residues, as well as the amide groups, can bind iron ions, thus blocking iron overload and lipid peroxide in cells. In vivo experiments confirm that the FIPs can effectively alleviate oxidative stress, inhibit ferroptosis, and restore kidney functions. Transcriptome sequencing further reveals the therapeutic mechanisms of FIPs. Overall, such polypeptosomes capable of blocking multiple pathways of ferroptosis open a new avenue for AKI treatment and provide fresh insights into the development of generalized therapies for inflammation. [ABSTRACT FROM AUTHOR]

A catalytic asymmetric vinylogous aldol reaction between β,γ-unsaturated amides and isatins has been developed. In the presence of 10 mol% of tertiary amine-thiourea C7, the vinylogous reaction has been achieved in up to 98% yield and up to 99% ee (26 examples). This methodology provides an efficient approach to construct chiral multifunctional 3-hydroxy-2-oxindoles. Moreover, the transformations of the chiral products, including the esterification of amides, the hydrogenation of the C–C double bond and further conversion to spirolactones, have been investigated. [ABSTRACT FROM AUTHOR]

A stereoselective synthesis of the C1–C13 segment of poecillastrin C has been achieved. The C1–C4 moiety was derived from diallyl l -tartrate, and the amide group at the C3 position was constructed by means of a traceless Staudinger reaction. The C1–C13 segment was submitted to model studies, including esterification with a bulky alcohol at the C1 position and Stille coupling with vinyl iodide at the C13 position. The reactivity of the C1 position was affected by the neighboring C2-protective group. When the C2 hydroxy group was protected as a TBS ether, the C1 carboxylic acid did not undergo esterification with a bulky secondary alcohol, whereas the p -methoxybenzylidene N , O -acetal afforded a 2,4-dimethyl-3-pentyl ester. Stille coupling of the C1–C13 segment with 1-iodohept-1-ene gave the southern part of the poecillastrin C macrolactam attached to simplified eastern and western parts. [ABSTRACT FROM AUTHOR]

Ni‐catalyzed activation of C(sp2)−H bond remains an elusive challenge. Herein, we realized a Ni‐catalyzed selective activation of C(sp2)−H bond of formamides, which underwent addition reaction with internal alkynes to provide α,β‐unsaturated amide compounds in high yields. The protocol was featured by the cheap and nontoxic catalyst system. Preliminary mechanistic studies shed light on the reaction pathways. [ABSTRACT FROM AUTHOR]

As part of a series of studies of hydrogen‐atom transfer or tautomerization reactions of imidic acid–amide species, H─O═C─N─⇌O═C─N─H${\rm H\bond O\dbond C\bond N\bond} \rightleftharpoons {\rm O\dbond C\bond N\bond H}$, we report the rate constants for a set of 24 five‐membered cyclic compounds at low, 50–300 K, and high, 500–1500 K, temperatures. These rate constants are for both the high temperature direct reaction and for that mediated by an additional water molecule which facilitates the hydrogen transfer reaction at low temperatures. In the latter case we show that the rate of reaction from a pre‐reaction complex can be rapid at temperatures down to 50 K on a 1 ms timescale and is dominated by quantum mechanical effects as evaluated by small‐curvature and quantised‐reaction‐states tunnelling. In addition, we present thermochemical data such as enthalpies of formation, entropies, isobaric heat capacities and enthalpy functions for these largely unknown species which span a range of compounds from pyrolidinone to oxo‐tetrazoles. [ABSTRACT FROM AUTHOR]

An efficient method for the oxidative transformation of thioamides and thioketones to their oxygen analogues with singlet oxygen is reported. Singlet oxygen was produced in situ from the fragmentation of the trans-5-hydroperoxy-3,5-dimethyl-1,2-dioxolane-3-yl ethaneperoxate in the presence of KOH, and it has been explored as an effective oxidant for oxidative desulfurization of thioamides and thioketones. This protocol provides amides and ketones in excellent yields (80–90%) at room temperature under mild conditions. The thioamides reacted very well with this reagent system. The conjugation of neighboring NH and C=S groups appears to enhance yields for thioamides. Further investigation showed that this reagent system is also an efficient system for deprotection of thionoesters to esters. [ABSTRACT FROM AUTHOR]

