Uncatalyzed Diboron Activation by a Strained Hydrocarbon: Experimental and Theoretical Study of [1.1.1]Propellane Diborylation.

The synthesis of strained carbocyclic building blocks is relevant for Medicinal Chemistry, and methylenecyclobutanes are particularly challenging with current synthetic technology. Careful inspection of the reactivity of [1.1.1]propellane and diboron reagents has revealed that bis(catecholato)diboron (B2cat2) can produce a bis(borylated) methylenecyclobutane in a few minutes at room temperature. This reaction constitutes the first example of B-B bond activation by a special apolar hydrocarbon and also the first time that propellane is electrophilically activated by boron. Mechanistic studies including in situ NMR kinetics and DFT calculations demonstrate that the diboron moiety can be directly activated through coordination with the inverted sigma bond of propellane, and reveal that DMF is involved in the stabilization of diboronate ylide intermediates rather than the activation of the B-B bond. These results enable new possibilities for both diboron and propellane chemistry, and for further developments in the synthesis of methylenecyclobutanes based on propellane strain release.

Direct Addition of Grignard Reagents to Aliphatic Carboxylic Acids Enabled by Bulky turbo-Organomagnesium Anilides.

Invited for the cover of this issue is the group of Abraham Mendoza at Stockholm University. The image depicts a Grignard reagent "turbo-charged" with a magnesium anilide additive. Read the full text of the article at 10.1002/chem.202104053.

Direct Addition of Grignard Reagents to Aliphatic Carboxylic Acids Enabled by Bulky turbo-Organomagnesium Anilides.

The synthesis of ketones through addition of organometallic reagents to aliphatic carboxylic acids is a straightforward strategy that is limited to organolithium reagents. More desirable Grignard reagents can be activated and controlled with a bulky aniline-derived turbo-Hauser base. This operationally simple procedure allows the straightforward preparation of a variety of aliphatic and perfluoroalkyl ketones alike from functionalized alkyl, aryl and heteroaryl Grignard reagents.

Curcumin Modifies the Activity of Plasmatic Antioxidant Enzymes and the Hippocampal Oxidative Profile in Rats upon Acute and Chronic Exposure to Ozone.

Ozone (O3) is an oxidating tropospheric pollutant. When O3 interacts with biological substrates, reactive oxygen and nitrogen species (RONS) are formed. Severe oxidative damage exhausts the endogenous antioxidant system, which leads to the decreased activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Curcumin (CUR) is a natural polyphenol with well-documented antioxidant and anti-inflammatory properties. The aim of this work is to evaluate the effects of curcumin on CAT, GPx, and SOD activity and the inhibition of oxidative damage after the acute and chronic exposure to O3. Fifty male Wistar rats were divided into five experimental groups: the intact control, CUR-fed control, exposed-to-O3 control, CUR-fed (preventive), and CUR-fed (therapeutic) groups. These two last groups received a CUR-supplemented diet while exposed to O3. These experiments were performed during acute- and chronic-exposure phases. In the preventive and therapeutic groups, the activity of plasma CAT, GPx, and SOD was increased during both exposure phases, with slight differences; concomitantly, lipid peroxidation and protein carbonylation were inhibited. For this reason, we propose that CUR could be used to enhance the activity of the antioxidant system and to diminish the oxidative damage caused by exposure to O3.

Computational and Experimental Study of Turbo-Organomagnesium Amide Reagents: Cubane Aggregates as Reactive Intermediates in Pummerer Coupling.

The dynamic equilibria of organomagnesium reagents are known to be very complex, and the relative reactivity of their components is poorly understood. Herein, a combination of DFT calculations and kinetic experiments is employed to investigate the detailed reaction mechanism of the Pummerer coupling between sulfoxides and turbo-organomagnesium amides. Among the various aggregates studied, unprecedented heterometallic open cubane structures are demonstrated to yield favorable barriers through a concerted anion-anion coupling/ S-O cleavage step. Beyond a structural curiosity, these results introduce open cubane organometallics as key reactive intermediates in turbo-organomagnesium amide mixtures.

