Good Tolerance Research Articles

Iron-Catalyzed One-Pot Cascade Reactions of Oximes with Inactivated Saturated Ketones: Entry to Highly Substituted Pyridines.

An iron-catalyzed oxidative [3 + 3] annulation of oxime esters with inactivated saturated ketones is described. This cascade strategy allows one-step rapid synthesis of various structurally important pyridines through an oxidative dehydrogenation/annulation/oxidative aromatization sequence via direct α,β-dehydrogenation of simple saturated ketones followed by annulation with oximes. This method shows good functional group tolerance, readily accessible starting materials, a wide substrate scope, high chemoselectivity, and no need for extra stoichiometric oxidant and is also applicable to the late-stage functionalization of natural products.

HFIP-Mediated Synthesis of 4-Aryl-NH-1,2,3-Triazoles and 1,5-Disubstituted 1,2,3-Triazolyl Glycoconjugates.

We herein report a multicomponent reaction for the synthesis of N-unsubstituted-1,2,3-triazoles and N-substituted-1,2,3 triazoles from the reaction of aldehydes, nitroalkanes, and sodium azides/glycosyl azides in the presence of 1,1,1,3,3,3-hexafluoroisopropanol, a hydrogen bond-donating reaction medium. This three-component reaction provides a metal-free strategy for sequentially forming one C-C and two C-N bonds in a one-pot fashion. One-pot mild reaction condition, operational simplicity, wide substrate scope, good functional group tolerance, easy purification, high reaction yields, and altogether excellent regioselectivity are the notable advantages of this 1,2,3-triazole-forming protocol. Moreover, this protocol provides practical access to the gram-scale synthesis of potent inhibitors of indoleamine 2,3-dioxygenase 1.

Reductive Coupling of N-Heteroarenes and 1,2-Dicarbonyls for Direct Access to γ-Amino Acids, Esters, and Ketones Using a Heterogeneous Single-Atom Iridium Catalyst.

Despite their significant importance, the challenges in direct and diverse synthesis of N-heterocyclic γ-amino acids/esters/ketones hamper exploration of their applications. Herein, by developing a multifunctional heterogeneous iridium single-atom catalyst composed of silica-confined iridium species and a boron-doped ZrO2 support (Ir-SAs@B-ZrO2/SiO2), we describe its utility in establishing a new reductive coupling reaction of N-heteroarenes and 1,2-dicarbonyls for selective and diverse construction of the as-described compounds in a straightforward manner. The striking features, including good substrate and functionality tolerance, high step and atom economy, exceptional catalyst reusability, and diversified product post-transformations, highlight the practicality of the developed chemistry. Mechanistic studies reveal that the synergy between the active Ir sites and acidic support favors a chemoselective reduction of the more inert N-heteroarenes and affords requisite enamine intermediates. In this work, the concept on precise transformation of reductive intermediates will open a door to further develop useful tandem reactions by rational catalyst design.

Synthesis of Indole- and Benzofuran-Based Benzylic Sulfones by Palladium-Catalyzed Sulfonylation of ortho-Iodoaryl Allenes.

A highly efficient palladium-catalyzed domino coupling reaction of ortho-iodoaryl allene with sodium sulfonates under mild conditions is described. This novel method provides a practical protocol to access diverse indole- and benzofuran-containing sulfones by simultaneous construction of C(sp2)-C(sp2) bond and a C(sp3)-S bonds in one pot. The salient features of this transformation include simple operations, broad substrate scope, and good functional group tolerance.

A Review of Contemporary Image Guidance Techniques in Head and Neck Cancer.

Traditional head and neck cancer treatment involves open surgery, cytotoxic chemotherapy, and conventional radiotherapy planning. Emerging techniques aim to improve precision and reduce associated toxicity and functional impairment in current practice. This review article describes four such adaptations in image guidance, tailored to next generation therapies. This is a review of current literature, including feasibility studies from our cancer center, relating to: saline-aided intra-oral ultrasound-guided retropharyngeal biopsy; intra-oral ultrasound guided trans-oral robotic surgery (TORS); ultrasound-guided injection of "directly injectedtherapies"; and magnetic resonance imaging-guided radiotherapy. Presented within the context of the wider literature, initial local experience and data indicate good technical outcomes and patient tolerance, and low technical complications in all four image guidance techniques. Initial findings suggest a potentially important future role for these four image guidance techniques, on which next generation therapies are reliant. The broader implications on cross-disciplinary collaboration are also explored herein.

