Synthesis of 4-Alkyl-2-chloro Imidazoles Using Intermolecular Radical Additions.

Here, we report an intermolecular radical addition-based reaction sequence that permits preparation of functionalized imidazoles via a 5-step/3-pot procedure. In contrast to traditional, transition-metal mediated protocols, which generally provide access to 2-substituted imidazoles, the strategy described here allows incorporation of a structurally diverse range of complex alkyl side chains at the 4-position. This work demonstrates that intermolecular free-radical addition reactions are a powerful alternative to traditional methods used to synthesize medicinally important heterocyclic frameworks.

α-Amido Trifluoromethyl Xanthates: A New Class of RAFT/MADIX Agents.

Xanthates have long been described as poor RAFT/MADIX agents for styrene polymerization. Through the determination of chain transfer constants to xanthates, this work demonstrated beneficial capto-dative substituent effects for the leaving group of a new series of α-amido trifluoromethyl xanthates, with the best effect observed with trifluoroacetyl group. The previously observed Z-group activation with a O-trifluoroethyl group compared to the O-ethyl counterpart was quantitatively established with Cex = 2.7 (3-4 fold increase) using the SEC peak resolution method. This study further confirmed the advantageous incorporation of trifluoromethyl substituents to activate xanthates in radical chain transfer processes and contributed to identify the most reactive xanthate reported to date for RAFT/MADIX polymerization of styrene.

Environmental impact of phytobiotic additives on greenhouse gas emission reduction, rumen fermentation manipulation, and performance in ruminants: an updated review.

Ruminal fermentation is a natural process involving beneficial microorganisms that contribute to the production of valuable products and efficient nutrient conversion. However, it also leads to the emission of greenhouse gases, which have detrimental effects on the environment and animal productivity. Phytobiotic additives have emerged as a potential solution to these challenges, offering benefits in terms of rumen fermentation modulation, pollution reduction, and improved animal health and performance. This updated review aims to provide a comprehensive understanding of the specific benefits of phytobiotic additives in ruminant nutrition by summarizing existing studies. Phytobiotic additives, rich in secondary metabolites such as tannins, saponins, alkaloids, and essential oils, have demonstrated biological properties that positively influence rumen fermentation and enhance animal health and productivity. These additives contribute to environmental protection by effectively reducing nitrogen excretion and methane emissions from ruminants. Furthermore, they inhibit microbial respiration and nitrification in soil, thereby minimizing nitrous oxide emissions. In addition to their environmental impact, phytobiotic additives improve rumen manipulation, leading to increased ruminant productivity and improved quality of animal products. Their multifaceted properties, including anthelmintic, antioxidant, antimicrobial, and immunomodulatory effects, further contribute to the health and well-being of both animals and humans. The potential synergistic effects of combining phytobiotic additives with probiotics are also explored, highlighting the need for further research in this area. In conclusion, phytobiotic additives show great promise as sustainable and effective solutions for improving ruminant nutrition and addressing environmental challenges.

Short Formal Syntheses of Lycorine and Congeners Using a 5-Endo-Trig/6-Endo-Trig Radical Cyclization Sequence.

Here, we report a practical route to medicinally interesting lycorine congeners alongside formal syntheses of various lycorine-type natural products, including lycorine itself. The efficiency of our strategy derives from a back-to-back 5-endo-trig/6-endo-trig radical cyclization sequence, which we systematically studied both experimentally and computationally. The results of our work will facilitate future development of urgently needed antiviral therapeutics based on lycorine.

Some Aspects of α-(Acyloxy)alkyl Radicals in Organic Synthesis.

The preparation and use of α-(acyloxy)alkyl xanthates to generate and capture α-(acyloxy)alkyl radicals is briefly reviewed. Their inter- and intramolecular additions to both activated and unactivated, electronically unbiased, alkenes, and to (hetero)aromatic rings, as well as their radical allylation and vinylation reactions are described. Application to the total synthesis of two 4-hydroxytetralone natural products is also presented.

A Versatile Route to Acyl (MIDA)Boronates.

A modular approach to highly functional acyl (MIDA)boronates is described. It involves the generation of the hitherto unknown radical derived from acetyl (MIDA)boronate and its capture by various alkenes, including electronically unbiased, unactivated alkenes. In contrast to the anion of acetyl (MIDA)boronate, which has not so far been employed in synthesis, the corresponding radical is well behaved and readily produced from the novel α-xanthyl acetyl (MIDA)boronate. This shelf-stable, easily prepared solid is a convenient acyl (MIDA)boronate transfer agent that provides a direct entry to numerous otherwise inaccessible structures, including latent 1,4-dicarbonyl derivatives that can be transformed into B(MIDA) substituted pyrroles and furans. A competition experiment indicated the acyl (MIDA)boronate substituted radical to be more stable than the all-carbon acetonyl radical but somewhat less reactive in additions to alkenes.