Temperature should not be measured on forearm with infrared thermometers for Covid-19 screening.

Not available.

Curcumin Decreases Hippocampal Neurodegeneration and Nitro-Oxidative Damage to Plasma Proteins and Lipids Caused by Short-Term Exposure to Ozone.

Neurodegeneration is the consequence of harmful events affecting the nervous system that lead to neuronal death. Toxic substances, including air pollutants, are capable of inducing neurodegeneration. Ozone (O3) is the most oxidative toxic pollutant. O3 reacts with cellular components and forms reactive oxygen and nitrogen species, triggering nitro-oxidative damage during short-term exposure. Curcumin (CUR) is a natural phenolic molecule bearing well-documented antioxidant and anti-inflammatory biological activities in diverse experimental models. The aim of this work was to evaluate the effect of preventive dietary administration of CUR against hippocampal neurodegeneration and nitro-oxidative damage caused by short-term exposure to O3. Eighty Wistar male rats were distributed into four experimental groups, twenty rats each: intact control; CUR dietary supplementation without O3 exposure; exposure to 0.7 ppm of O3; and exposed to O3 with CUR dietary supplementation. Five rats from each group were sacrificed at 1, 2, 4, and 8 h of exposure. The CUR dose was 5.6 mg/kg and adjusted according to food consumption. CUR significantly decreased oxidative damage to plasma lipids and proteins, as well as neurodegeneration in CA1 and CA3 hippocampal regions. Concluding, CUR proved effective protection in decreasing neurodegeneration in the hippocampus and prevented systemic oxidative damage.

Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light.

Photoexcited dihydronicotinamides like NADH and analogues have been found to generate alkyl radicals upon reductive decarboxylation of redox-active esters without auxiliary photocatalysts. This principle allowed aliphatic photocoupling between redox-active carboxylate derivatives and electron-poor olefins, displaying surprising water and air-tolerance and unusually high coupling rates in dilute conditions. The orthogonality of the reaction in the presence of other carboxylic acids and its utility in the functionalization of DNA is presented, notably using visible light in combination with NADH, the ubiquitous reductant of life.

Dietary Curcumin Prevented Astrocytosis, Microgliosis, and Apoptosis Caused by Acute and Chronic Exposure to Ozone.

Ozone is the most oxidant tropospheric pollutant gas, causing damage through the formation of reactive oxygen and nitrogen species. Reactive species induce the nuclear factor-kappa B (NF-κB) activation leading to neuroinflammation characterized by astrocytosis, microgliosis, and apoptotic cell death. There is interest in evaluating the pharmacological activity of natural antioxidants to confer neuroprotection against the damage caused by ozone in highly polluted cities. Curcumin has been proven to exert a protective action in the central nervous system (CNS) of diverse experimental models, with no side effects. The aim of this work is to evaluate the effect of curcumin in a preventive and therapeutic manner against the astrocytosis, microgliosis, and apoptosis induced by ozone in rat hippocampus. Fifty Wistar rats were distributed into five experimental groups: The intact control, curcumin fed control, ozone-exposed group, and the preventive and therapeutic groups receiving the curcumin supplementation while exposed to ozone. Ozone caused astrocytosis and microgliosis, as well as apoptosis in the hippocampus. Meanwhile, curcumin was able to decrease the activation of microglia and astrocytes, and apoptotic cell death in both periods of exposure. Therefore, we propose that curcumin could be used as a molecule capable of counteracting the damage caused by ozone in the CNS.

General Cyclopropane Assembly by Enantioselective Transfer of a Redox-Active Carbene to Aliphatic Olefins.

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates, and reagents, even when targeting similar compounds. This approach slows down discovery and limits available chemical space. Introduced herein is a practical and versatile diazocompound and its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. The redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect allowed the asymmetric cyclopropanation of various olefins, including unfunctionalized aliphatic alkenes, that enables the three-step total synthesis of (-)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons.

