Hydrazone Activation in the Aminocatalytic Cascade Reaction for the Synthesis of Tetrahydroindolizines.

In this Letter, we demonstrate the usefulness of hydrazone activation for the synthesis of biologically relevant tetrahydroindolizines. A pyrrol-derived hydrazone bearing a Michael acceptor moiety in the N-alkyl side chain has been designed with the aim of participating in the aminocatalytic cascade reaction leading to the annulation of the new six-membered heterocyclic scaffold. The application of (S)-(-)-α,α-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether as the aminocatalyst allows for the iminium ion-enamine-mediated cascade to proceed in a fully stereoselective manner.

Dearomative, aminocatalytic formal normal-electron-demand aza-Diels-Alder cycloaddition in the synthesis of tetrahydrofuropyridines.

In the manuscript the application of dearomative formal normal-electron-demand aza-Diels-Alder cycloaddition in the synthesis of tetrahydrofuropyridines is described. The developed approach utilizes aminocatalytic activation of 2-alkyl-3-furfurals that proceeds via formation of the dearomatized dienamine intermediate. Initially obtained cycloadducts have been subjected to subsequent transformations providing access to tetrahydrofuropyridines or functionalized cinnamates. The mechanism of the process has been confirmed by DFT calculations.

Pentaenolate activation in the organocatalytic allylic alkylation of indene-2-carbaldehydes.

In this manuscript, the application of pentaenolate intermediates in the allylic alkylation of indene-2-carbaldehydes with Morita-Baylis-Hillman (MBH) carbonates is described. The reaction has been carried out in a highly enantio- and diastereoselective manner due to the use of a chiral tertiary amine as a nucleophilic catalyst. The developed reactivity constitutes the first application of organocatalytic pentaenolate activation in asymmetric synthesis, expanding the arsenal of catalytic methods.

Asymmetric Organocatalysis in the Remote (3 + 2)-Cycloaddition to 4-(Alk-1-en-1-yl)-3-cyanocoumarins.

The application of organocatalytic bifunctional activation in the remote (3 + 2)-cycloaddition between 4-(alk-1-en-1-yl)-3-cyanocoumarins and imines derived from salicylaldehyde is demonstrated. Products, bearing two biologically relevant units, have been obtained with good chemical and stereochemical efficiency. The stereochemical outcome of the process results from the application of a quinine-derived catalyst. Selected transformations of the cycloadducts leading to further chemical diversity have been demonstrated.

Synthesis of cyclopent-1-enecarbonitriles via a tandem Giese/HWE reaction initiated by visible light.

In the manuscript, a novel method for the preparation of cyclopent-1-enecarbonitriles via tandem Giese/HWE reaction initiated by visible light in the presence of fac-Ir(ppy)3 as a photocatyst has been described. The cascade reactivity combining radical and polar processes has proven applicable for a wide range of N-(acyloxy)phthalimides (which serve as precursors of the corresponding radicals) as well as diethyl (E)-(1-cyano-2-arylvinyl)phosphonates. The key parameters responsible for the success of the described strategy are: visible light, 1 mol% of photoredox catalyst, base, anhydrous solvent and inert atmosphere. The reaction results in new sp3-sp3 and sp2-sp2 carbon-carbon bonds formation under mild conditions.

Organocatalytic Asymmetric Approach to γ,δ-Functionalization of 3-Cyano-4-styrylcoumarins via Bifunctional Catalysis.

A novel organocatalytic reaction cascade between 3-cyano-4-styrylcoumarins and 2-mercaptoacetophenones is described. It is based on stereocontrolled functionalization of cyanocoumarins proceeding in a sequence of thia-Michael/aldol/annulation reactions. This highly diastereo- and enantioselective reaction is realized by employing enantioselective bifunctional catalysis and exhibits a broad substrate scope and excellent functional group tolerance. The synthetic application involves the transformation of the imidoester group, thus opening access to biologically relevant coumarin and δ-lactone-fused products.

Classification of Polish Natural Bee Honeys Based on Their Chemical Composition.

The targeted quantitative NMR (qNMR) approach is a powerful analytical tool, which can be applied to classify and/or determine the authenticity of honey samples. In our study, this technique was used to determine the chemical profiles of different types of Polish honey samples, featured by variable contents of main sugars, free amino acids, and 5-(hydroxymethyl)furfural. One-way analysis of variance (ANOVA) was performed on concentrations of selected compounds to determine significant differences in their levels between all types of honey. For pattern recognition, principal component analysis (PCA) was conducted and good separations between all honey samples were obtained. The results of present studies allow the differentiation of honey samples based on the content of sucrose, glucose, and fructose, as well as amino acids such as tyrosine, phenylalanine, proline, and alanine. Our results indicated that the combination of qNMR with chemometric analysis may serve as a supplementary tool in specifying honeys.