An efficient transamidation process has been described under solvent-less conditions. The transformation has been accomplished by employing NH2OH⦁HCl as a reagent and amines as substrates. The developed method is achieved in the absence of metals and hazardous reagents. A series of amines were explored to obtain the N-formylation and N-acylation reactions with excellent yields (81-96%) of products. The DFT analysis was also performed, which provides a clear understanding of the described N-formylation process. The postulated mechanism is well supported by the control experiments. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of N -alkoxy lactams and oximinolactones, involving the selective N -cyclization and O -cyclization of unsaturated N -alkoxy amides, is presented. This approach features mild reaction conditions and no requirement for transition-metal catalysts. The protocol demonstrates a wide range of applicability in 5- exo - trig and 6- exo - trig cyclization, accommodating chloro, bromo, and iodo electrophiles. The N -cyclization process can be achieved in the presence of strong lithium base such as LiHMDS or n -BuLi, while the O -cyclization occurs spontaneously without the addition of any base. Mechanistic studies reveal the N -cyclization reactions proceed through cyclic lithium intermediates, as confirmed by FT-IR studies and control experiments, which contribute to the N -selectivity. The current methodology was successfully used in synthesis of natural product (E / Z) des -hydroxy triticone A and B. [ABSTRACT FROM AUTHOR]

Biocatalytic hydroamination of alkenes is an efficient and selective method to synthesize natural and unnatural amino acids. Phenylalanine ammonia‐lyases (PALs) have been previously engineered to access a range of substituted phenylalanines and heteroarylalanines, but their substrate scope remains limited, typically including only arylacrylic acids. Moreover, the enantioselectivity in the hydroamination of electron‐deficient substrates is often poor. Here, we report the structure‐based engineering of PAL from Planctomyces brasiliensis (PbPAL), enabling preparative‐scale enantioselective hydroaminations of previously inaccessible yet synthetically useful substrates, such as amide‐ and ester‐containing fumaric acid derivatives. Through the elucidation of cryo‐electron microscopy (cryo‐EM) PbPAL structure and screening of the structure‐based mutagenesis library, we identified the key active site residue L205 as pivotal for dramatically enhancing the enantioselectivity of hydroamination reactions involving electron‐deficient substrates. Our engineered PALs demonstrated exclusive α‐regioselectivity, high enantioselectivity, and broad substrate scope. The potential utility of the developed biocatalysts was further demonstrated by a preparative‐scale hydroamination yielding tert‐butyl protected l‐aspartic acid, widely used as intermediate in peptide solid‐phase synthesis. [ABSTRACT FROM AUTHOR]

Biocatalytic hydroamination of alkenes is an efficient and selective method to synthesize natural and unnatural amino acids. Phenylalanine ammonia‐lyases (PALs) have been previously engineered to access a range of substituted phenylalanines and heteroarylalanines, but their substrate scope remains limited, typically including only arylacrylic acids. Moreover, the enantioselectivity in the hydroamination of electron‐deficient substrates is often poor. Here, we report the structure‐based engineering of PAL from Planctomyces brasiliensis (PbPAL), enabling preparative‐scale enantioselective hydroaminations of previously inaccessible yet synthetically useful substrates, such as amide‐ and ester‐containing fumaric acid derivatives. Through the elucidation of cryo‐electron microscopy (cryo‐EM) PbPAL structure and screening of the structure‐based mutagenesis library, we identified the key active site residue L205 as pivotal for dramatically enhancing the enantioselectivity of hydroamination reactions involving electron‐deficient substrates. Our engineered PALs demonstrated exclusive α‐regioselectivity, high enantioselectivity, and broad substrate scope. The potential utility of the developed biocatalysts was further demonstrated by a preparative‐scale hydroamination yielding tert‐butyl protected l‐aspartic acid, widely used as intermediate in peptide solid‐phase synthesis. [ABSTRACT FROM AUTHOR]

Lanthanide metal–organic frameworks (Ln-MOFs) have unique advantages in sensing due to their excellent optical properties. In this study, we synthesized a dicarboxylic acid ligand with amide groups and successfully synthesized a novel two-dimensional (2D) MOF with the molecular formula C42H31EuN4O10 (Eu-MOF) by a solvothermal method. Single-crystal X-ray diffraction showed that amide groups are exposed on the outside of the two-dimensional coordination layer, with the possibility of recognizing specific molecules through hydrogen bonding interactions. The ligand's "antenna effect" enables Eu-MOF to emit a strong luminescence characterized by the "f–f" transition. Further studies have revealed that Eu-MOF could be used as a bifunctional fluorescent probe for the selective detection of benzaldehyde and Fe3+. The sensing mechanism has been analyzed in detail through powder X-ray diffraction (PXRD) analysis, UV-vis spectroscopy, fluorescence lifetime measurement, and density functional (DFT) theory calculation. This design and research can provide a reference for subsequent related work. [ABSTRACT FROM AUTHOR]