Mechanistic Insight into Enantioselective Palladium-Catalyzed Oxidative Carbocyclization-Borylation of Enallenes.

The asymmetric palladium-catalyzed oxidative carbocyclization-borylation of enallenes, employing a chiral phosphoric acid as co-catalyst, constitutes an efficient and convenient entry into functionalized building blocks with cyclopentene scaffolds in high enantiopurity. Up till now there has been a lack of knowledge concerning the origin of enantioselectivity of this reaction as well as the absolute configuration of the product. Herein, we report the crystal structure of one of the compounds generated via this carbocyclization, providing the link between the configuration of the products and the configuration of the chiral phosphoric acid used in the reaction. Furthermore, the origin of the enantioselectivity is thoroughly investigated with density functional theory (DFT) calculations. By careful examination of different possible coordination modes, it is shown that the chiral phosphoric acid and the corresponding phosphate anion serve as ligands for palladium during the key stereoselectivity-determining cyclization step. In addition, we examine reactions wherein an extra chiral reagent, a p-benzoquinone containing a chiral sulfoxide, is used. The combined experimental and theoretical studies provide insight into the details of complexation of palladium with various species present in the reaction mixture, furnishing a general understanding of the factors governing the stereoselectivity of this and related catalytic reactions.

Intermolecular Pummerer Coupling with Carbon Nucleophiles in Non-Electrophilic Media.

A new Pummerer-type C-C coupling protocol is introduced based on turbo-organomagnesium amides, which unlike traditional Pummerer reactions, does not require strong electrophilic activators, engages a broad range of C(sp3 )-, C(sp2 )-, and C(sp)-nucleophiles, and seamlessly integrates with C-H and C-X magnesiation. Given the central character of sulfur compounds in organic chemistry, this protocol allows access to unrelated carbonyls, olefins, organometallics, halides, and boronic esters through a single strategy.

Direct and Stereospecific [3+2] Synthesis of Pyrrolidines from Simple Unactivated Alkenes.

Pyrrolidines are important heterocyclic compounds with endless applications in organic synthesis, metal catalysis, and organocatalysis. Their potential as ligands for first-row transition-metal catalysts inspired a new method to access complex poly-heterocyclic pyrrolidines in one step from available materials. This fundamental step forward is based on the discovery of an essential organoaluminum promoter that engages unactivated and electron-rich olefins in intermolecular [3+2] cycloadditions.

Scalable Synthesis of Piperazines Enabled by Visible-Light Irradiation and Aluminum Organometallics.

The development of more active C-H oxidation catalysts has inspired a rapid, scalable, and stereoselective assembly of multifunctional piperazines through a [3+3] coupling of azomethine ylides. A combination of visible-light irradiation and aluminum organometallics is essential to promote this transformation, which introduces visible-light photochemistry of main-group organometallics and sets the basis for new and promising catalysts.

Two-phase synthesis of (-)-taxuyunnanine D.

The first successful effort to replicate the beginning of the Taxol oxidase phase in the laboratory is reported, culminating in the total synthesis of taxuyunnanine D, itself a natural product. Through a combination of computational modeling, reagent screening, and oxidation sequence analysis, the first three of eight C-H oxidations (at the allylic sites corresponding to C-5, C-10, and C-13) required to reach Taxol from taxadiene were accomplished. This work lays a foundation for an eventual total synthesis of Taxol capable of delivering not only the natural product but also analogs inaccessible via bioengineering.

Nitrooxidative Stress and Neuroinflammation Caused by Air Pollutants Are Associated with the Biological Markers of Neurodegenerative Diseases.

