Stereoselective synthesis of S-norvaline and related amino acids through a common intermediate.

A divergent, enantioselective synthetic strategy is reported to produce the non-proteinogenic, biologically active natural amino acids norvaline, 5-hydroxy-4-oxo-L-norvaline, and ɣ-oxonorvaline. These were synthesized in good yields (45-75%) from the common starting material (S)-allylglycine obtained by asymmetric transfer allylation of glycine Schiff base using the Corey catalyst derived from cinchonidine in more than 97% enantiomeric excess.

Differences in Exudates Between Strains of Chlorella sorokiniana Affect the Interaction with the Microalga Growth-Promoting Bacteria Azospirillum brasilense : Differences in Exudates Between Strains of Chlorella sorokiniana Affect the Interaction with the Microalga Growth-Promoting Bacteria Azospirillum brasilense.

The microalga Chlorella sorokiniana and the microalgae growth-promoting bacteria (MGPB) Azospirillum brasilense have a mutualistic interaction that can begin within the first hours of co-incubation; however, the metabolites participating in this initial interaction are not yet identified. Nuclear magnetic resonance (NMR) was used in the present study to characterize the metabolites exuded by two strains of C. sorokiniana (UTEX 2714 and UTEX 2805) and A. brasilense Cd when grown together in an oligotrophic medium. Lactate and myo-inositol were identified as carbon metabolites exuded by the two strains of C. sorokiniana; however, only the UTEX 2714 strain exuded glycerol as the main carbon compound. In turn, A. brasilense exuded uracil when grown on the exudates of either microalga, and both microalga strains were able to utilize uracil as a nitrogen source. Interestingly, although the total carbohydrate content was higher in exudates from C. sorokiniana UTEX 2805 than from C. sorokiniana UTEX 2714, the growth of A. brasilense was greater in the exudates from the UTEX 2714 strain. These results highlight the fact that in the exuded carbon compounds differ between strains of the same species of microalgae and suggest that the type, rather than the quantity, of carbon source is more important for sustaining the growth of the partner bacteria.

Synthesis, characterization and evaluation of prenylated chalcones ethers as promising antileishmanial compounds.

Drug therapy for leishmaniasis remains a major challenge as currently available drugs have limited efficacy, induce serious side-effects and are not accessible to everyone. Thus, the discovery of affordable drugs is urgently needed. Chalcones present a great potential as bioactive agents due to simple structure and functionalization capacity. The antileishmanial activity of different natural and synthetic chalcones have been reported. Here we report the synthesis of twenty-five novel prenylated chalcones that displayed antiparasitic activity in Leishmania mexicana. All the chalcones were evaluated at 5 µg/mL and eleven compounds exhibited a metabolic inhibition close to or exceeding 50%. Compounds 49, 30 and 55 were the three most active with IC50 values < 10 µM. These chalcones also showed the highest selectivity index (SI) values. Interestingly 49 and 55 possessing a substituent at a meta position in the B ring suggests that the substitution pattern influences antileishmanial activity. Additionally, a tridimensional model of fumarate reductase of L. mexicana was obtained by homology modeling. Docking studies suggest that prenylated chalcones could modulate fumarate reductase activity by binding with good affinity to two binding sites that are critical for the target. In conclusion, the novel prenylated chalcones could be considered as promising antileishmanial agents.

Highly selective Diels-Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole.

A highly regio-, chemo- and stereoselective divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels-Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels-Alder cycloaddition with maleimides to furnish octahydropyrrolo[3,4-e]indoles, which served as precursors in the regioselective synthesis of aza-polycyclic skeletons via an intramolecular Heck arylation reaction. Through the latter reaction, the 3-(N-benzyl-2-pyrrolyl)acrylates give rise to 3-(pyrrolo[2,1-a]isoindol-3-yl)acrylates. A further oxidative aromatization of the polycyclic intermediates provides the corresponding polycyclic pyrrolo-isoindoles and isoindolo-pyrrolo-indoles. A theoretical study on the stereoselective Diels-Alder reactions, carried out by calculating the endo/exo transition states, revealed the assistance of non-covalent interactions in governing the endo stereocontrol.

Novel prenyloxy chalcones as potential leishmanicidal and trypanocidal agents: Design, synthesis and evaluation.

The available drugs for treating Leishmaniasis and American trypanosomiasis have high toxicity and multiple side effects, among other problems. More effective and less toxic treatments are urgently needed. A series of chalcones that contained a prenyloxy or geranyloxy substituent was synthesized and characterized. Each substituent was attached to the A ring in some compounds and to the B ring in others, with additional substituents placed on the chalcone moiety. The present aim was to evaluate the effect of the substitution pattern on leishmanicidal and trypanocidal activity. When tested at a single concentration, the compounds exerting a metabolic inhibition close to or exceeding 50% for Leishmania mexicana were 11, 17 and 12, and for Trypanosoma cruzi were 11, 17, 15 and 26. Upon determining the selectivity index (SI =IC50/CC50), the values were 80.9, 1.24 and 55.12 for 11, 17 and 12 (respectively) versus L. mexicana, and 75.1, 1.43, 27.36 and 33.52 for 11, 17, 15 and 26 (respectively) versus T. cruzi. Structural isomers 11 and 17 showed activity for both the L. mexicana and T. cruzi strains, though the greater cytotoxic activity of 17 led to a lower SI. Compounds 12, 15 and 26 were species specific. For T. cruzi, the SI was higher for 11, 15 and 26 than for the reference drugs nifurtimox and benznidazole. The examination of promastigote morphology after exposing L. mexicana and T. cruzi to 11 revealed a decrease in cell density. The current findings suggest that 11 could be a useful lead compound for further SAR studies.