Measuring the radiation hardness of terahertz devices for space applications

The application of terahertz technology in space is frontier for the development of 6G technologies. Terahertz transceiver devices based on gallium arsenide Schottky barrier diodes (GaAs SBDs) have the characteristics of small size, light weight and low power consumption, making them suitable for application on spacecraft. However, there is currently a lack of experimental assessments on their space adaptability. Here, we study the radiation hardness of terahertz devices to determine their adaptability in complex space environments. We exposed GaAs SBDs and terahertz multipliers as typical terahertz devices to gamma rays and protons. The experimental results showed that the terahertz devices exhibited good tolerance to protons, but prolonged exposure to gamma rays could significantly increase the leakage current of the GaAs SBDs and alter its C-V characteristics, leading to the failure of the terahertz multiplier. Nevertheless, the terahertz devices maintained a good level of radiation hardness, making them highly suitable for use in Low Earth Orbit (LEO) satellites. The comparison between the results of proton and gamma ray tests indicated that the terahertz devices exhibited high inherent radiation hardness against displacement damage but were more sensitive to ionization damage, requiring higher shielding requirements.

Once-a-Week Ablative Radiotherapy as Replacement of Prolonged Fractionation in Frail Patients: Feasibility and Toxicity Results

Introduction The aim of this work was to explore the use of an original once-weekly radiotherapy fractionation in elderly or frail patients with recurrence or metastasis from different solid malignancies. Material and Methods A retrospective analysis was conducted on 29 patients treated from 2011 to 2019 with a once-weekly radiotherapy schedule. Patients received a median dose of 27.5 Gy, with weekly fractions of 4-5 Gy over 7-10 weeks. The treatment aimed at both palliative and cytoreductive objectives. Primary endpoints were feasibility and compliance, secondary outcome was acute toxicity. Results All patients completed the planned radiotherapy without interruptions. Acute toxicity was mild, with only one patient developing grade 3 toxicity (bowel perforation). Three months post-treatment, 74% of patients experienced symptom relief and tumor response. One-year local control rates were 26.7%, and treatment was generally well-tolerated. Conclusion This once-weekly hypofractionated radiotherapy regimen demonstrated feasibility, good tolerance, and promising tumor response in frail and elderly patients. Although limited by a small sample size, the approach offers a practical alternative for patients unable to undergo conventional daily radiotherapy. Further studies on larger cohorts are required to validate these findings.

6π 1,5-Diaza-electrocyclization of Isatin, α-Ketoester Derived Hydrazones with α,β-Unsaturated Ketoesters, Ketones, and Aldehydes Enables Functionalized Pyrazoles.

A novel and efficient 6π 1,5-diaza-electrocyclization of readily available isatin, α-ketoester derived hydrazones with α,β-unsaturated ketoesters, ketones, and aldehydes has been developed. A series of functionalized pyrazoles bearing an oxindole unit were easily afforded by this tool with good yields and high functional group tolerance under mild conditions. Importantly, the obtained pyrazole could be further converted to 3-pyrazolecarboxylic acid with a quaternary carbon stereocenter.

Anode material determined divergent 5‐<i>exo</i>‐<i>dig</i> cyclization of <i>N</i>‐cyano‐2‐halobenzamides toward 3‐iminoisoindolin‐1‐ones and 3‐aminoisoindolin‐1‐ones

Herein, an electroreductive aryl radical enabled 5‐exo‐dig cyclization of N‐cyano‐2‐halobenzamides is presented, providing a convenient route for the synthesis of a variety of 3‐iminoisoindolin‐1‐ones in 30–75% yields. Simply by employing zinc plate instead of graphite rod anode, the products of the electrosynthesis are switched to diverse 3‐aminoisoindolin‐1‐ones through aryl‐radical‐mediated 5‐exo‐dig cyclization and subsequent reductive hydrogenation. Furthermore, this anode material determined divergent 5‐exo‐dig cyclization features mild electrochemical conditions, excellent substrate scopes, and good functional group tolerance.

Reversal of Reactivity of Heyns Intermediate for the Concise Synthesis of Substituted 3-Hydroxyquinolines.

An efficient and general method for the synthesis of 3-hydroxyquinolines has been achieved from o-acylanilines and α-hydroxyketones in good yields. The strategy involves the intramolecular reverse trapping of the in situ generated aminoenol intermediate with an electrophilic carbonyl, viz. an interrupted Heyns rearrangement, followed by aromatization. Important features include good functional group tolerance, operational simplicity, gram-scale synthesis, and broad synthetic utility.