Electrocatalytic C−N couplings are promising alternatives to construct C−N bonds and to synthesize vital chemicals, including amine, amide, amino acid, oxime, imine, and nitrile, under ambient conditions. In recent years, the electrocatalytic C−N coupling has attracted a wide range of research interest and has achieved considerable developments. Here, the electrocatalytic C−N coupling is systematically reviewed aiming at reductive cathode and oxidative anode. In the cathodic part, the electrocatalytic coupling reaction systems, the corresponding design principles of electrocatalysts for different reaction systems, the mechanism studies from experimental and theoretical aspects, and the application‐oriented electrocatalytic devices for electrocatalytic C−N couplings are summarized. Anodic C−N coupling offers a potential approach to replace the conventional energy‐demand synthesis protocols, and is an indispensable part of the green and controllable construction of unsaturated C = N and C≡N bonds. According to the principle that electron transfer is the crucial point in anodic C−N coupling, the anodic coupling reactions are sorted out based on the direct and the indirect C−N coupling paths, respectively. Finally, the challenges and outlooks in this field are proposed. Electrocatalytic C−N coupling is an appealing research topic in electrochemistry and possesses infinite possibilities in the future. [ABSTRACT FROM AUTHOR]

We herein report that the highly hydrophobic ether 4‐MeTHP constitutes a promising resource for the development of sustainable synthetic methodologies grounded on the use of organometallic reagents. The beneficial effects of 4‐MeTHP as reaction medium are illustrated in the organolithium‐promoted anionic ortho‐Fries rearrangement of 1,1'‐bi‐2‐naphthol (BINOL)‐based carbamates under bench‐type conditions. The use of 4‐MeTHP induces a remarkable and unexpected stability of the organolithiums species, enabling the efficient preparation of chiral (bis)carboxamide catalysts. Furthermore, superior performances of 4‐MeTHP than other environmentally responsible solvents are observed using the synthesized BINOL catalysts in the asymmetric addition of organozinc reagents to aldehydes. Spectroscopic studies in solution suggest that 4‐MeTHP plays a key role in these reactions by inducing the preferential formation of a reactive monomeric dinuclear complex. This methodology allows for the asymmetric assembly of enantioenriched secondary alcohols in good yields and high stereoselectivity, working at 0 °C and under air. [ABSTRACT FROM AUTHOR]

Herein, we have demonstrated a palladium-catalyzed regioselective allylation of unactivated alkenes with vinylcyclopropanes assisted by weak-coordinating native amides. The reaction exhibits wide substrate scope and excellent β-selectivity. Substrate diversification was performed to demonstrate the synthetic utility of the reaction. Mechanistic investigations were carried out to provide an insight into the reaction mechanism. [ABSTRACT FROM AUTHOR]

Deprotection of amides is a virtually universal transformation in organic synthesis, often employing traditional active reductants such as SmI2, hydrosilanes, hydroboranes or H2 under high-pressure. Herein, we describe a green and sustainable electrocatalytic hydrolysis of amides utilizing water as the hydrogen source, thereby ideally avoiding the use of high-pressure and flammable hydrogen gas or other toxic and costly hydrogen donors. Our methodology utilized green electrons as reductants, facilitating highly selective and efficient electrocatalytic C–N hydrolysis of amides. This environmentally friendly electrochemical approach can also be successfully applied to the C–N hydrolysis of carbamates, formamides, and thioamides. Furthermore, this method extends to the dissociation of O–N and N–N bonds, exhibiting a wide scope and high functional group tolerance. Preliminary mechanistic studies support a proposed mechanism involving the electroreductive conversion of the carbonyl group into a hemiaminal intermediate, which subsequently collapses to yield free amines. [ABSTRACT FROM AUTHOR]

Organic molecules with light‐modifiable reactivity are important in many fields because they can serve as the "switch" for light to trigger chemical processes. Herein, we disclose a new type of stable non‐twisted amides, the reactivity of which can be turned on by light as acyl transfer reagents. Upon photo‐activation, these amides react with various nucleophiles including amines, phenols, hydroxide, thiols, boronic acids, and alkynes either under metal‐free or metal‐catalysis conditions. This reactivity hinges on the design and synthesis of a photo‐activatable reagent (7‐nitro‐5,6‐dihydrophenanthridine), which undergoes self‐aromatization enabled by an internal oxidant under light. This masked acyl donor group is anticipated to be useful in scenarios where light is preferred to trigger a chemical process. [ABSTRACT FROM AUTHOR]

The macrocyclic tumonolide (1) with enamide functionality and the linear tumonolide aldehyde (2) are new interconverting natural products from a marine cyanobacterium with a peptide‐polyketide skeleton, representing a hybrid of apratoxins and palmyrolides or laingolides. The planar structures were established by NMR and mass spectrometry. The relative configuration of the stereogenically‐rich apratoxin‐like polyketide portion was determined using J‐based configuration analysis. The absolute configuration of tumonolide (1) was determined by chiral analysis of the amino acid units and computational methods, followed by NMR chemical shift and ECD spectrum prediction, indicating all‐R configuration for the polyketide portion, as in palmyrolide A and contrary to the all‐S configuration in apratoxins. Functional screening against a panel of 168 GPCR targets revealed tumonolide (1) as a selective antagonist of TACR2 with an IC50 of 7.0 μM, closely correlating with binding affinity. Molecular docking studies established the binding mode and rationalized the selectivity for TACR2 over TACR1 and TACR3. RNA sequencing upon treatment of HCT116 colorectal cancer cells demonstrated activation of the pulmonary fibrosis idiopathic signaling pathway and the insulin secretion signaling pathway at 20 μM, indicating its potential to modulate these pathways. [ABSTRACT FROM AUTHOR]

