RESUMO

4-Quinolones compose a remarkable class of compounds that show various pharmacological applications. In particular, the activities of both (S) and (R) enantiomers of 2-aryl-2,3-dihydro-4(1H)-quinolones have made them an object of befitting interest for asymmetric synthesis. Although readily yielded as a racemic mixture from an one-pot reaction between 2-aminoacetophenone and benzaldehyde, a pathway for the metal-free enantioselective one-pot synthesis of the (S) isomer is not completely clear. In the present work, guided by the burgeoning role of organocatalysis in asymmetric synthesis and recent experimental insight into the most likely reaction mechanism, we report the in silico screening for a roster of MacMillan chiral imidazolidinones through quantum mechanics calculations. Two stereopredictive models yielding similarly high expected ee (up to 97%) were proposed. The role of aromatic interactions for the control of enantioselectivity was systemically studied, as well as the Pro-S si-enantiofacial attack activation energies, which were found to correlate well (R2 = 0.75) with the reported Bürgi-Dunitz angle for the expected intramolecular Mannich reaction mechanism.

Assuntos

RESUMO

In the 1950s, Alan Turing showed that concerted reactions and diffusion of activating and inhibiting chemical species can autonomously generate patterns without previous positional information, thus providing a chemical basis for morphogenesis in Nature. However, access to these patterns from only one molecular component that contained all the necessary information to execute agonistic and antagonistic signaling is so far an elusive goal, since two or more participants with different diffusivities are a must. Here, we report on a single-molecule system that generates Turing patterns arrested in the solid state, where supramolecular interactions are used instead of chemical reactions, whereas diffusional differences arise from heterogeneously populated self-assembled products. We employ a family of hydroxylated organic salphen building blocks based on a bis-Schiff-base scaffold with portions responsible for either activation or inhibition of assemblies at different hierarchies through purely supramolecular reactions, only depending upon the solvent dielectric constant and evaporation as fuel.

RESUMO

The importance of gem-difunctionalized ketones is represented by their broad applications across chemical boundaries over recent years. The interesting reactivities that this class of compounds possess have made them ideal building blocks to access high-value organic molecules. Furthermore, the gem-difunctionalized ketone moiety has featured in numerous bioactive molecules. For these reasons, a plethora of routes to access such significant molecules have been developed by research groups worldwide - this account looks at delineating the synthesis of gem-difunctionalized ketones from carbonyl substrates, diazo compounds, sulfur ylides and alkynyl reactants.

RESUMO

The study aimed to include the isolated vitexin of Jatropha mutabilis in the ß-cyclodextrin cavity to improve the solubility of this flavone. Its characterization was performed by techniques such as 1H NMR/ROESY (Nuclear Magnetic Resonance Spectroscopy), FT-IR (Infrared Spectroscopy with Fourier Transform), SEM (Morphological analysis of IC by Scanning Electron Microscopy) and dissolution study in vitro. In addition, the following activities were evaluated in the animal models: expectorant, phenol red dosage in bronchoalveolar lavage and antitussive, cough induced by citric acid. In the characterization of the complex, interaction between hydrogens of ring B of vitexin and (H3) of ß-CD was observed, in addition to changes in morphology. In the dissolution test, an increase in the rate of dissolution of vitexin was observed in the first 30 min for the CI vitexin/ß-CD when compared with vitexin. Regarding the pharmacological activity, it was observed that the inclusion complex (IC) vitexin/ß-CD in the equivalent doses of 0.2, 1 and 5 mg/kg of flavone presented higher expectorant activity when compared to vitexin (p < 0.05), suggesting increased bioavailability. As for the antitussive activity, both vitexin and the complex had similar effects and were dose independent. In the toxicity test using Artemia salina, vitexin and IC vitexin/ß-CD were considered non-toxic. At last, the study efficacy of vitexin/ß-CD IC as an expectorant and of vitexin as antitussive. All of these data are being described for the first time.

RESUMO

The aromatic nucleophilic substitution reactions of the nitro group of 4-Nitro-N-alkyl-1,8-naphthalimides by thiolate anions produce fluorescent derivatives and their rates are strongly accelerated by micelles of hexadecyltrimethylammonium chloride even at low pH. Acceleration factors of this reactions can reach million-fold. As the products are oxidant-insensible, this reaction allows the determination of SH- containing compounds such as cysteine, glutathione or proteins even in oxidative conditions. Limits of detection are as low as 5 × 10-7 M, ten times lower than the limit for the classic 5,5'-dithiobis-(2-nitrobenzoic) acid method. Moreover, this reaction can be developed at pHs between 6.5 and 7.5 thereby diminishing the rate of spontaneous oxidation of the thiols. In addition, we demonstrated that 4-Nitro-N-alkyl-1,8-naphthalimides can be used to evidence SH groups in peptides, proteins and living cells.

