Cannabichromene (CBC) Shows Matrix-Dependent Thermal Configurational Stability.

The optical purity of cannabichromene (CBC, ) is affected by the matrix in which it is generated by thermolysis from its native carboxylated form (cannabichromenic acid, CBCA, ). Thus, thermolysis at 130 °C caused a marked decrease of the enantiomeric excess (ee), while, under the same conditions, only a modest decrease of optical purity was observed when thermolysis was carried out . To rationalize these puzzling observations, the kinetics of thermal (100 °C) racemization of enantiopure cannabichromene () was evaluated by enantioselective ultrahigh performance liquid chromatography in solvents (decalin and isopropyl alcohol, neat and acidified with TFA) and surfaces (native and silanized borosilicate glass) of complementary polarity.

Design, Synthesis, and Applications of Bis-Amido HPLC Pirkle-Type Chiral Stationary Phases.

Two different types of chiral stationary phases, based on Pirkle's design, were created by attaching chiral selectors to 3-mercapto silica gel. To prepare the enantiomeric selectors, 3,5-dinitrobenzoyl and naphthyl groups were sequentially added to a chiral 1,2-diaminocyclohexane core. The chiral selectors demonstrated enantioselectivity towards ibuprofen enantiomers in solution, as confirmed by H NMR spectroscopy, and in initial HPLC testing, the enantiomeric selectors showed enantioselectivity for selected racemic solutes (viz.

4-(3-Phenylsulfonylindol-2-yl)-1-(pyridin-2-yl)piperazinyl-methanones as Potent Inhibitors of both SARS-CoV-2 and HCoV-OC43 Viruses.

SARS-CoV-2 and HCoV-OC43 belong to the same β genus of the Coronaviridae family. SARS-CoV-2 was responsible for the recent COVID-19 pandemic, and HCoV-OC43 is the etiological agent of mild upper respiratory tract infections. SARS-COV-2 and HCoV-OC43 co-infections were found in children with respiratory symptoms during the COVID-19 pandemic.

Enantioselective high-performance liquid chromatography combined with spectroscopic methods and theoretical calculations: A valid strategy to determine the absolute configuration of eugenol derivatives.

The absolute configuration of three chiral eugenol derivatives was assigned by a multi-step methodology based on enantioselective HPLC combined with spectroscopic and theoretical calculations. Milligram amounts of enantiopure forms used for stereochemical characterization were isolated by HPLC on the immobilized amylose-based chiral stationary phase Chiralpak IG using normal phase elution conditions. The absolute configuration was indirectly determined for one of the three compounds by H NMR via methoxy-α-trifluoromethyl-α-phenylacetic acid derivatization (Mosher's acid).

Assessing the performance of new chromatographic technologies for the separation of peptide epimeric impurities: the case of Icatibant.

The biopharmaceutical industry faces the challenge of efficiently characterising impurity profiles of therapeutical peptides, also due to their complex polar and ionisable attributes. This research explores the potential of advanced chromatographic techniques to address this challenge. The study compares dynamic electrostatic repulsion reversed phase (d-ERRP) to its counterparts (static ERRP and ion pair reversed phase IP-RP) in analysing Icatibant and its elusive epimeric impurity, [L-Arg]-Icatibant and highlights its exceptional capabilities in generating symmetric peaks, mitigating the common tailing phenomenon, and serving as a steadfast guardian of column longevity.

Chiral distinction between hydroxychloroquine enantiomers in binding to angiotensin-converting enzyme 2, the forward receptor of SARS-CoV-2.

Soon after the outset of the Coronavirus Disease 2019 (COVID-19) pandemic (March-April 2020), formulations of the old antimalarial racemic drug hydroxychloroquine (HCQ) sulfate were authorized by the U.S. Food and Drug Administration (FDA) for emergency treatment of hospitalized patients with COVID-19.

Theoretically Predicted and Experimentally Detected Chirality of Dibenzocyclooctynes and Their Triazole Adducts with Azides.

Dibenzocyclooctynes have emerged as promising scaffolds for bioorthogonal ligation. An important structural aspect that has not been addressed so far relates to their chirality. Herein, we explore, by theoretical and experimental methods, this structural aspect that has been neglected so far.