Reductive Dehalogenation towards Olefins Mediated by Phase-Transfer Electrocatalysis

AbstractMild biphasic conditions enable dibutylviologen salts to act as both phase-transfer catalysts and electrocatalysts for the electroreduction of vicinal dibromides. Optimized experimental reaction conditions permit the production of the corresponding alkenes in competitive yields for a wide range of activated and nonactivated substrates, demonstrating good functional-group tolerance.

Iodine(III)-Mediated Keto-oximation of O-Alkynyl Hydroxylamines: ARoute to 3-Acyl Isoxazolines and 1,2-Oxazines.

An intramolecular iodine(III)-mediated keto-oximation of O-alkynyl hydroxylamines offers rapid and straightforward access to 3-acyl Δ2-isoxazolines and 1,2-oxazines. This approach features mild, metal-free, and aerobic reaction conditions with good functional group tolerance. Moreover, the synthetic utility of this method is demonstrated by the synthesis of unique structural motifs such as isoxazolidine, 3-vinyl isoxazoline, and 2,5-diphenylpyrazine derivatives by the conversion of 3-acyl Δ2-isoxazolines, thereby showcasing its efficiency and applicability in synthetic chemistry.

Beyond soybean meal: investigating the effects of dietary protein alternatives on gut health, liver function and microbiota in traditional slow-growing chicken breeds

The use of soybean meal in animal feed is crucial for nutrition but has a significant environmental impact, especially related to deforestation and biodiversity loss. With the increasing demand for sustainable agricultural practices, it becomes essential to explore alternatives to soybean meal. This study evaluated the effect of a soy-free diet, replaced with fava beans and pea protein, on an Italian slow-growing chicken breed: the Bianca di Saluzzo. The results indicate that the experimental diet did not compromise the growth, final weight or intestinal health of the animals, demonstrating a good tolerance and adaptability of the breed to these alternative ingredients. Furthermore, the analysis of the intestinal microbiota showed a positive impact, with an increase in organic acids such as succinic and citric, which could improve intestinal health and metabolic efficiency. Some changes in liver enzyme levels were observed, such as the increase in glutamate-oxaloacetate transaminase, an enzyme involved in amino acid metabolism. This increase could indicate a higher efficiency in protein metabolism, suggesting that the diet based on alternative ingredients could support an improvement in liver metabolism. Although this aspect deserves further investigation, it could represent a positive effect of the diet on liver function and overall health of the animals. Further studies are needed to fully understand the long-term implications of these dietary modifications, particularly in relation to the gut microbiota and metabolism.

Photocatalyst‐Free Visible‐Light Induced Radical Difluoromethylation/Cyclization Cascade Reaction for the Synthesis of Difluoromethylated Oxindoles with Difluoromethyl Phenoxathiinium Salt

AbstractA photocatalyst‐free photoinduced radical difluoromethylation approach for the convenient synthesis of difluoromethylated oxindoles from N‐arylacrylamides with difluoromethyl phenoxathiinium salt (PT‐CF2H+BF4−) was developed, this transformation involves radical difluoromethylation/cyclization cascade process and features photocatalyst‐free, mild reaction conditions, broad substrate scope and good functional groups tolerance. With this method, a wide variety of N‐arylacrylamides were successfully converted to desired difluoromethylated oxindoles in good to excellent yields.

Electrooxidative Ni-Catalyzed Decarboxylation of Arylacetic Acids Towards the Synthesis of Carbonyls under Air Conditions.

After systematic realization of decarboxylative functionalization of carboxylic acids under heating conditions in our group, we herein reported an electrochemical method for Ni-catalyzed decarboxylative oxygenation of arylacetic acids under open air conditions. The protocol provided corresponding carbonyls including aldehydes and ketones in moderate to satisfactory yields with good functional group tolerance, furthermore, the practicability and advantage of the method was highlighted through Ni-catalyzed oxidative decarboxylation of carboxylic acid-containing drugs and preformation of scalable transformation. Mechanistic studies demonstrated that the possible involvement of free radical intermediate in the conversion.

Photocatalytic One-Pot Three-Component Reaction for the Regioselective Synthesis of Bromo-Substituted Pyrazoles.