Gold allenylidene species have been seldom exploited as reactive intermediates in synthetically versatile catalytic reactions. By employing alkynylbenziodoxoles as the substrates and bifunctional WangPhos as the metal ligand, this work demonstrated ready catalytic access to these intermediates of general substitution patterns and their electrophilic reactivities at the γ‐carbon center with a diverse range of nucleophiles. The reaction is driven by the reductive decomposition of the benziodoxole moiety and achieves the replacement of a propargylic proton with an N/O/C‐based nucleophile, hence realizing reactivity umpolung. Corroborated by Density Functional Theory (DFT) calculations, the reaction mechanism involves a mild propargylic deprotonation. In contrast to prior works employing a tertiary amine functionality, a weakly BrØnsted‐basic amide group in WangPhos is surprisingly effective in deprotonation at the propargylic position under a gold‐ligand cooperation regime. [ABSTRACT FROM AUTHOR]

Gold allenylidene species have been seldom exploited as reactive intermediates in synthetically versatile catalytic reactions. By employing alkynylbenziodoxoles as the substrates and bifunctional WangPhos as the metal ligand, this work demonstrated ready catalytic access to these intermediates of general substitution patterns and their electrophilic reactivities at the γ‐carbon center with a diverse range of nucleophiles. The reaction is driven by the reductive decomposition of the benziodoxole moiety and achieves the replacement of a propargylic proton with an N/O/C‐based nucleophile, hence realizing reactivity umpolung. Corroborated by Density Functional Theory (DFT) calculations, the reaction mechanism involves a mild propargylic deprotonation. In contrast to prior works employing a tertiary amine functionality, a weakly BrØnsted‐basic amide group in WangPhos is surprisingly effective in deprotonation at the propargylic position under a gold‐ligand cooperation regime. [ABSTRACT FROM AUTHOR]

Copper‐catalyzed and visible‐light catalytic difluoroalkylation reactions of N‐cyanamide alkenes have been developed. Various α‐bromodifluoromethyl substituted esters, amides and heterocycles were employed as the CF2 source. Both protocols are characterized by medium to high yields, good functional group compatibility, and applicable to gram‐scale synthesis. Comparable studies of copper catalysis and photoredox catalysis demonstrate minimal differences between the two protocols. Preliminary mechanism suggest that both transformations involve tandem radical cyclization process. [ABSTRACT FROM AUTHOR]

A simple protocol for amide bond construction using β‐keto sulfonyl fluorides (BKSFs) as the acyl surrogates has been achieved. The reaction of BKSFs with a range of amines could be performed in presence of N‐bromosuccinimide (NBS), affording various amides with diverse functionalities. Preliminary mechanistic studies revealed that the dibromo‐substituted sulfonyl fluorides could be the key intermediate in this amidation process. [ABSTRACT FROM AUTHOR]

Herein, we report a solely ligand centered redox controlled protocol, utilizing a bench stable zinc compound, for the efficient coupling of o-amino amides/esters with nitriles to afford diverse quinazolinone scaffolds and their synthetic utility was showcased via post-modification to access therapeutically relevant compounds. Importantly, mechanistic probes established the reaction pathway that proceeds via aminyl radical. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of acyl hydrazides and hydrazones from activated amides, which are nitrogen-containing compounds found in pharmaceutical and agricultural compounds. The traditional method for synthesizing acyl hydrazides has limitations, but recent advancements in carbon-nitrogen bond activation reactions have opened up new possibilities. The article provides a comprehensive account of the results and methodologies for synthesizing these compounds, including the synthesis and characterization of various benzohydrazide compounds. The document also includes specific details for the synthesis and characterization of one compound, (E)-N'-(4-methylbenzylidene)benzohydrazide. The document provides experimental results, including yields, melting points, and spectroscopic data, and acknowledges the Korea Basic Science Institute for providing additional data. [Extracted from the article]

A method for the radiosynthesis of 18F-labelled aryl trifluoromethyl ketones starting from widely available Weinreb amides using [18F]fluoroform is presented. The method uses potassium hexamethyldisilazane as base and delivers products in high molar activity (up to 24 GBq μmol−1) and excellent radiochemical conversions. The applicability for PET tracer synthesis is demonstrated by the radiosynthesis of ten (hetero)aryl trifluoromethylketones, bearing electron-withdrawing and -donating substituents including a derivative of bioactive probenecid. [ABSTRACT FROM AUTHOR]