Understanding the Transition from High-Selective to High-Efficient Chiral Separations by Changing the Organic Modifier with Zwitterionic-Teicoplanin Chiral Stationary Phase.

The retention behavior of small molecules and N-protected amino acids on a zwitterionic teicoplanin chiral stationary phase (CSP), prepared on superficially porous particles (SPPs) of 2.0 μm particle diameter, has shown that efficiency and enantioselectivity, and so enantioresolution, dramatically change depending on the employed organic modifier. In particular, it was found that while methanol permits the boost of enantioselectivity and resolution of the amino acids, at the cost of efficiency, acetonitrile allows for the ability to reach extraordinary efficiency even at high flow rates (with reduced plate height <2 and up to 300,000 plates/m at the optimum flow rate).

Natural Cannabichromene (CBC) Shows Distinct Scalemicity Grades and Enantiomeric Dominance in Strains.

Cannabichromene (CBC, ) occurs in Cannabis () as a scalemate having a composition that is strain-dependent in terms of both enantiomeric excess and enantiomeric dominance. In the present work, the chirality of CBC (), a noncrystalline compound, was shown not to be significantly affected by standard conditions of isolation and purification, and enantiomeric self-disproportionation effects were minimized by carrying out the chiral analysis on crude fractions rather than on purified products. A genetic basis for the different enantiomeric state of CBC in Cannabis therefore seems to exist, implying that the chirality status of natural CBC () in the plant is associated with the differential expression of CBCA-synthase isoforms and/or of associated directing proteins with antipodal enantiospecificity.

Highly Efficient and Mild Gold (I) Catalyzed Synthesis of 3,8-Diarylidene-2,7-dioxaspiro[4.4]nonane-1,6-diones.

The gold-catalyzed cyclization of 2,2-bis(3-arylprop-2-yn1-yl)malonic acid has been proposed as an efficient approach to substituted 3,8-dibenzyl-2,7-dioxaspiro[4.4]nonane-1,6-diones. The reaction proceeds smoothly in mild reaction conditions to give the desired products in quantitative yields in the presence of variously substituted starting materials.

Boosting the enantioresolution of zwitterionic-teicoplanin chiral stationary phases by moving to wide-pore core-shell particles.

A novel zwitterionic-teicoplanin chiral stationary phase (CSP), based on superficially porous particles (SPPs) of 2.7 µm particle diameter and 160 Å pore size, has been prepared and evaluated towards the enantioseparation of important classes of compounds, including chiral drugs, pesticides, and N-derivatized amino acids. The comparison with two analogous CSPs prepared on SPPs with 2.

Preparation of a high-density vinyl silica gel to anchor cysteine via photo-click reaction and its applications in hydrophilic interaction chromatography.

Modification of surface silanols is a topic of interest in the preparation of organo-functionalized silica particles. Herein, two novel contributions, mainly focused on separation science, were presented: i) the horizontal polymerization on silica surface by using the vinyl-triacetoxy silane and ii) a preparation of cysteine-based stationary phase via photo-click thiol-ene coupling. In the first derivatization step, the vinyl-triacetoxy silane was employed instead of conventional trichloro vinyl one.

One-pot synthesis of dihydroquinolones by sequential reactions of -aminobenzyl alcohol derivatives with Meldrum's acids.

The functionalized 3,4-dihydroquinolin-2-one nucleus has been assembled in good to high yields through the sequential reaction of readily available -Ts--aminobenzyl alcohols with 5-substituted Meldrum's acid derivatives under mild basic conditions. Highly diastereoselective synthesis of 3-substituted-4-phenyl-1-tosyl-3,4-dihydroquinolin-2(1)-ones was accomplished from -(2-(hydroxy(phenyl)methyl)phenyl)-4-methylbenzenesulfonamide under the same reaction conditions. Regarding the reaction mechanism, we hypothesized that the formation of dihydroquinolones proceeds through the generation of aza--QMs followed by conjugate addition of enolate/cyclization/elimination of acetone and CO.

Δ--Tetrahydrocannabinol: Natural Occurrence, Chirality, and Pharmacology.

The -stereoisomers of Δ-THC [(-)- and (+)-] were identified and quantified in a series of low-THC-containing varieties of registered in Europe as fiber hemp and in research accessions of cannabis. While Δ--THC () occurs in cannabis fiber hemp in the concentration range of (-)-Δ--THC [(-)-], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ--THC () is scalemic (ca.

