Unraveling the Role of Structural Topology on Chirality Transfer and Chiroptical Properties in Chiral Germanium Iodides.

Chiral hybrid organic-inorganic metal halides are highly promising chiroptoelectronic materials with potential applications in several fields, such as circularly polarized photodetectors, second-order nonlinear optics, and spin-selective devices. However, the ability of manipulating the chiroptical response and the chirality transfer from the organic ligands require one to shed light on structure-property correlations. Herein, we devised and prepared two novel Ge-based chiral hybrid organic-inorganic metal halides showing a different structural topology, namely, a 1D and a 2D arrangement, but composed of the same chemical building blocks: (/-ClMBA)GeI and (/-ClMBA)GeI.

Easy and Accessible Synthesis of Cannabinoids from CBD.

Cannabidiol (CBD), a prominent phytocannabinoid found in various chemotypes, is under extensive investigation for its therapeutic potential. Moreover, because it is nonpsychoactive, it can also be utilized as a functional ingredient in foods and supplements in certain countries, depending on its legal status. From a chemical reactivity point of view, CBD can undergo conversion into different structurally related compounds both during storage and after the consumption of CBD-based products.

Ligand-Induced Chirality in ClMBA SnI 2D Perovskite.

Chiral perovskites possess a huge applicative potential in several areas of optoelectronics and spintronics. The development of novel lead-free perovskites with tunable properties is a key topic of current research. Herein, we report a novel lead-free chiral perovskite, namely (R/S-)ClMBA SnI (ClMBA=1-(4-chlorophenyl)ethanamine) and the corresponding racemic system.

A New Benzothiazolthiazolidine Derivative, 11726172, Is Active , , and against Nonreplicating Cells of Mycobacterium tuberculosis.

Tuberculosis (TB) still poses a global menace as one of the deadliest infectious diseases. A quarter of the human population is indeed latently infected with Mycobacterium tuberculosis. People with latent infection have a 5 to 10% lifetime risk of becoming ill with TB, representing a reservoir for TB active infection.

Oxo-Rhenium-Mediated Allylation of Furanoside Derivatives: A Computational Study on the Mechanism and the Stereoselectivity.

Properly substituted tetrahydrofuran (THF) rings are important building blocks in the synthesis of many natural metabolites. Having reliable procedures to control the stereoselectivity at the THF core while decorating it with different substituents is a fundamental requirement to achieve and fulfill the complexity of nature. We recently reported a new chemical approach to control the stereochemistry in the alkylation and arylation of furanoside derivatives by using a rhenium(V) complex to form an intermediate oxo-carbenium species able to react with proper soft nucleophiles.

Photochemistry of Cannabidiol (CBD) Revised. A Combined Preparative and Spectrometric Investigation.

Cannabis is a plant with an astonishing ability to biosynthesize cannabinoids, and more than 100 molecules belonging to this class have been isolated. Among them in recent years cannabidiol (CBD) has received the interest of pharmacology as the major nonpsychotropic cannabinoid with many potential clinical applications. Although the reactivity of CBD has been widely investigated, only little attention has been given to the possible photodegradation of this cannabinoid, and the data available in the literature are outdated and, in some cases, conflicting.

Highly Stereoselective Glycosylation Reactions of Furanoside Derivatives via Rhenium (V) Catalysis.

A novel approach for the formation of anomeric carbon-functionalized furanoside systems was accomplished through the employment of an oxo-rhenium catalyst. The transformation boasts a broad range of nucleophiles including allylsilanes, enol ethers, and aromatics in addition to sulfur, nitrogen, and hydride donors, able to react with an oxocarbenium ion intermediate derived from furanosidic structures. The excellent stereoselectivities observed followed the Woerpel model, ultimately providing 1,3--1,4- systems.

Shedding X-ray Light on the Role of Magnesium in the Activity of Salicylate Synthase (MbtI) for Drug Design.

The Mg-dependent salicylate synthase (MbtI) is a key enzyme involved in the biosynthesis of siderophores. Because iron is essential for the survival and pathogenicity of the microorganism, this protein constitutes an attractive target for antitubercular therapy, also considering the absence of homologous enzymes in mammals. An extension of the structure-activity relationships of our furan-based candidates allowed us to disclose the most potent competitive inhibitor known to date (, = 4 μM), which also proved effective on mycobacterial cultures.

Chemical, Metabolic, and Cellular Characterization of a FtsZ Inhibitor Effective Against .

There is an urgent need for new antimicrobials to treat the opportunistic Gram-negative , which represents a problematic challenge for cystic fibrosis patients. Recently, a benzothiadiazole derivative, C109, was shown to be effective against the infections caused by and other Gram-negative and-positive bacteria. C109 has a promising cellular target, the cell division protein FtsZ, and a recently developed PEGylated formulation make it an attractive molecule to counteract infections.

