Oxidative Cyclization Research Articles

Palladium(0) π-Lewis Base Catalysis: Concept and Development.

The development of a new catalytic strategy plays a vital role in modern organic chemistry since it permits bond formation in an unprecedented and more efficient manner. Although the application of preformed metal complexes as π-base-activated reagents have enabled diverse transformations elegantly, the concept and strategy by directly utilizing transition metals as efficient π-Lewis base catalysts remain underdeveloped, especially in the field of asymmetric catalysis. Here, we outline our perspective on the discovery of palladium(0) as an efficient π-Lewis base catalyst, which is capable of increasing the highest occupied molecular orbital (HOMO) energy of both electron-neutral and electron-deficient 1,3-dienes and 1,3-enynes upon flexible η2-complexes formed in situ and resultant π-backdonation. Thus, fruitful carbon-carbon-forming reactions with diverse electrophiles can be achieved enantioselectively in a vinylogous addition pattern, which is conceptually different from the classical oxidative cyclization mechanism. Emphasis will be given to the concept and mechanism elucidation, catalytic features, and reaction design together with perspective on the further development of this emerging field.

Oxidation behavior of Ti2AlC MAX phase-based coating on a γ-TiAl alloy TiAl48-2-2 produced by DC magnetron sputtering

The application of intermetallic γ-TiAl-based alloys is limited by the deterioration in strength and creep resistance as well as reduction in oxidation resistance above 750 °C. The deposition of protective coatings is a promising opportunity to enhance the oxidation resistance or the lifetime with regard to the sustainability by several orders of magnitude. Moreover, additive manufacturing processes could enable the production of components with more complex geometries in the future. Thus, designs of γ-TiAl turbine blades with internal cooling systems could be feasible in the near future. In this context, the deposition of thermal barrier coatings and, therefore, oxidation protective bond coatings became important. MAX phases are of increasing interest as coating materials for high temperature applications due to their unique combination of metallic and ceramic properties. Especially the alumina forming MAX phases such as Cr2AlC, Ti2AlC or Ti2AlN are promising coating materials.In the present work a Ti2AlC MAX-phase based coating was deposited by DC magnetron sputtering. Using three pure elemental target materials - Ti, Al and C and a two-fold rotation, a homogenous all-around coating was applied on the γ-TiAl alloy TiAl48-2-2 with a coating thickness of 10 μm. After the deposition process the stochiometric Ti2AlC coating was X-ray amorphous, therefore a post-heat treatment at 800 °C for 1 h was performed to achieve the desired hexagonal phase. Finally, the MAX-phase coated TiAl48-2-2 alloy was subjected to a cyclic oxidation test at 850 °C in laboratory air. The Ti2AlC MAX-phase coated TiAl48-2-2 alloy exhibits an excellent oxidation behavior, due to the formation of a thermally grown alumina top layer with the desired hexagonal Ti2AlC MAX-phase below. Extensive TEM analyses also showed the dependence of Al2O3 formation on post-heat treatment. θ-Al2O3 with a lower protective effect and the concomitant formation of TiN under the TGO was observed with post-heat treatment in Ar, while post-heat treatment in air lead to the formation of a protective α-Al2O3 layer.

Unraveling the atomic interdiffusion mechanism of NiFe2O4 oxygen carriers during chemical looping CO2 conversion