Synthesis of exo-Imidazolidin-2-one Dienes, Their Isomerization, and Selectivity in Diels-Alder Cycloadditions.

An efficient and alternative synthesis of exo-imidazolidin-2-one dienes is described. A condensation reaction was carried out with bis-imino derivatives, diacetyl, and triphosgene, affording symmetrically N, N-disubstituted dienes. The use of alkyl methyl α-diketones led to the formation of nonsymmetrical dienes, which underwent isomerization to provide more stable inner-outer-ring dienes under Lewis acid conditions. Evaluation was made of the reactivity as well as regio- and stereoselectivity of these dienes in Diels-Alder reactions. They proved to be highly reactive and selective. DFT calculations of the transition states accounted for their behavior.

Lipase catalyzed epoxidation of fatty acid methyl esters derived from unsaturated vegetable oils in absence of carboxylic acid.

Nowadays the industrial chemistry reactions rely on green technologies. Enzymes as lipases are increasing its use in diverse chemical processes. Epoxidized fatty acid methyl esters obtained from transesterification of vegetable oils have recently found applications as polymer plasticizer, agrochemical, cosmetics, pharmaceuticals and food additives. In this research article, grapeseed, avocado and olive oils naturally containing high percents of mono and poly unsaturations were used as starting materials for the production of unsaturated fatty acid methyl esters. The effect of lauric acid as an active oxygen carrier was studied on epoxidation reactions where unsaturated fatty acid methyl esters were converted to epoxy fatty acid methyl esters using immobilized Candida antarctica Lipase type B as catalyst and hydrogen peroxide as oxygen donor at mild temperature and pressure conditions. After this study it was confirmed by 1H NMR, 13C NMR and GC-MS that the addition of lauric acid to the enzymatic reaction is unnecessary to transform the alkenes in to epoxides. It was found that quantitative conversions were possible in despite of a carboxylic acid absence.

Effect of Laccase-Mediated Biopolymer Grafting on Kraft Pulp Fibers for Enhancing Paper's Mechanical Properties.

High-resistance paper was manufactured by laccase-grafting of carboxymethyl cellulose (CMC) and chitosan (CPX) on Kraft pulp fiber. The reaction was mediated in the presence of laccase by one of the following polyphenols in the presence of air: gallic acid (GA), vanillic acid (VA) and catechol (1,2⁻DHB). Enzyme was added at constant loading (24 kg ton-1), 1% pulp consistency, 0.005% CMC, pH = 6.3 ± 0.5 and 2 mM of mediator. CPX content was assessed at two levels (0% and 0.005%). Treated pulps were analyzed by different mechanical tests (ring crush, mullen, corrugating medium test (CMT) flat crush of corrugating medium test and tension). An improvement in these parameters was obtained by biopolymer coupling and selected mediator. When using GA, three parameters increased more than 40%, while ring crush increased 120%. For the case of VA, properties were enhanced from 74% to 88% when CPX was added. For 1,2⁻DHB, there was not found a statistically significant difference between the results in the presence of CPX. Scanning electron microscopy, confocal microscopy, FTIR and 13C NMR were used in all papers in order to evaluate grafting. Hence, it was possible to correlate polymerization with an improvement of paper's mechanical properties.

Chemoenzymatic Kinetic resolution of (R)-malathion in aqueous media.

BACKGROUND: Malathion (R,S)-diethyl-2-[(dimethoxyphosphorothioyl)sulfanyl]butanedioate is a chiral organophosphorus compound used widely as pesticide for suppression of harmful insects such as mosquitoes. It is well known that in biological systems (R)-malathion is the active enantiomer, therefore a sustainable approach could be the use of only the biologically active enantiomer. The resolution of the commercial racemic mixture to obtain the pure active enantiomer combined with a recycling of the undesired enantiomer through a racemization process could be an attractive alternative to reduce the environmental impact of this pesticide. Thus, this work evaluates the use of four commercially available lipases for enantioselective hydrolysis and separation of malathion enantiomers from the commercial racemic mixture. RESULTS: Several lipases were methodologically assessed, considering parameters such as enzyme concentration, temperature and reaction rates. Among them, Candida rugosa lipase exhibited the best performance, in terms of enantioselectivity, E = 185 (selective to the (S)-enantiomer). In this way, the desired unreacted (R)-enantiomer was recovered in a 49.42 % yield with an enantiomeric excess of 87 %. The monohydrolized (S)-enantiomer was recovered and racemized in basic media, followed by esterification to obtain the racemic malathion, which was recycled. In this way, an enantioenriched mixture of (R)-malathion was obtained with a conversion of 65.80 % considering the recycled (S)-enantiomer. CONCLUSION: This work demonstrated the feasibility of exploiting Candida rugosa lipase to kinetically resolve racemic malathion through an environmentally friendly recycling of the undesired (S)-enantiomer. Graphical AbstractLipase catalyzed enantioselective resolution of (R)-malathion in aqueous solvent.