Direct meta-C-H Perfluoroalkenylation of Arenes Enabled by a Cleavable Pyrimidine-Based Template.

The development of efficient and mild methods for the synthesis of organofluorine compounds is of foremost interest in various fields of chemistry. A direct pyrimidine-based selective meta-C-H perfluoroalkenylation of arenes involving several commercially available perfluoroolefins is described. The synthetic versatility of the protocol is demonstrated by an extensive substrate scope including different benzylsulfonyl, alkylarene and phenylacetic acid scaffolds.

Expedient Access to 2-Benzazepines by Palladium-Catalyzed C-H Activation: Identification of a Unique Hsp90 Inhibitor Scaffold.

Bioactive 2-benzazepines were accessed in an atom- and step-economical manner through a versatile palladium-catalyzed C-H activation strategy. The C-H arylation required low catalyst loading and a mild base, which was reflected by a broad scope and high functional-group tolerance. The benzotriazolodiazepinones were identified as new heat shock protein 90 (Hsp90) inhibiting lead compounds, with considerable potential for anti-cancer applications.

Ene Reaction of Nitrosocarbonyl Mesitylene with the Cinnamyl Alcohol: Metabolic Activity and Apoptosis of the Synthetized 6-Chloropurine N,O-Nucleoside Analogues.

Nitrosocarbonyl mesitylene intermediate undergoes an ene reaction with cinnamyl alcohol affording the corresponding 5-hydroxy-isoxazolidine in fair yields. The synthesized 5-acetoxy-isoxazolidine serves as synthon for the preparation of 6-chloropurine N,O-nucleoside analogues, according to the Vorbrüggen reaction. The compounds were evaluated for their metabolic and apoptotic activity, and their structure-activity relationship is discussed.

Bifunctional Ligand Enables Efficient Gold-Catalyzed Hydroalkenylation of Propargylic Alcohol.

Using the previously designed biphenyl-2-ylphosphine ligand, featuring a remote tertiary amino group, the first gold-catalyzed intermolecular hydroalkenylation of alkynes has been developed. Synthetically valuable conjugated dienyl alcohols are formed in moderate to good yields. A range of alkenyltrifluoroborates are allowed as the alkenyl donor, and no erosion of alkene geometry and/or the propargylic configuration are detected.

Stereoselective preparation of key intermediates for the synthesis of iso-, neuro- and phyto-prostane family members: inaugural asymmetric synthesis of 17-E-dihomo- and 17-F-dihomo-isoprostanes.

A practical methodology for the synthesis of key intermediates for isoprostane, neuroprostane and dihomo-isoprostane preparation has been described. The key strategy involved a three stage C-12 stereocenter inversion of the configuration of a Corey lactone, commercially available in an enantiopure form. The key intermediate was then used to prepare 17-E2c-dihomo-isoprostane and 17-F2c-dihomo-isoprostane.

Alkynyl N-Nosylhydrazones: Easy Decomposition to Alknynl Diazomethanes and Application in Allene Synthesis.

The decomposition of N-tosylhydrazones is a safe and convenient method for the generation of donor carbenes. However, alkynyl carbenes cannot be isolated by this route because they readily undergo intramolecular cyclization to pyrazoles as soon as formed from alkynyl N-tosylhydrazones. Here, the use of alkynyl N-nosylhydrazones for the in situ generation of alkynyl carbenes and their coupling reaction with boronic acids under metal-free conditions is reported, giving rise to a wide array of di- and trisubstituted allenes.

DHA Reduces Oxidative Stress after Perinatal Asphyxia: A Study in Newborn Piglets.

Background: Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurological morbidity in infants and children. Oxidative stress due to free radical formation and the initiation of abnormal oxidative reactions appears to play a key role. Docosahexanoic acid (DHA), a main component of brain membrane phospholipids, may act as a neuroprotectant after hypoxia-ischemia by regulating multiple molecular pathways and gene expression.

DHA-derived oxylipins, neuroprostanes and protectins, differentially and dose-dependently modulate the inflammatory response in human macrophages: Putative mechanisms through PPAR activation.

Whereas the anti-inflammatory properties and mechanisms of action of long chain ω3 PUFAs have been abundantly investigated, research gaps remain regarding the respective contribution and mechanisms of action of their oxygenated metabolites collectively known as oxylipins. We conducted a dose-dependent and comparative study in human primary macrophages aiming to compare the anti-inflammatory activity of two types of DHA-derived oxylipins including the well-described protectins (NPD1 and PDX), formed through lipoxygenase pathway and the neuroprostanes (14-A- and 4-F-NeuroP) formed through free-radical mediated oxygenation and expected to be new anti-inflammatory mediators. Considering the potential ability of these DHA-derived oxylipins to bind PPARs and knowing the central role of these transcription factors in the regulation of macrophage inflammatory response, we performed transactivation assays to compare the ability of protectins and neuroprostanes to activate PPARs.