Ensiling Characteristics, In Vitro Rumen Fermentation Patterns, Feed Degradability, and Methane and Ammonia Production of Berseem (Trifolium alexandrinum L.) Co-Ensiled with Artichoke Bracts (Cynara cardunculus L.).

This study investigated the effect of co-ensiling increasing levels of artichoke bracts (Cynara cardunculus L.) with berseem (Trifolium alexandrinum L.) (100:0, 75:25, 50:50, 25:75, and 0:100, respectively) on silage quality after 0, 30, 60, and 120 days. Moreover, the in vitro rumen fermentation characteristics and methane (CH4) and ammonia (NH3-N) production were evaluated using a buffalo inoculum source. The results showed that pH of the silage and the concentration of acetic, propionic, butyric acid, and NH3-N significantly decreased (L; p < 0.01) with the increasing amounts of artichoke bracts in the mixture. At 30 and 60 days of ensiling, the highest lactic acid concentration was observed at intermediate proportions of artichoke bracts (p < 0.01). Cumulative gas production was higher in artichoke bracts than in the berseem silage. After 24 h of incubation, the highest value (p < 0.05) of truly dry matter, organic matter, natural detergent fiber degradability, and NH3-N concentration was recorded with 500 g/kg of forage mixtures. As the artichoke bract concentration increased, the partitioning factor and ruminal pH declined linearly (p ≤ 0.05). No significant differences were observed for total volatile fatty acids and volatile fatty acids molar proportions. In summary, co-ensiling artichoke bracts with berseem at a ratio of 1:1 might be a promising and easy method for the production of high-quality silage from legume forage with positively manipulating rumen fermentation.

Large-scale geological structures of the Egyptian Nubian Shield.

Integration of potential field- and structural data make it possible to trace surface and subsurface large-scale geological structures of the Egyptian Nubian Shield (ENS). Obtained results indicate that the Northern Eastern Desert (NED) of the ENS is dominated by relatively younger (c. 580 Ma) E-W and NE-SW trending extensional structures that were controlled by the evolution and retreat of the Cadomian Arc. Density of such extensional structures increases with depth as displayed by the potential data. The prevailing structural trends in the Central Eastern Desert (CED) are NW-SE and WNW-ESE. Both trends are highly prompted by the timing of deformation upon the Najd Fault System, and are themselves dissected by a relatively younger NE-SW shearing trend. Lineament density in the CED is subordinate for both subsurface and near surface structures. The South Eastern Desert exhibits compressional and extrusion-related structures of two main prominent trends; WNW-to-NW (to the western part) and the N-, NNE- to NE (to the eastern part). The previously mentioned Neoproterozoic trends are remarkably influenced by the Oligocene-Miocene Red Sea-Gulf of Suez rift related fractures in the vicinity of the rift shoulder. The remarkable change in trends and densities of structural trends, especially in the NED, is interpreted in terms of concealing of the older structures by the younger extensional structures which in turns reflect an N-ward progressive deformation in the entire ENS. Gravity data are more appropriate in delineating the structural trends compared to the magnetic data which are largely affected by lithological variations and/or alteration zones and magnetic mineralogy.

The xanthate route to tetralones, tetralins, and naphthalenes. A brief account.

The present account summarises routes to tetralones, tetralines, and naphthalenes based on the chemistry of xanthates developed in the authors' laboratory. The degenerative reversible transfer of xanthates allows radical addition even to unactivated, electronically unbiased alkenes, and tolerates a broad range of functional groups, in particular common polar groups such as esters, ketones, nitriles, amides, carbamates, etc. Xanthates also allow radical ring closures onto aromatic rings. This feature, in combination with the intermolecular addition to alkenes, can be used to construct tetralones and tetralines. With the appropriate appendages, the former can be converted into napthalenes with a variety of substitution patterns. This translates into a convergent approach to a vast array of building blocks of interest to the pharmaceutical and agrochemical industries, and to material sciences.

An Ionic-Radical Approach to Vicinally Functionalized Cyclopentanones and Cyclohexanones.

A versatile strategy to access vicinally functionalized cyclopentanones and cyclohexanones is described. It takes advantage of new reagents, α-xanthyl enones, which can be prepared from the reaction of xanthate salts with the corresponding epoxyketones under mild conditions. ß-Functionalization of these compounds can be performed by conjugate additions without affecting the xanthate moiety. This significantly expands the pool of xanthate substrates, allowing the synthesis of open chain and fused bicyclic building blocks useful in the synthesis of natural products.

