The enantioselective Povarov reaction is one of the most powerful synthetic strategy to synthesize chiral, highly functionalized 1,2,3,4‐tetrahydroquinolines. The present Minireview aims to collect ...the most significant successful examples of highly efficient enantioselective catalytic protocols for this reaction, since 2014. A comprehensive discussion of different catalytic strategies employed in recent years to realize the enantioselective Povarov reaction is provided; the use of chiral phosphoric acids, thio(urea) and proline derivatives, as well as transition metal complexes will be presented. Additionally, this Minireview critically discusses the intriguing and yet obscure mechanistic pathways of this well‐known reaction, the controversial dispute between a concerted or a polar two‐step process.
One of the best‐studied routes to prepare chiral tetrahydroquinolines is known as the enantioselective Povarov reaction. In this Minireview enantioselective Povarov reactions published since 2014 are presented, according to the chiral catalyst used, either an organocatalyst or a metal complex, and discussed. When possible, special attention has been given to the rationalization of the stereochemical outcome of the reaction, discussing transition states and catalytic cycles.
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•Ten enamine naphthoquinones were satisfactorily synthesized.•The antiproliferative activity were determined in four human cancer line cell.•Qualitative Structure/Biological Activity ...relationship was made.•Docking indicated that molecules inhibit topoisomerase and thymidylate synthase.
We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 μM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2–C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.
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•DFT calculations predict formation of carbonates from glycerol reacting with CO2.•Tertiary alkylamines may activate glycerol for reaction with CO2.•Intermolecular hydrogen bond ...increases glycerol nucleophilicity.•FTIR and 13C NMR and 1H–13C HMBC spectra suggest formation of organic carbonate.
Although CO2 capture by alkanolamine aqueous solutions is a well-established technology, it demands high energy penalties and water consumption. Therefore, the development of new methods for CO2 removal is still a challenge. Herein, we employed the Density Functional Theory (DFT) to explore the potential of different mixtures composed of glycerol and nitrogen-containing bases to capture CO2. By combining glycerol, CO2 and the bases, it was possible to show that aliphatic amines are able to form intermolecular hydrogen bonds with the primary hydroxyl groups of glycerol, increasing their nucleophilicity and assisting the reaction with CO2 to form glycerol carbonate as the most stable product. To confirm that glycerol carbonate would be experimentally obtained from the given mixture, we selected triethylamine (TEA) to assist glycerol (Gly) in its reaction with CO2. The resulting product was characterized by Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), 1D and 2D Nuclear Magnetic Resonance spectroscopy (1H and 13C NMR) and Thermogravimetric Analysis (TGA). The ATR-FTIR results showed that TEA is protonated after bubbling CO2 in the glycerol/TEA mixture, suggesting that the reaction with CO2 occurs after deprotonation of glycerol, forming organic carbonates, as also indicated in the NMR spectra. The combined theoretical and experimental results indicate that TEA is able to activate glycerol in its reaction with CO2 to form organic carbonates, being an alternative procedure for CO2 capture.
Molecules with the quinone structure containing nitrogen constitute one of the most interesting classes of compounds in organic chemistry because of their biological properties and their potential as ...intermediates in the synthesis of heterocycles. This work describes a clean, efficient and facile one-pot protocol for the synthesis of a series of new aminonaphthoquinones derived from 2-hydroxy-1,4-naphthoquinone (lawsone) by three-component Mannich reaction using catalytic amount of p-TsOH at room temperature. At the present work, we improved the yield and significantly reduced the reaction time for several Mannich reactions with different amine and aromatic aldehydes using a non-expensive, mild catalyst and suitable solvent.
A clean, efficient and facile one-pot protocol was developed for the synthesis of a series of new aminonaphthoquinones derived from 2-hydroxy-1,4-naphthoquinone (lawsone) by three-component Mannich reaction using catalytic amount of p-TsOH in CH3CN, at room temperature. At the present work, we improved the yield and significantly reduced the reaction time for several Mannich reactions with different amine and aromatic aldehydes using a non-expensive, mild catalyst and suitable solvent.