5-Substituted-furan-2(3H)-ones in [8 + 2]-Cycloaddition with 8,8-Dicyanoheptafulvene.

This study demonstrates the use of organocatalytic Brønsted base activation of 5-substituted-furan-2(3H)-ones to generate 2π-components for the diastereoselective [8 + 2]-cycloaddition involving 8,8-dicyanoheptafulvene as an 8π-component. The use of dienolates in a higher-order cycloaddition reaction leads to the formation of biologically relevant polycyclic products bearing a γ-butyrolactone structural motif, thus broadening the synthetic potential of Brønsted base activated higher-order cycloadditions.

Dearomative Michael addition involving enals and 2-nitrobenzofurans realized under NHC-catalysis.

In this manuscript, the first enantioselective dearomative Michael addition between α,ß-unsaturated aldehydes and 2-nitrobenzofurans realized under N-heterocyclic carbene activation has been described. The reaction proceeds via addition of homoenolate to Michael acceptors leading to the formation of biologically important heterocycles with high yields and stereoselectivities. Their functionalization potential has been confirmed in selected, diastereoselective transformations.

Differentiating Catalysis in the Dearomative [4 + 2]-Cycloaddition Involving Enals and Heteroaromatic Aldehydes.

In this paper, the application of differentiating catalysis in the [4 + 2]-cycloaddition between 2-alkyl-3-formylheteroarenes and α,ß-unsaturated aldehydes is described. Within the developed approach, the same aminocatalyst is employed for the independent activation of both starting materials, differentiating their properties via LUMO-lowering and HOMO-rising principles. By the combination of dearomative dienamine activation with iminium ion chemistry high enantio- and diastereoselectivity of the doubly asymmetric process was accomplished. Selected transformations of products were also demonstrated.

Asymmetric Dearomative (3+2)-Cycloaddition Involving Nitro-Substituted Benzoheteroarenes under H-Bonding Catalysis.

In our studies, the organocatalytic 1,3-dipolar cycloaddition between 2-nitrobenzofurans or 2-nitrobenzothiophene and N-2,2,2-trifluoroethyl-substituted isatin imines has been developed. The reaction has been realized by employing bifunctional organocatalysis, with the use of squaramide derivative being crucial for the stereochemical efficiency of the process. The usefulness of the cycloadducts obtained has been confirmed in selected transformations, including aromative and non-aromative removal of the nitro group.

Solid-Phase Synthesis of an Insect Pyrokinin Analog Incorporating an Imidazoline Ring as Isosteric Replacement of a trans Peptide Bond.

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).

The First Application of 1H NMR Spectroscopy for the Assessment of the Authenticity of Perfumes.

The manufacture of counterfeit goods is one of the world's largest underground businesses and is rapidly growing. Counterfeits can lead not only to the loss of profit for honest producers but also have a negative impact on consumers who pay excessive prices for poor quality goods that may result in health or safety problems. The perfume industry is constantly vulnerable to counterfeits, particularly in the fast developing market of "smell-alike" designer-inspired perfumes because these prompt the identification of the methods that classify their quality. In this paper, the application of proton nuclear magnetic resonance (1H NMR) spectroscopy is employed for the first time to authenticate perfumery products. The molecular composition of several types of authentic brand fragrances for women was compared with cheap inspired equivalents and fakes. Our approach offers the prospect of a fast and simple method for detecting counterfeit perfumes using 1H NMR spectroscopy.

Vinylogous hydrazone strategy for the organocatalytic alkylation of heteroaromatic derivatives.

A new umpolung approach for the asymmetric Friedel-Crafts-type alkylation of electron-poor heteroaromatic systems has been developed. It is based on the vinylogous reactivity of hydrazones derived from heteroaromatic aldehydes. The donating effect of the hydrazone moiety can be efficiently transferred over the heteroaromatic system activating it towards an asymmetric Friedel-Crafts reaction with α,ß-unsaturated aldehydes realized under aminocatalytic conditions. Excellent enantioselectivities have been obtained owing to the application of a MacMillan imidazolidinone catalyst. Unmasking of the hydrazone moiety has also been realized resulting in the development of a unique strategy for the asymmetric functionalization of electron-poor heteroaromatic systems.

1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii.