Two New Ergosterol Derivatives from the Basidiomycete Cortinarius glaucopus.

Two new sterols 1 and 2 and five known ones 3 - 7 were isolated for the first time from the fruiting bodies of Cortinarius glaucopus. Their structures were established by 1- and 2D-NMR spectra and HR-FABS-MS. The relative configuration of 1 was firmly determined by comparison of the observed H- H couplings and NOESY correlations, with those predicted for the computed geometries of the conformers.

A New Iridoid Dimer and Other Constituents from the Traditional Kurdish Plant Pterocephalus nestorianus Nábělek.

Accompanied by other rare compounds, a new iridoid dimer, named kurdnestorianoside (1), showing an unprecedented secologanol configuration, has been isolated for the first time from the Kurdish medicinal plant Pterocephalus nestorianus, which is used in Kurdistan for treating oral diseases and inflammation. The structure of 1 was established from 1D- and 2D-NMR spectroscopic data. Kaempferol 3-O-[3,6-di-O-(E)-p-coumaroyl]-β-d-glucopyranoside (7) showed a remarkable antiproliferative activity against several human tumor cell lines.

Fast low-pressurized microwave-assisted extraction of benzotriazole, benzothiazole and benezenesulfonamide compounds from soil samples.

Benzotriazoles (BTRs), benzothiazoles (BTs) and benzenesulfonamides (BSAs), compounds largely used in industrial and household applications, are ubiquitous emerging contaminants. In this work a novel, straightforward procedure for the simultaneous determination of two BTRs (1H-benzotriazole, 5-methyl-1H-benzotriazole), three BTs (benzothiazole, 2-hydroxybenzothiazole, 2-methylthiobenzothiazole) and two BSAs (benzenesulfonamide, toluenesulfonamide) in soil has been developed. The target analytes were extracted from soil by a single low-pressurized microwave-assisted extraction (MAE) cycle (120°C, 10min) and quantified by high-performance liquid chromatography with UV detection.

Neuroprostanes, produced by free-radical mediated peroxidation of DHA, inhibit the inflammatory response of human macrophages.

The anti-inflammatory properties of DHA have been largely demonstrated in vitro and in vivo but research gaps remain regarding the contribution of the oxygenated metabolites. Among them, we are focusing on prostaglandin-like molecules termed Neuroprostanes (NeuroPs) which are produced through free-radical-mediated peroxidation of DHA. We hypothesized that these specific molecules which are highly reactive and produced in abundance during oxidative stress and inflammation could contribute to the anti-inflammatory properties of DHA.

Competitive Gold-Promoted Meyer-Schuster and oxy-Cope Rearrangements of 3-Acyloxy-1,5-enynes: Selective Catalysis for the Synthesis of (+)-(S)-γ-Ionone and (-)-(2S,6 R)-cis-γ-Irone.

We report a simple, highly stereoselective synthesis of (+)-(S)-γ-ionone and (-)-(2S,6R)-cis-γ-irone, two characteristic and precious odorants; the latter compound is a constituent of the essential oil obtained from iris rhizomes. Of general interest in this approach are the photoisomerization of an endo trisubstituted cyclohexene double bond to an exo vinyl group and the installation of the enone side chain through a [(NHC)Au(I)]-catalyzed Meyer-Schuster-like rearrangement. This required a careful investigation of the mechanism of the gold-catalyzed reaction and a judicious selection of reaction conditions.

The Importance of the 5-Alkyl Substituent for the Violet Smell of Ionones: Synthesis of Racemic 5-Demethyl-α-ionone.

The synthesis and the odor tonalities of racemic 5-demethyl-α-ionone are described. This synthetic ionone derivative did not show the typical floral-woody violet smell of α-ionone, definitely proving the importance of a suitably sized and spatially oriented alkyl substituent at C(5) for stimulating olfactory receptors of ionones.

Thiophenecarboxamide Derivatives Activated by EthA Kill Mycobacterium tuberculosis by Inhibiting the CTP Synthetase PyrG.

To combat the emergence of drug-resistant strains of Mycobacterium tuberculosis, new antitubercular agents and novel drug targets are needed. Phenotypic screening of a library of 594 hit compounds uncovered two leads that were active against M. tuberculosis in its replicating, non-replicating, and intracellular states: compounds 7947882 (5-methyl-N-(4-nitrophenyl)thiophene-2-carboxamide) and 7904688 (3-phenyl-N-[(4-piperidin-1-ylphenyl)carbamothioyl]propanamide).