C-Glycosyl-flavonoids are phytochemical natural products that possess different biological applications. Several compounds from this class exhibit rotational isomerism, evidenced by NMR signal ...duplication. This phenomenon is usually associated with the restricted rotation of the C(sp3)–C(sp2) bond in the sugar-aglycone, however the reasons for its occurrence remain underexplored and demand further investigation. Herein, we conducted a DFT (B3LYP-D3/6-311++G(d,p)/IEFPCM) investigation to elucidate the origin of rotational isomerism in a diverse set of C-glycosyl-flavonoids, including isoschaftoside (1), schaftoside (2), vitexin (3), puerarin (4), and prunetin-8-C-glucoside (5), rationally chosen to understand the substituent effects in different positions in the flavonoid backbone. Our outcomes reveal that the rotation around the sugar-aglycone bond at the 8-C position of the flavonoid moiety has the most energetic barrier, although the value is not sufficient to induce NMR signal duplication (ΔG‡ = 14.5 ± 0.5 kcal mol−1). Only by simulating the solvent molecules explicitly, using a hybrid cluster-continuum model, we were able to identify the occurrence of rotational isomerism, revealing that the flavonoid–solvent interactions play an important role to the NMR signal duplication. The calculated rotational barriers range from 17.3 to 20.9 kcal mol−1, which is sufficient to cause bond hindrance rotation and identification of NMR double signals due to slow interconversion between the rotamers.
In the early 2000s, the first articles regarding the calculation of NMR parameters for natural products appeared in the literature. Since then, modelling 1H and 13C chemical shifts and spin–spin ...coupling constants for this class of compounds has experienced a remarkable increase in precision, accessibility, and application, leading to considerable advances in the field. More recently, significant contributions from several authors have led to continuous growth in this research field, updating and broadening the simulation of NMR parameters, in particular with the application of new techniques for data treatment. Nowadays, such studies are routinely found in the high impact literature. In this review, we intend to cover the general guidelines and the main advances in NMR calculations of natural products published since 2012. We intend to address the bottlenecks of quantum chemical calculations of NMR parameters, including mathematical definitions, updates, and a discussion of relevant examples, and to highlight novel tools, for example DU8+, CP3, DP4, DP4+ and J-DP4. We will cover all aspects of NMR simulation focusing on natural products, from the fundamentals to the new computational toolboxes available, combining advanced quantum chemical calculations with complex upstream data processing and machine learning.
The skeleton of the helianane's family is an unsolved controversial topic. Recent synthetic studies and
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C NMR structural analysis have demanded for an amendment of helianane to the open ring ...curcudiol. However, some authors argue that the original helianane structure, a benzofused eight-membered ether ring system, cannot be ruled out immediately without further spectral analyses of curcudiol and helianane. The fact that this compound is extremely rare, obtained only from marine organisms, makes remote the possibility of reisolation. Therefore, we decided to approach this problem computationally. Herein, we performed a complementary quantum mechanical study in order to provide more information about the helianane's actual skeleton. Our
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C NMR chemical shifts calculations suggests that the curcudiol structure is more likely to be the correct one. In addition, we simulated the formation pathways for both products starting from the known biosynthetic precursor. The results show that curcudiol is around 8.0 kcal mol
−1
more stable than the originally proposed helianane structure.
Comprehensive work suggesting the amendment of helianane to the open ring curcudiol by means of computational spectroscopy and thermodynamic reasons.
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Prostate cancer is an important cause of death in the male population and for which there is no satisfactory chemotherapy. Herein a new series of chalcone hybrids containing ...2H-1,2,3-triazole core as the ring B has been synthesized and evaluated in vitro against PC-3 prostate cancer cell line. Compounds 4a, 4c and 4e significantly reduced cell viability and showed IC50 of 28.55, 15.64 and 25.56 µM, respectively. The structure-activity relationship supported by computational chemistry points that the polarity of the molecular surface area should have some relevance to the efficiency of the compounds, in particular the ratio of the partial positive charge sites and the total molecular surface area exposed to the cell environment.