A photocatalytic three-component cascade reaction of readily available enaminones, hydrazines, and CBr4 for the synthesis of bromo-substituted pyrazoles in one pot has been demonstrated. This strategy involves intermolecular C-N/C-Br bond formation and represents an efficient approach to the construction of 4-bromo-substituted pyrazoles with high regioselectivity, broad substrate scope, good functional group tolerance, convenient operation, and mild reaction conditions. Mechanistic investigations show that this reaction proceeds via intermolecular cyclization of enaminones with hydrazines, followed by a regioselective bromination of pyrazoles using CBr4 as a "Br" source.

Palladium‐Catalyzed Cyclization/Thiocarbonylation for the Synthesis of Thioester‐Substituted Benzofurans with S‐Aryl Thioformates as the Thioester Sources

AbstractA palladium‐catalyzed cyclization and thiocarbonylation reaction is disclosed for the synthesis of thioester‐containing benzofurans. By using S‐aryl thioformates as efficient and convenient thioester surrogates, a variety of thioester‐functionalized benzofurans were formed in moderate to excellent yields with very good functional group tolerance. This protocol features mild reaction conditions, broad substrate scope, and no manipulation of toxic CO gas and odorous thiols.

Evaluation of fermentative activities of yeasts isolated from guava fruit (Psidium guajava L.)

The study was conducted to isolate and screen yeast strains having good fermentative activities for wine production from guava (Psidium guajava L.). Yeasts were isolated from 22 samples of ripe guava fruits (including 4 varieties: Cattley, Taiwan, Ruby Supreme and Queen), which were collected from 6 provinces in the Mekong Delta. The yeast isolates were examined for biological characteristics, including colonial morphology and cell shape, after 48 h of culture, and investigated for fermentative characteristics including production of H2S gas, temperature and ethanol tolerance, ability to flocculate, production of extracellular enzymes, and fermentation of carbohydrate sources. The results showed that 33 yeast strains were isolated based on colony and cell morphologies. There were 9 isolates from the Taiwan variety, 13 isolates from the Queen variety, 7 isolates from the Cattley variety, and 4 isolates from Ruby supreme. Ten out of 33 isolates did not produce H₂S gas and had good flocculent ability in the fermentative solution after 7 days. Among them, the five yeast isolates (named NHCB1, NHCL4, NHCB4, DLCL1, and NHCB2) had good temperature tolerance at 39°C - 43°C, and high ethanol tolerance at 6% - 8% within 24 h. Three isolates (NHCL4, NHCB2, and NHCB4) with good ability to ferment glucose and fructose were selected for sequencing. The internal transcribed spacer sequences of all three strains were identical to those of Hanseniaspora opuntiae (> 99% identity). Briefly, this yeast strain can tolerate ethanol, ferment, and produce an appealing smell, bringing the potential for the production of wine or other fermented products.

Cobalt‐Catalyzed Synthesis of Functionalized Nordazepams and Benzimidazoquinazolines and Their Photophysical Properties

Abstract: An efficient and environmentally friendly one‐pot sequential synthesis of functionalized nordazepam and a benzimidazoquinazoline analogue is reported, utilizing cobalt as the metal catalyst. The reaction proceeds via either the α‐alkenylation or dehydrogenative sp3 C‐H functionalization pathway. This transformation includes mild reaction conditions, operational simplicity, and good functional group tolerance. Additionally, this method is suitable for the gram‐scale synthesis of functionalized nordazepam and benzimidazoquinazoline compounds. Furthermore, the synthetic utility, photophysical properties and real‐life application of the synthesized derivatives were explored.

PtCl2-Catalyzed Intramolecular Cyclization of α-Benzyl Allenoates to Afford Indenes and Furanones.

Indene and furanone are important ring structures widely present in active pharmaceutical molecules. Here, we have developed a straightforward method for the synthesis of indene and furanone via PtCl2-catalyzed intramolecular cyclization of α-benzyl allenoates. By altering the ester substitution pattern in the α-benzyl allenoates, we can regulate the reaction site, enabling two distinct intramolecular cyclization reactions that yield both indene and furanone products, respectively. For α-benzyl-substituted ethyl allenoate, the reaction proceeds via a 5-exo cyclization to form indene derivatives. In contrast, for α-benzyl-substituted tert-butyl allenoate, the reaction involves ester hydrolysis and intramolecular cyclization, yielding furanone products. This method operates efficiently under a 5 mol % PtCl2 catalyst and exhibits good tolerance toward various functional groups. Furthermore, furanone products can be obtained on a gram scale and further smoothly converted into 1,2-disubstituted furan.