Quantifying unused opioids following emergency and ambulatory care: A systematic review and meta-analysis.

Objective: To quantify unused opioids among adult and pediatric patients discharged from the emergency department (ED) or ambulatory care settings with a prescription for acute pain. Methods: We searched MEDLINE, Embase, CINHAL, PsycINFO, the Cochrane Library, and the gray literature from inception to April 29, 2021. We included observational studies in which any patient with an acutely painful condition received a prescription for an opioid on discharge from an outpatient care setting, and unused opioids were quantified. Two reviewers screened records for eligibility, extracted data, and conducted the quality assessment. Where possible, we pooled data and otherwise described the results of studies narratively. Total unused prescriptions were synthesized using a weighted average. Random effects models were used, and heterogeneity was measured by the I2 statistic. Our primary outcome was the quantity of unused opioid medication available after receiving a prescription for acute pain. Secondary outcomes were the proportion of patients with unused opioids following a prescription, the proportion of patients using no opioids, morphine equivalents of unused opioids, and factors associated with leftover opioids. Results: In this systematic review and meta-analysis of 9 studies in emergency and ambulatory care settings, 59.6% of prescribed opioids remained unused; pediatric patients had 69.3% of their prescriptions remaining, compared to 54.6% among adult patients. The highest proportion of unused opioids was found following dental extractions (82.6%). Conclusions and Relevance: More than 50% of opioids remain unused following prescriptions for acute pain. Responsible prescribing must be accompanied by education on safer use, storage, and disposal.

Potential of selected plant extracts to control severe subacute ruminal acidosis in vitro as compared with monensin.

BACKGROUND: In recent years, researchers have become increasingly interested in developing natural feed additives that can stabilize ruminal pH and thus prevent or eliminate the risk of severe subacute rumen acidosis. Herein, 3 experiments were conducted using a semi-automated in vitro gas production technique. In the experiment (Exp.) 1, the efficacy of 9 plant extracts (1.5 mg/ml), compared to monensin (MON; 12 µg/ml), to counteract ruminal acidosis stimulated by adding glucose (0.1 g/ml) as a fermentable carbohydrate without buffer was assessed for 6 h. In Exp. 2, cinnamon extract (CIN) and MON were evaluated to combat glucose-induced acidosis with buffer use for 24 h. In Exp. 3, the effect of CIN and MON on preventing acidosis when corn or barley grains were used as substrate was examined. RESULTS: In Exp. 1, cinnamon, grape seeds, orange, pomegranate peels, propolis, and guava extracts significantly increased (P < 0.05) pH compared to control (CON). Both CIN and MON significantly increased the pH (P < 0.001) but reduced cumulated gas production (P < 0.01) compared to the other treatments. In Exp. 2, the addition of CIN extract increased (P < 0.01) pH value compared to CON at the first 6 h of incubation. However, no significant differences in pH values between CIN and CON at 24 h of incubation were observed. The addition of CIN extract and MON decreased (P < 0.001) lactic acid concentration and TVFA compared to CON at 24 h. The CIN significantly (P < 0.01) increased acetate: propionate ratio while MON reduced it. In Exp. 3, both CIN and MON significantly increased (P < 0.05) ruminal pH at 6 and 24 h and reduced lactic acid concentration at 24 h compared to CON with corn as substrate. However, CIN had no effect on pH with barley substrate at all incubation times. CONCLUSIONS: It can be concluded that CIN can be used effectively as an alternative antibiotic to MON to control ruminal acidosis when corn is used as a basal diet.

A Radical Route to α-Substituted Enones.

A versatile strategy for the α-substitution of enones through the formal fusion between enones and unactivated alkenes is described. It relies on the formation and use of α-xanthyl-ß-hydroxy ketones, which can be considered as synthetic equivalents of the high energy and difficult to tame alkenyl radicals. The process, which can often be accomplished one-pot, could be extended in one case to an α,ß-unsaturated ester.

A Convergent Approach to 1,3-Dithiolan-2-ones and an Unexpected Synthesis of Lactones.

A convergent route to 1,3-dithiolan-2-ones based on the radical addition of xanthates to allylic acetates is described. The process is modular, uses inexpensive starting materials and reagents, and is atom economical, since both sulfur atoms of the xanthate end up in the products. With adducts derived from xanthates bearing an ester group, an unexpected transformation leading to lactones was uncovered.