RESUMO

The presence of internal rotation in sigma bonds is essential for conformational analysis of organic molecules and its understanding is of great relevance in chemistry, as well as in several other areas. However, for aromatic compounds that have substituent groups, withdrawers or donors of electron, there are no data in the literature to explain their rotational barriers. In this context, the work studied the internal rotational barriers of electron donating and withdrawing groups in aromatic compounds using the MP3, MP4, and CCSD(T) methods and the influence of substituents' nature on barrier heights was investigated through calculations based on the theory of Natural Bond Orbitals (NBO) and Quantum Theory of Atoms in Molecules (QTAIM). The results obtained showed that the CCSD(T) method is the one that best describes the internal rotational barriers, followed by MP4 and MP3 and the electron donating groups decrease the barrier, whereas electron withdrawing groups increase. Through the NBO analysis it was possible to observe that for withdrawing groups the interaction of the molecular orbitals is more accentuated promoting the increase of the rotational barrier of these compounds. Through the QTAIM analysis it was possible to show that, for electron donating groups, the internal rotation is influenced by the loss of electronic density when the substituents is perpendicular to the ring plane, however, for withdrawing groups the density is little influenced, regardless of the two conformations (minimum and maximum energy). Two molecules showed free rotation, trichloromethylbenzene and methylbenzene, and the theoretical calculations NBO and QTAIM showed that for these species there is no difference in the properties studied when there is rotation of the dihedral angle.

RESUMO

Gold honey variety pineapple wastes and sacha inchi sub-products (SIS) were characterized in their elemental, physical, and chemical form in order to formulate a supplemented fermentation substrate (SFS) for the growth Weissella cibaria. The peels and fresh cores of the pineapple (FPP, FPC) were dried and ground (PPP, PPC) and then mixed (MCPP). The following procedures were then undertaken: a physicochemical characterization (moisture, aw, pH, acidity, and soluble solids) of the SIS, FPP, FPC, PPP, and PPC; a proximal characterization of he FPP, FPC, SIS, and SFS; and an elemental analysis (C-N2-H2-O2-S) of the MCPP, SIS, and W. cibaria, which allowed the stoichiometric equation to be defined and the SFS to be formulated. We then evaluated the effect that homogenization and heating to boiling point had on the concentration of reducing sugars in the SFS (g L-1). Finally, W. cibaria´s kinetic fermentation parameters were evaluated in the SFS and in a commercial substrate (control). The results showed FPP and FPC yields of 26.02 ± 0.58 and 14.69 ± 1.13%, respectively; a higher total sugar content in FPC (7.21%) than in FPP (6.65%); a high crude protein content in SIS (56.70%), and a C:N2 ratio of 6.50:1.00. Moreover, the highest concentration of reducing sugars (4.44 ± 0.29 g L-1) in the SFS was obtained with 5 h of hydrolysis under homogenization pre-treatments and heating until boiling. The SFS allowed the adaptation of W. cibaria, and there was a biomass production of 2.93 g L-1 and a viability of 9.88 log CFU mL-1. The formulation of an unconventional fermentation substrate from -Agro-industrial wastes of pineapple and sacha inchi to produce valuable products (such as lactic acid biomass through fermentation), is an excellent perspective for large-scale application.

RESUMO

Turpentine is a mixture of monoterpene hydrocarbons obtained as a by-product in the paper industry. In this contribution we present its transformation process towards an alcohol named nopol, that is an important household product and fragrance raw material. Reaction conditions were established for the oxyfuntionalization of crude turpentine oil over Sn-MCM-41 catalyst for the selective conversion of ß-pinene to nopol. Synthesized materials were characterized by XRD, N2 adsorption, FT-IR, TEM and chemical absorption. The reaction was tested in 2 mL glass reactor with a sample of commercial turpentine with α-pinene (55.5% w/w) and ß-pinene (39.5% w/w) as main components and scaled up into a 100 mL Parr reactor, getting 92% conversion of ß-pinene and a nopol selectivity of 93%. The reusability tests showed that the catalyst can be reused 4 times without loss of activity. The results showed that 86% less solvent and 37.5% less paraformaldehyde can be used with turpentine, compared to the conditions used with ß-pinene for getting similar catalysts activity.

RESUMO

In this study, we report our contribution to the application of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of ß-keto-1,2,3-triazole derivatives 3a-f from ethinylestradiol and their application in the inhibition of two human cancer cells lines: human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma (HepG2). The ß-keto-1,2,3-triazole derivates 3a-f exhibited moderate cytotoxic activity for the HepG2 cells with IC50 values of 29.7 µM (3a), 16.4 µM (3b), 17.8 µM (3c), 20.4 µM (3d), 28.1 µM (3e) and 28.2 µM (3f). The semi-synthetic ß-keto-1,2,3-triazoles derivatives 3a-f were all characterized by FT-IR, NMR, HRMS and [α]D.

RESUMO

New N-propargyl tetrahydroquinolines 6a-g have been synthesized efficiently through the cationic Povarov reaction (a domino Mannich/Friedel-Crafts reaction), catalyzed by Indium (III) chloride (InCl3), from the corresponding N-propargylanilines preformed, formaldehyde and N-vinylformamide, with good to moderate yields. All tetrahydroquinoline derivatives obtained were evaluated in vitro as free radical scavengers. Results showed that compound 6c presents a potent antioxidant effect compared with ascorbic acid, used as a reference compound. ADME predictions also revealed favorable pharmacokinetic parameters for the synthesized compounds, which warrant their suitability as potentials antioxidant. Additionally, a theoretical study using Molecular Quantum Similarity and reactivity indices were developed to discriminate different reactive sites in the new molecules in which the oxidative process occurs.