Congenital and acquired toxoplasmosis caused by the food- and water-born parasite Toxoplasma gondii (T. gondii) is one of the most prevalent zoonotic infection of global importance. T. gondii is an obligate intracellular parasite with limited capacity for extracellular survival, thus a successful, efficient and robust host cell invasion process is crucial for its survival, proliferation and transmission. In this study, we screened a series of novel 1,3,4-thiadiazole-2-halophenylamines functionalized at the C5 position with the imidazole ring (1b-12b) for their effects on T. gondii host cell invasion and proliferation. To achieve this goal, these compounds were initially subjected to in vitro assays to assess their cytotoxicity on human fibroblasts and then antiparasitic efficacy. Results showed that all of them compare favorably to control drugs sulfadiazine and trimethoprim in terms of T. gondii growth inhibition (IC50) and selectivity toward the parasite, expressed as selectivity index (SI). Subsequently, the most potent of them with meta-fluoro 2b, meta-chloro 5b, meta-bromo 8b, meta-iodo 11b and para-iodo 12b substitution were tested for their efficacy in inhibition of tachyzoites invasion and subsequent proliferation by direct action on established intracellular infection. All the compounds significantly inhibited the parasite invasion and intracellular proliferation via direct action on both tachyzoites and parasitophorous vacuoles formation. The most effective was para-iodo derivative 12b that caused reduction in the percentage of infected host cells by 44% and number of tachyzoites per vacuole by 93% compared to non-treated host cells. Collectively, these studies indicate that 1,3,4-thiadiazoles 1b-12b, especially 12b with IC50 of 4.70 µg/mL and SI of 20.89, could be considered as early hit compounds for future design and synthesis of anti-Toxoplasma agents that effectively and selectively block the invasion and subsequent proliferation of T. gondii into host cells.

Hydroxyl-group-activated azomethine ylides in organocatalytic H-bond-assisted 1,3-dipolar cycloadditions and beyond.

1,3-Dipolar cycloaddition constitutes a powerful means for the synthesis of five-membered heterocycles. Recently, the potential of this field of chemistry has been expanded by the employment of organocatalytic activation strategies. One group of substrates, namely imines derived from salicylaldehydes, is particularly useful. Additional activation via intramolecular H-bonding interactions offered by the presence of an ortho-hydroxyl phenolic group in their structure results in increased reactivity of these reactants. Furthermore, it can be utilized in subsequent reactions creating chemical and stereochemical diversity. This minireview provides a summary of the recent progress in this field of organocatalysis and indicates other important applications of hydroxyl-group-activated azomethine ylides in asymmetric organocatalysis.

The Application of NMR Spectroscopy and Chemometrics in Authentication of Spices.

Spices and herbs are among the most commonly adulterated food types. This is because spices are widely used to process food. Spices not only enhance the flavor and taste of food, but they are also sources of numerous bioactive compounds that are significantly beneficial for health. The healing effects of spices are connected with their antimicrobial, anti-inflammatory and carminative properties. However, regular consumption of adulterated spices may cause fatal damage to our system because adulterants in most cases are unhealthy. For that reason, the appropriate analytical methods are necessary for quality assurance and to ensure the authenticity of spices. Spectroscopic methods are gaining interest as they are fast, require little or no sample preparation, and provide rich structural information. This review provides an overview of the application of NMR spectroscopy combined with chemometric analysis to determine the quality and adulteration of spices.

Enantioselective H-bond-directed vinylogous iminium ion strategy for the functionalization of vinyl-substituted heteroaryl aldehydes.

In this work the first H-bond-directed vinylogous iminium ion strategy has been developed as a convenient strategy for the γ,δ-functionalization of vinyl-substituted heteroaromatic aldehydes. Their reaction with α-mercaptoketones proceeds in a cascade manner involving 1,6-addition followed by intramolecular aldol reaction. Excellent stereoselectivities have been obtained as a result of the H-bond interactions controlling the outcome of the cyclization step. The application of the strategy for the synthesis of tricyclic compounds bearing furan, tetrahydrothiophene and dihydropyran moieties has also been demonstrated.

Visible-light synthesis of 4-substituted-chroman-2-ones and 2-substituted-chroman-4-ones via doubly decarboxylative Giese reaction.

Doubly decarboxylative, photoredox synthesis of 4-substituted-chroman-2-ones and 2-substituted-chroman-4-ones is described. The reaction involves two independent decarboxylation processes: the first one initiating the cycle and the second completing the process. Visible light, photoredox catalyst, base, anhydrous solvent and inert atmosphere constitute the key parameters for the success of the developed transformation. The protocol proved applicable for coumarin-3-carboxylic acids and chromone-3-carboxylic acids as well as N-(acyloxy)phthalimide which served as precursors of the corresponding alkyl radicals.

Asymmetric vinylogous Michael addition of 5-substituted-furan-2(3H)-ones to an α,ß-unsaturated-γ-lactam.

The manuscript describes an utilization of 5-substituted-furan-2(3H)-ones as pronucleophiles in an asymmetric vinylogous Michael addition to an α,ß-unsaturated-γ-lactam, thus leading to hybrid molecules possessing γ-lactam and butenolide structural motifs. The transformation utilizes two potentially vinylogous pronucleophiles and has been realized by simultaneous activation of both substrates by a bifunctional organocatalyst derived from a cinchona alkaloid. Reaction occurs in a highly enantio- and diastereoselective manner and the synthetic potential of the target products has been confirmed in stereoselective transformations.