AbstractBy employing metal oxides as oxygen carriers, chemical looping demonstrates its effectiveness in transferring oxygen between reduction and oxidation environments to partially oxidize fuels into syngas and convert CO2 into CO. Generally, NiFe2O4 oxygen carriers have demonstrated remarkable efficiency in chemical looping CO2 conversion. Nevertheless, the intricate process of atomic migration and evolution within the internal structure of bimetallic oxygen carriers during continuous high‐temperature redox cycling remains unclear. Consequently, the lack of a fundamental understanding of the complex ionic migration and oxygen transfer associated with energy conversion processes hampers the design of high‐performance oxygen carriers. Thus, in this study, we employed in situ characterization techniques and theoretical calculations to investigate the ion migration behavior and structural evolution in the bulk of NiFe2O4 oxygen carriers during H2 reduction and CO2/lab air oxidation cycles. We discovered that during the H2 reduction step, lattice oxygen rapidly migrates to vacancy layers to replenish consumed active oxygen species, while Ni leaches from the material and migrates to the surface. During the CO2 splitting step, Ni migrates toward the core of the bimetallic oxygen carrier, forming Fe–Ni alloys. During the air oxidation step, Fe–Ni migrates outward, creating a hollow structure owing to the Kirkendall effect triggered by the swift transfer of lattice oxygen. The metal atom migration paths depend on the oxygen transfer rates. These discoveries highlight the significance of regulating the release–recovery rate of lattice oxygen to uphold the structures and reactivity of oxygen carriers. This work offers a comprehensive understanding of the oxidation/reduction‐driven atomic interdiffusion behavior of bimetallic oxygen carriers.

Electrochemical Lactonization Enabled by Unusual Shono-Type Oxidation from Functionalized Benzoic Acids.

A novel method for electrochemical lactonization via C(sp3)-H functionalization was developed. This metal- and oxidant-free strategy enabled the efficient synthesis of various lactones. Gram-scale reaction and derivatization of the lactone product demonstrated the synthetic utility of this methodology. Mechanistic studies using control experiments and CV curves elucidated the proposed intramolecular HAT and the oxidative cyclization pathway. An unusual Shono-type oxidation was realized through this electrochemical approach, proceeding without a traditional nucleophilic addition process.

Microwave-Accelerated Synthesis of Flavanones through Oxidative Cyclization of 2'-Hydroxychalcones Using Acetic Acid as a Sole Catalyst

Under microwave irradiation conditions, 2'-hydroxy chalcones 1a-c underwent AcOH-mediated cyclization in an oxa-Michael addition manner to afford flavanones 2a-c in acceptable yields (up to 82%). These reactions proceeded in a shorter reaction time (~ 30 min) through microwave activation; otherwise, the reaction would take several days and even weeks, if a conventional heating process was employed. For example, cyclization of (E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (1a) has required 4 days of stirring with AcOH (0.25 M), under conventional heating at 100 °C, to produce 2-phenylchroman-4-one (2a), in 75% yield; while under microwave conditions, the reaction has yielded 82% of compound 2a, after 30 min. Thus obtained products 2a-c were fully characterized by recording of melting point together with UV, 1H NMR, and 13C NMR spectra.

Total Synthesis of Laurane and Guaiane Sesquiterpenoids via Oxidative Nazarov Reaction

Comprehensive SummaryAs one of the most common structural motifs in natural products, cyclopentenones usually can be fabricated by Nazarov cyclization using divinyl ketones or functionalized tertiary divinyl carbinols (TDCs) as substrates. However, straightforward method for transforming unfunctionalized TDCs to their corresponding cyclopentenones is currently lacking. Herein, we wish to report the total syntheses of four structurally distinct terpenoids, namely laurane‐type marine sesquiterpenoids isolaurene, debromoaplysin and aplysin, and guaiane sesquiterpenoid guaiadienone A, all using a novel synthetic method, named oxidative Nazarov cyclization, as the key step. This work demonstrated our robust method is suitable for synthesizing various highly substituted cyclopentenones.

A neuron–glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis

Sleep is thought to be restorative to brain energy homeostasis, but it is not clear how this is achieved. We show here that Drosophila glia exhibit a daily cycle of glial mitochondrial oxidation and lipid accumulation that is dependent on prior wake and requires the Drosophila APOE orthologs NLaz and GLaz, which mediate neuron–glia lipid transfer. In turn, a full night of sleep is required for glial lipid clearance, mitochondrial oxidative recovery and maximal neuronal mitophagy. Knockdown of neuronal NLaz causes oxidative stress to accumulate in neurons, and the neuronal mitochondrial integrity protein, Drp1, is required for daily glial lipid accumulation. These data suggest that neurons avoid accumulation of oxidative mitochondrial damage during wake by using mitophagy and passing damage to glia in the form of lipids. We propose that a mitochondrial lipid metabolic cycle between neurons and glia reflects a fundamental function of sleep relevant for brain energy homeostasis.

