The enantioselective assembly of quaternary stereocenters through sequential functionalization of versatile carbon-atom precursors has the potential to systematize the synthesis of these ubiquitous ...stereogenic elements. Herein, we report two catalytic processes that allow the realization of this concept in the enantioselective synthesis of cyclopropanes. We demonstrate that C–H functionalization, carbene-transfer, and decarboxylative cross-coupling can sequentially take place in the same carbon atom to obtain highly enantioenriched cyclopropane products. The reactions reported herein give access to redox-active analogues of privileged aryldiazoacetates and demonstrate their enantioselective carbene transfer with a simple and practical rhodium catalyst.
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.
Going to the source: The asymmetric synthesis of cyclopropanes is currently designed using specific strategies that depend on the materials available and the final functionality of each target. Presented here is a comprehensive approach that engages simple feedstocks, including aliphatic olefins, with a single redox‐active carbene precursor (NHPI‐DA), which acts as a universal source for a chiral C−H unit.
The first multicomponent catalytic asymmetric synthesis of spiroacetals has been described. Hybrid molecules comprising a spiroacetal scaffold (a natural-product inspired scaffold) and an α-amino ...acid motif (a privileged fragment) are easily available through a gold phosphate-catalysed one-pot three component coupling reaction of alkynols, anilines and glyoxylic acid.
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.
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.
Review clinical results of the treatment for acetabular fractures using the pararectus approach and analyze surgical variations of the traditional approach.
Retrospective.
Tertiary referral hospital.
...46 patients over 65 years of age who sustained an acetabular fracture and underwent surgery using the pararectus approach.
Fractures were treated using a pararectus approach. Three variations of the original technique were performed: (1) Ligature of the deep iliac circumflex artery and vein, (2) separation of the psoas and iliacus muscles, and (3) isolation of the spermatic cord in men and round ligament in women together with the iliac and epigastric vessels.
Outcomes measures included surgical, demographic, and clinical data, and information related to follow-up.
Duration of surgery, 125 minutes (95-210). Quality of reduction on postoperative computed tomography (CT) scan; anatomic in 22 patients (47.8%), incomplete in 16 (34.8%), and poor in 8 (17.4%). In patients in whom the hip was preserved (n = 41), functional status was excellent in 15 patients (36.5%), good in 17 (41.4%), fair in 6 (14.7%), and poor in 3 (7.4%), with mean functional score of 16 points (7-18). Seven patients (15.2%) developed posttraumatic osteoarthritis and 4 of these patients underwent total hip replacement.
This study reports positive outcomes in fracture reduction and clinical outcomes with low complications in older patients who suffered acetabular fractures and were treated using a pararectus approach. Small variations in the technique, such as those proposed in this study, may help to widen access to the surgical site and simplify the technique.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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.
Trimethylaluminum promotes the first 3+2 azomethine ylide cycloadditions that engage non‐electrophilic olefins. This reaction allows the stereoselective combination of abundant feedstocks to access new polar polydentate scaffolds for ligand design.
The direct preparation of ketones from carboxylate anions is greatly limited by the required use of organolithium reagents or activated acyl sources that need to be independently prepared. Herein, a ...specific magnesium amide additive is used to activate and control the addition of more tolerant Grignard reagents to carboxylate anions. This strategy enables the modular synthesis of ketones from CO2 and the preparation of isotopically labeled pharmaceutical building blocks in a single operation.
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.
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