Expanding the Use of Dynamic Electrostatic Repulsion Reversed-Phase Chromatography: An Effective Elution Mode for Peptides Control and Analysis.

Bioactive peptides are increasingly used in clinical practice. Reversed-phase chromatography using formic or trifluoroacetic acid in the mobile phase is the most widely used technique for their analytical control. However, sometimes it does not prove sufficient to solve challenging chromatographic problems.

Synthesis of 4-Substituted-1,2-Dihydroquinolines by Means of Gold-Catalyzed Intramolecular Hydroarylation Reaction of -Ethoxycarbonyl--Propargylanilines.

An alternative Au(I)-catalyzed synthetic route to functionalized 1,2-dihydroquinolines is reported. This novel approach is based on the use of -ethoxycarbonyl protected--propargylanilines as building blocks that rapidly undergo the IMHA reaction affording the 6- cyclization product in good to high yields. In the presence of -ethoxycarbonyl--propargyl-substituted anilines, the regiodivergent cyclization at the -/-position is achieved by the means of catalyst fine tuning.

Palladium-catalyzed Tsuji-Trost-type reaction of benzofuran-2-ylmethyl acetates with nucleophiles.

The palladium-catalyzed benzylic-like nucleophilic substitution of benzofuran-2-ylmethyl acetate with N, S, O and C soft nucleophiles has been investigated. The success of the reaction is dramatically influenced by the choice of catalytic system: with nitrogen based nucleophiles the reaction works well with Pd(dba)/dppf, while with sulfur, oxygen and carbo-nucleophiles [Pd(η-CH)Cl]/XPhos is more efficient. The regiochemical outcome shows that the nucleophilic substitution occurs only on the benzylic position of the η-(benzofuryl)methyl complex.

Mass transfer kinetics on modern Whelk-O1 chiral stationary phases made on fully- and superficially-porous particles.

In this work, a detailed study of mass transfer properties of trans-stilbene oxide (TSO) enantiomers on two Whelk-O1 chiral stationary phases (CSPs) has been performed. The CSPs were prepared by using both fully-porous silica particles of 2.5 μm particle diameter and superficially-porous ones of 2.

High-throughput enantioseparation of Nα-fluorenylmethoxycarbonyl proteinogenic amino acids through fast chiral chromatography on zwitterionic-teicoplanin stationary phases.

In this study, 31 racemates of Nα-FMOC (fluorenylmethoxycarbonyl) amino acids (AAs) with different chemico-physical characteristics (neutral nonpolar, neutral polar, acidic and basic) have been successfully resolved in fast enantioselective chromatography on recently-developed zwitterionic-teicoplanin chiral stationary phases (CSPs). The CSPs were prepared by covalently bonding the teicoplanin selector on fully-porous particles of narrow dispersion particle-size distribution (particle diameter 1.9 µm) and superficially-porous particles (2.

L. Inflorescences from Monoecious Cultivars Grown in Central Italy: An Untargeted Chemical Characterization from Early Flowering to Ripening.

The chemical composition of the inflorescences from four L. monoecious cultivars (Ferimon, Uso-31, Felina 32 and Fedora 17), recently introduced in the Lazio Region, was monitored over the season from June to September giving indications on their sensorial, pharmaceutical/nutraceutical proprieties. Both untargeted (NMR) and targeted (GC/MS, UHPLC, HPLC-PDA/FD and spectrophotometry) analyses were carried out to identify and quantify compounds of different classes (sugars, organic acids, amino acids, cannabinoids, terpenoids, phenols, tannins, flavonoids and biogenic amines).

Boosting basic-peptide separation through dynamic electrostatic-repulsion reversed-phase (d-ERRP) liquid chromatography.

The application of a novel chromatographic approach to therapeutic peptides bearing basic amino acids in their structure allowed unprecedented resolution of their related impurities (including epimeric isobaric ones), resulting in a superior analytical tool for the evaluation of the quality of these drugs in the market.

Investigation of mass transfer properties and kinetic performance of high-efficiency columns packed with C sub-2 μm fully and superficially porous particles.

Three columns packed with 2.0 μm superficially porous particles, 1.7 μm fully porous particles, and monodisperse 1.