Synthesis of Chiral Sulfoxides by A Cyclic Oxidation-Reduction Multi-Enzymatic Cascade Biocatalysis.

Optically pure sulfoxides are valuable organosulfur compounds extensively employed in medicinal and organic synthesis. In this study, we present a biocatalytic oxidation-reduction cascade system designed for the preparation of enantiopure sulfoxides. The system involves the cooperation of a low-enantioselective chimeric oxidase SMO (styrene monooxygenase) with a high-enantioselective reductase MsrA (methionine sulfoxide reductase A), facilitating "non-selective oxidation and selective reduction" cycles for prochiral sulfide oxidation. The regeneration of requisite cofactors for MsrA and SMO was achieved via a cascade catalysis process involving three auxiliary enzymes, sustained by cost-effective D-glucose. Under the optimal reaction conditions, a series of heteroaryl alkyl, aryl alkyl and dialkyl sulfoxides in R configuration were synthesized through this "one-pot, one step" cascade reaction. The obtained compounds exhibited high yields of >90 % and demonstrated enantiomeric excess (ee) values exceeding 90 %. This study represents an unconventional and efficient biocatalytic way in utilizing the low-enantioselective oxidase for the synthesis of enantiopure sulfoxides.

Targeting the NF-κB p65/Bcl-2 signaling pathway in hepatic cellular carcinoma using radiation assisted synthesis of zinc nanoparticles coated with naturally isolated gallic acid

PurposeOral diethylnitrosamine (DEN) is a known hepatocarcinogen that damages the liver and causes cancer. DEN damages the liver through reactive oxygen species-mediated inflammation and biological process regulation. Materials and methodsGallic acid-coated zinc oxide nanoparticles (Zn-GANPs) were made from zinc oxide (ZnO) synthesized by irradiation dose of 50 kGy utilizing a Co-60 γ-ray source chamber with a dose rate of 0.83 kGy/h and gallic acid from pomegranate peel. UV–visible (UV) spectrophotometry verified Zn-GANP synthesis. TEM, DLS, and FTIR were utilized to investigate ZnO-NPs' characteristics.Rats were orally exposed to DEN for 8 weeks at 20 mg/kg five times per week, followed by intraperitoneal injection of Zn-GANPs at 20 mg/kg for 5 weeks. Using oxidative stress, anti-inflammatory, liver function, histologic, apoptotic, and cell cycle parameters for evaluating Zn-GANPs treatment. ResultsDEN exposure elevated inflammatory markers (AFP and NF-κB p65), transaminases (AST, ALT), γ-GT, globulin, and total bilirubin, with reduced protein and albumin levels. It also increased MDA levels, oxidative liver cell damage, and Bcl-2, while decreasing caspase-3 and antioxidants like GSH, and CAT. Zn-GANPs significantly mitigated these effects and lowered lipid peroxidation, AST, ALT, and γ-GT levels, significantly increased CAT and GSH levels (p<0.05). Zn-GANPs caused S and G2/M cell cycle arrest and G0/G1 apoptosis. These results were associated with higher caspase-3 levels and lower Bcl-2 and TGF-β1 levels. Zn-GANPs enhance and restore the histology and ultrastructure of the liver in DEN-induced rats. ConclusionThe data imply that Zn-GANPs may prevent and treat DEN-induced liver damage and carcinogenesis.

Synthesis of 1,1'-Bicarbazoles by Sequential Iron(III)- and Palladium(II)-Catalyzed Oxidative Coupling Reactions.

The iron(III)-catalyzed oxidative coupling of diarylamines to 2,2'-bis(arylamino)-1,1'-biaryls and subsequent twofold palladium(II)-catalyzed oxidative cyclization provide a convergent synthetic route to 1,1'-bicarbazoles. Screening a range of different palladium(II) salts led to palladium(II) acetate, pivalate, and hexafluoroacetylacetonate as the most efficient catalysts. Remarkably, the twofold palladium(II)-catalyzed oxidative cyclization can also be performed under argon. The mechanism for the oxidative cyclization under an inert gas presumably involves regeneration of the catalytically active palladium(II) species by oxidative addition of pivalic acid.