Millions of people around the world are exposed to air pollutants, such as particulate matter 2.5 (PM2.5) and ozone (O3). Such exposure usually does not exclude these two types of pollutants and their harmful effects could be additive or synergistic. O3 is a highly oxidizing gas that reacts with the cellular environment just as PM2.5, triggering nitrooxidative damage. Once nitrooxidative stress overcomes the endogenous antioxidant system, an acute neuroinflammatory process is generated, and once it becomes chronic, it favors the formation of neurodegenerative disease markers. The presence of these markers becomes potentially dangerous in people who have a genetic predisposition and are at a higher risk of developing neurodegenerative diseases such as Alzheimer's and Parkinson's. Our experimental approach for nitrooxidative damage and neuroinflammation caused by air pollutants has focused on the exposure of rats to O3 in an isolated chamber. The hippocampus is the most studied brain structure because of its neuronal connectivity network with the olfactory epithelium, its weak antioxidant defense, and its fundamental roll in cognitive processes. However, other brain structures may exhibit a different degree of damage upon exposure to O3 and PM2.5, making their involvement an important factor in developing other CNS diseases. The age spectrum for augmented sensibility to air pollutants seems to mostly affect the pre-postnatal (autism spectrum) period and the elderly (neurodegenerative). Thus, a new approach could be the estimation of the damage caused by PM2.5 and O3 through a controlled exposure paradigm to determine the extent of damage caused by both pollutants.

Total synthesis of taxane terpenes: cyclase phase.

A full account of synthetic efforts toward a lowly oxidized taxane framework is presented. A non-natural taxane, dubbed "taxadienone", was synthesized as our first entry into the taxane family of diterpenes. The final synthetic sequence illustrates a seven-step, gram-scale and enantioselective route to this tricyclic compound in 18% overall yield. This product was then modified further to give (+)-taxadiene, the lowest oxidized member of the taxane family of natural products.

Modular Synthesis of (Borylmethyl)silanes through Orthogonal Functionalization of a Carbon Atom.

(Borylmethyl)trimethylsilanes are important building blocks in organic synthesis displaying a unique reactivity. Yet, the synthesis of more advanced derivatives is limited by the advanced silicon intermediates required for their preparation. Herein, a one-pot synthesis of (borylmethyl)silanes is developed, sourced on available alkyl-, aryl-, alkoxy-, aryloxy-, and silyl-hydrosilane materials. The privileged reactivity of N-hydroxyphthalimidyl diazoacetate (NHPI-DA) in Si-H insertion and α-silyl redox-active esters in different decarboxylative borylation reactions are scrutinized.

Effective Removal of Cu2+ Ions from Aqueous Media Using Poly(acrylamide-co-itaconic acid) Hydrogels in a Semi-Continuous Process.

Adsorption is one of the most crucial processes in water treatment today. It offers a low-cost solution that does not require specialized equipment or state-of-the-art technology while efficiently removing dissolved contaminants, including heavy metals. This process allows for the utilization of natural or artificial adsorbents or a combination of both. In this context, polymeric materials play a fundamental role, as they enable the development of adsorbent materials using biopolymers and synthetic polymers. The latter can be used multiple times and can absorb large amounts of water per gram of polymer. This paper focuses on utilizing adsorption through hydrogels composed of poly(acrylamide-co-itaconic acid) for removing Cu2+ ions dissolved in aqueous media in a semi-continuous process. The synthesized hydrogels were first immersed in 0.1 M NaOH aqueous solutions, enabling OH- ions to enter the gel matrix and incorporate into the polymer surface. Consequently, the copper ions were recovered as Cu(OH)2 on the surface of the hydrogel rather than within it, allowing the solid precipitates to be easily separated by decantation. Remarkably, the hydrogels demonstrated an impressive 98% removal efficiency of the ions from the solution in unstirred conditions at 30 °C within 48 h. A subsequent study involved a serial process, demonstrating the hydrogels' reusability for up to eight cycles while maintaining their Cu2+ ion recovery capacity above 80%. Additionally, these hydrogels showcased their capability to remove Cu2+ ions even from media with ion concentrations below 100 ppm.