Modular Routes to 1,3-Dithian-2-ones and 1,2-Dithiolanes.

Convergent routes to 1,3-dithian-2-ones based on the radical addition of xanthates to alkenes possessing a suitably located (latent) leaving group are described. These can be converted into 1,2-dithiolanes by base-mediated hydrolysis and oxidation. A broad variety of functional groups can be introduced, and the process is modular, uses inexpensive starting materials and reagents, and is atom economical, because both sulfur atoms of the xanthate end up in the products.

A Route to 5,5-Dithiospiroketals and to Long-Chain Monomers from the Biomass.

5,5-Dithiospiroketals are prepared by a double radical addition of α,α'-bisxanthyl acetone to an alkene followed by ionic or thermal cleavage of the xanthate groups and acid-catalyzed ring closure. A modification employs α-chloro-α'-xanthyl acetone to give unsymmetrical derivatives. Reductive removal of the sulfur atoms with Raney nickel furnishes long-chain α,ω-diacids, diols, and diamines. Using biosourced alkenes, monomers and polymers can be obtained where essentially all the carbons are derived from the biomass.

A Modular Access to 1,2- and 1,3-Disubstituted Cyclobutylboronic Esters by Consecutive Radical Additions.

A modular approach to substituted cyclobutylboronic esters is described. It proceeds by successive intermolecular radical additions of xanthates to pinacolato 1-cyclobutenylboronate and to pinacolato bicyclo[1.1.0]but-1-ylboronate. Success hinges on tuning the stability of the α-boryl radical by exploiting the stabilizing influence of the trivalent boronic ester and the slightly destabilizing cyclobutane, which increases the σ-character of the radical. Reductive removal of the xanthate group finally provides a range of 1,2- and 1,3-disubstituted cyclobutylboronic esters. The contrast with cyclopropylboronic esters is striking, since the strong destabilization by the highly strained cyclopropane ring allows the first radical addition to take place but not the second. Furthermore, the first adducts are geminal xanthyl boronic esters that can be converted into cyclobutanones. This chemistry furnishes cyclobutylboronic esters that would be quite difficult to obtain otherwise and thus complements existing methods.

A Convergent, Stereoselective Route to Trisubstituted Alkenyl Boronates.

A modular, stereoselective route to trisubstituted (Z)-alkenyl (MIDA)boronates is described, consisting of the radical addition-fragmentation of dithiocarbonates to 2-(MIDA)boronyl-3-(2'-fluoro-pyridyl-6'-oxy)-alkenes. The bulky (MIDA)boronate ensures a highly stereoselective fragmentation that is enhanced by the poor stabilization of the radical adjacent to the tetravalent boron atom. The vinyl boronate precursors are prepared from propargyl alcohols by copper-catalyzed regioselective protoboration of their fluoropyridoxy derivatives, with the fluoropyridine acting as an internal directing group.

Dielectric spectroscopy of melt-extruded polypropylene and as-grown carbon nanofiber composites.

In this work, different weight contents of as-grown carbon nanofibers (CNFs), produced by chemical vapor deposition, were melt-extruded with polypropylene (PP) and their morphologic, structure and dielectric properties examined. The morphologic analysis reveals that the CNFs are randomly distributed in the form of agglomerates within the PP matrix, whereas the structural results depicted by Raman analysis suggest that the degree of disorder of the as-received CNFs was not affected in the PP/CNF composites. The AC conductivity of PP/CNF composites at room temperature evidenced an insulator-conductor transition in the vicinity of 2 wt.%, corresponding to a remarkable rise of the dielectric permittivity up to [Formula: see text] 12 at 400 Hz, with respect to the neat PP ([Formula: see text] 2.5). Accordingly, the AC conductivity and dielectric permittivity of PP/CNF 2 wt.% composites were evaluated by using power laws and discussed in the framework of the intercluster polarization model. Finally, the complex impedance and Nyquist plots of the PP/CNF composites are analyzed by using equivalent circuit models, consisting of a constant phase element (CPE). The analysis gathered in here aims at contributing to the better understanding of the enhanced dielectric properties of low-conducting polymer composites filled with carbon nanofibers.

Modular Approach to Substituted Pyridoazepinones.

Pyridoazepinones are potentially interesting structures, yet they are still underexploited in the medicinal chemistry field and hard to obtain synthetically. We present a general and flexible synthetic route to substituted pyridoazepinones, enabled by the xanthate addition-transfer process, which furnishes the target molecules from readily available starting materials in generally good yields. The method shows good functional group tolerance and allows the preparation of pyridoazepinone scaffolds on gram scale.