Total Synthesis of Daphniphyllum Alkaloids: (+)-Daphlongamine E, (+)-Calyciphylline R, and (–)-10-Deoxydaphnipaxianine A

AbstractHere, we wish to describe our detailed efforts in the total synthesis of three calyciphylline A-type alkaloids, namely (+)-daphlongamine E, (+)-calyciphylline R, and (–)-10-deoxydaphnipaxianine A. Important steps in our approach include a Pt-catalyzed nitrile hydration, a Babler–Dauben rearrangement, a novel selective amide reduction tactic, and an oxidative Nazarov cyclization via an unfunctionalized tertiary divinyl carbinol (TDC).

Redox and melting characteristics of Mn-based ores for high-temperature thermochemical energy storage

Redox and melting characteristics of Mn-based ores were investigated to test their potential use in thermochemical energy storage (TCES). Two Mn-based materials (FJ and LY) were natural ores with the Mn content higher than 35 wt%, and one Mn-based material was prepared by adding an MgO–kaolin inert support into LY ores to increase its melting temperature. Cyclic reduction and oxidation reactivity of these Mn-based materials was studied via thermogravimetric analysis (TGA), and the melting behaviors of these materials were investigated by using a melting test setup with an optical camera–image system. It was found that the oxygen capacity of the FJ Mn ore can approach ∼1.50 wt%, while the LY Mn ore had only 0.42 wt%–0.69 wt% oxygen capacity The deformation temperature of the FJ Mn ore is higher than that of the LY Mn ore, and the melting temperatures of the LY Mn ore can be significantly improved with the addition of an MgO–kaolin inert support, while the reactivity is decreased due to the addition of the MgO–kaolin inert material. This study proves that manganese ores with high oxygen capacity and deformation temperature have potential as TCES materials. For some manganese ores with low deformation temperatures, it is necessary to improve their melting temperatures and ensure oxygen capacity for high-temperature TCES applications.

Prevalence of inherited metabolic disorders among newborns in Zhuzhou, a southern city in China.

Background and aims: Defective enzymes, cofactors, or transporters of metabolic pathways cause inherited metabolic disorders (IMDs), a group of genetic disorders. Several IMDs have serious consequences for the affected neonates. Newborn screening for IMDs is conducted by measuring specific metabolites between 3 and 7days of life. Herein, we analyzed the incidence, spectrum, and genetic characteristics of IMDs in newborns in the Zhuzhou area. Methods: Tandem mass spectrometry was conducted on 90,829 newborns who were admitted to the Women and Children Healthcare Hospital of Zhuzhou and requested for screening for IMDs. These newborns were subsequently subjected to next-generation sequencing and further validated using Sanger sequencing. Results: 30 IMDs cases were found in 90,829 cases of newborns screened for IMDs, and the overall incidence was 1/3,027. The incidence of amino acid, organic acid, fatty acid oxidation and urea cycle disorders were 1/8,257, 1/18,165, 1/7,569, and 1/45,414, respectively. Additionally, 9 cases of maternal IMDs were found in our study, and unreported gene mutations of 3 cases IMDs were identified. Conclusion: Our data indicated that IMDs are never uncommon in zhuzhou, meanwhile, we also found that primary carnitine deficiency was the only disorder of fatty acid oxidation in Zhuzhou, and the incidence (1/7,569) was higher than the national level, organic acid metabolic diseases are mostly inherited. Therefore, our study has clarified the disease spectrum and genetic backgrounds, contributing to the treatment and prenatal genetic counseling of these disorders in this region.

Model-guided metabolic rewiring to bypass pyruvate oxidation for pyruvate derivative synthesis by minimizing carbon loss.

Engineering microbial hosts to synthesize pyruvate derivatives depends on blocking pyruvate oxidation, thereby causing severe growth defects in aerobic glucose-based bioprocesses. To decouple pyruvate metabolism from cell growth to improve pyruvate availability, a genome-scale metabolic model combined with constraint-based flux balance analysis, geometric flux balance analysis, and flux variable analysis was used to identify genetic targets for strain design. Using translation elements from a ~3,000 cistronic library to modulate fxpK expression in a bicistronic cassette, a bifido shunt pathway was introduced to generate three molecules of non-pyruvate-derived acetyl-CoA from one molecule of glucose, bypassing pyruvate oxidation and carbon dioxide generation. The dynamic control of flux distribution by T7 RNAP-mediated synthetic small RNA decoupled pyruvate catabolism from cell growth. Adaptive laboratory evolution and multi-omics analysis revealed that a mutated isocitrate dehydrogenase functioned as a metabolic switch to activate the glyoxylate shunt as the only C4 anaplerotic pathway to generate malate from two molecules of acetyl-CoA input and bypass two decarboxylation reactions in the tricarboxylic acid cycle. A chassis strain for pyruvate derivative synthesis was constructed to reduce carbon loss by using the glyoxylate shunt as the only C4 anaplerotic pathway and the bifido shunt as a non-pyruvate-derived acetyl-CoA synthetic pathway and produced 22.46, 27.62, and 6.28 g/L of l-leucine, l-alanine, and l-valine by a controlled small RNA switch, respectively. Our study establishes a novel metabolic pattern of glucose-grown bacteria to minimize carbon loss under aerobic conditions and provides valuable insights into cell design for manufacturing pyruvate-derived products.IMPORTANCEBio-manufacturing from biomass-derived carbon sources using microbes as a cell factory provides an eco-friendly alternative to petrochemical-based processes. Pyruvate serves as a crucial building block for the biosynthesis of industrial chemicals; however, it is different to improve pyruvate availability in vivo due to the coupling of pyruvate-derived acetyl-CoA with microbial growth and energy metabolism via the oxidative tricarboxylic acid cycle. A genome-scale metabolic model combined with three algorithm analyses was used for strain design. Carbon metabolism was reprogrammed using two genetic control tools to fine-tune gene expression. Adaptive laboratory evolution and multi-omics analysis screened the growth-related regulatory targets beyond rational design. A novel metabolic pattern of glucose-grown bacteria is established to maintain growth fitness and minimize carbon loss under aerobic conditions for the synthesis of pyruvate-derived products. This study provides valuable insights into the design of a microbial cell factory for synthetic biology to produce industrial bio-products of interest.

Synthesis of Indazoles via N-N Bond-Forming Oxidative Cyclization from 2-Aminomethyl-phenylamines.

Herein we report a method for the synthesis of indazoles from readily available 2-aminomethyl-phenylamines via N-N bond-forming oxidative cyclization. Inspired by indazole formation initially observed as a side product by N. Coskun et al. we developed a robust protocol to access indazoles in all three tautomeric forms. The method selectively gives access to various 2-substituted 2H-indazoles which are frequently used in drug design, and we also demonstrated its applicability to less studied 3H-indazoles.

Sequential Oxidation/Cyclization of Readily Available Imine Linkages to Access Benzoxazole‐Linked Covalent Organic Frameworks

AbstractBenzoxazole‐linked covalent organic frameworks (BO−COFs), despite their exceptional chemical stability, are still in their infancy. This is primarily because the current prevalent methods require the use of special ortho‐hydroxyl‐substituted aromatic amines as monomers. Herein, we report an innovative strategy to access BO−COFs directly from imine‐linked COFs (Im−COFs) without pre‐embedded OH groups, using a two‐step sequential oxidation/cyclization process. The two‐step process included the oxidation of Im−COFs into amide‐linked COFs, followed by a copper‐catalyzed oxidative cyclization. Five representative BO−COFs were synthesized with retained crystallinity and high oxidization efficiency, offering the potential to convert a significant portion of Im−COFs into BO−COFs. The structural advantages of the newly designed BO−COFs were demonstrated through their application to photocatalytic organic transformations.

Sequential Oxidation/Cyclization of Readily Available Imine Linkages to Access Benzoxazole-Linked Covalent Organic Frameworks.

Benzoxazole-linked covalent organic frameworks (BO-COFs), despite their exceptional chemical stability, are still in their infancy. This is primarily because the current prevalent methods require the use of special ortho-hydroxyl-substituted aromatic amines as monomers. Herein, we report an innovative strategy to access BO-COFs directly from imine-linked COFs (Im-COFs) without pre-embedded OH groups, using a two-step sequential oxidation/cyclization process. The two-step process included the oxidation of Im-COFs into amide-linked COFs, followed by a copper-catalyzed oxidative cyclization. Five representative BO-COFs were synthesized with retained crystallinity and high oxidization efficiency, offering the potential to convert a significant portion of Im-COFs into BO-COFs. The structural advantages of the newly designed BO-COFs were demonstrated through their application to photocatalytic organic transformations.

Impact of Pt/Al ratios on the cyclic oxidation and TCP precipitation of β-(Ni, Pt)Al coated superalloy at 1150 °C

The cyclic oxidation and topologically close-packed (TCP) phase precipitation behaviors of β-(Ni, Pt)Al coatings with different Pt/Al ratios at 1150 °C were investigated. In the initial oxidation stage, coatings with different Pt/Al ratios exhibited comparable high-temperature oxidation resistance, likely due to a similar level of Al absorption. Subsequently, oxide spallation was common for coatings with lower Pt/Al ratios due to the formation of fine-grained alumina and a “sandwich” structure (a multilayer porous structure) oxide scale. For coatings with higher Pt/Al ratios, severe rumpling occurred, and numerous cracks formed in the oxide scale. However, sufficient Al concentration in the outer zone and the improved deformation tolerance of the oxide scale enhanced the spallation resistance of the thermally grown oxide (TGO). Furthermore, a higher Pt/Al ratio promotes uphill diffusion of Al, which reduces its migration into the substrate, thereby diminishing TCP precipitation. Coatings with the same Pt/Al ratios but higher Pt and Al contents further reduced TCP precipitation after oxidation. This improvement is attributed to the initially lower Al concentration in these coatings' secondary reaction zone (SRZ) and their greater thickness.

Paradoxical systemic toxicity by inhaled paraquat poisoning: A case report

Rationale: Multi-organ failure is a symptom of paraquat poisoning, resulting in high mortality and morbidity rates. Though paraquat is widely available, poisoning through inhalation is rare. Patient's Concern: A 37-year-old male reported to the emergency department with complaints of vomiting after an alleged history of inhalation of paraquat while at work. Diagnosis: Paraquat poisoning. Interventions: Supportive management along with multiple sessions of hemodialysis. Outcomes: Renal complications caused by paraquat were improved after multiple sessions of hemodialysis. However, the patient developed respiratory complications and later due to persistent hypoxemia and non-responsive to supportive therapy, he succumbed to his illness. Lessons: Acute kidney injury is a complication of paraquat poisoning. However, kidney involvement with the inhalational mode is rare. It is caused by reduction and oxidation cycles, as well as the formation of reactive oxygen species, necessitating hemodialysis as the treatment. Without a clear history, a specific clinical trait, or a diagnostic test, diagnosis can be difficult. Our case thus highlights the inhaled paraquat poisoning, presenting with acute kidney injury with late respiratory impairment as a consequence.

Structurally Diverse Macrolactams from an Antarctic Streptomyces Species.

Twelve new polyenic macrolactams, cyclamenols G-R (1 and 3-13), together with the known analogue cyclamenol A (2), were isolated from Streptomyces sp. OUCMDZ-4348. Their structures were elucidated by spectroscopic analysis, quantum chemical calculations, chemical derivatizations, and Mosher's methods. The sequenced genome of OUCMDZ-4348 revealed the putative biosynthetic gene cluster of cyclamenols. It was proposed that the polycyclic natural products, cyclamenols H-R, might be formed from cyclamenols A and G through nonenzymatic intramolecular cycloadditions and oxidative cyclizations.