Synthesis of a Functionalized Benzofuran as a Synthon for Salvianolic Acid C Analogues as Potential LDL Antioxidants.

A palladium mediated synthesis of a common synthon for the syntheses of antioxidant analogues of naturally occurring salvianolic acids is presented. The synthetic route may be used to obtain analogues with a balanced lipophilicity/hydrophilicity which may result in potentially interesting LDL antioxidants for the prevention of cardiovascular diseases.

Effect of different calcium sources on the bioactive compounds stability of extruded and nixtamalized blue maize flours.

The stability of antioxidants in extruded and nixtamalized blue maize flours with calcium hydroxide [Ca(OH)2] and calcium lactate [C6H10O6Ca] were evaluated. Extruded blue maize flours batches were obtained by mixing blue maize flours separately with different Ca(OH)2 (0.1, 0.2 and 0.3 %) and C6H10O6Ca (0.3, 0.6 and 0.9 %) concentrations respectively and extruded to obtain the extruded flours. For nixtamalized flours, the maize grains were cooked at 1 % Ca(OH)2 and 2.95 % C6H10O6Ca concentrations respectively. Color, antioxidant activity, total phenolics, total anthocyanins and individual anthocyanins, contents were analyzed. Color, antioxidant activity, anthocyanins contents and total phenolics decreased as the calcium hydroxide concentration increased. In contrast, increasing the calcium lactate concentration on the extruded flours had the opposite effect. The extrusion process retained 57-47 %, 72-62 % and 79-65 % of the anthocyanins content, total phenolic content and antioxidant activity, respectively. These retention rates were higher than those of the nixtamalized flours using the same calcium sources. Cyanidin-3-glucoside and pelargonidin-3-glucoside were identified in the maize kernel and flours. Cyanidin-3-glucoside concentration was increased by both extrusion and nixtamalization processed with either of the two calcium sources. In contrast, pelargonidin-3-glucoside concentration decreased by both processes. Other anthocyanins were observed, but they were not identified.

Experimental and quantum chemical studies of a novel synthetic prenylated chalcone.

BACKGROUND: Chalcones are ubiquitous natural compounds with a wide variety of reported biological activities, including antitumoral, antiviral and antimicrobial effects. Furthermore, chalcones are being studied for its potential use in organic electroluminescent devices; therefore the description of their spectroscopic properties is important to elucidate the structure of these molecules. One of the main techniques available for structure elucidation is the use of Nuclear Magnetic Resonance Spectroscopy (NMR). Accordingly, the prediction of the NMR spectra in this kind of molecules is necessary to gather information about the influence of substituents on their spectra. RESULTS: A novel substituted chalcone has been synthetized. In order to identify the functional groups present in the new synthesized compound and confirm its chemical structure, experimental and theoretical 1H-NMR and 13C-NMR spectra were analyzed. The theoretical molecular structure and NMR spectra were calculated at both the Hartree-Fock and Density Functional (meta: TPSS; hybrid: B3LYP and PBE1PBE; hybrid meta GGA: M05-2X and M06-2X) levels of theory in combination with a 6-311++G(d,p) basis set. The structural parameters showed that the best method for geometry optimization was DFT:M06-2X/6-311++G(d,p), whereas the calculated bond angles and bond distances match experimental values of similar chalcone derivatives. The NMR calculations were carried out using the Gauge-Independent Atomic Orbital (GIAO) formalism in a DFT:M06-2X/6-311++G(d,p) optimized geometry. CONCLUSION: Considering all HF and DFT methods with GIAO calculations, TPSS and PBE1PBE were the most accurate methods used for calculation of 1H-NMR and 13C-NMR chemical shifts, which was almost similar to the B3LYP functional, followed in order by HF, M05-2X and M06-2X methods. All calculations were done using the Gaussian 09 software package. Theoretical calculations can be used to predict and confirm the structure of substituted chalcones with good correlation with the experimental data.

Pyrene-fullerene C60 dyads as light-harvesting antennas.

A series of pyrene-fullerene C60 dyads bearing pyrene units (PyFC12, PyFPy, Py2FC12 and PyFN) were synthesized and characterized. Their optical properties were studied by absorption and fluorescence spectroscopies. Dyads were designed in this way because the pyrene moeities act as light-harvesting molecules and are able to produce "monomer" (PyFC12) or excimer emission (PyFPy, Py2FC12 and PyFN). The fluorescence spectra of the dyads exhibited a significant decrease in the amount of pyrene monomer and excimer emission, without the appearance of a new emission band due to fullerene C60. The pyrene fluorescence quenching was found to be almost quantitative, ranging between 96%-99% depending on the construct, which is an indication that energy transfer occurred from one of the excited pyrene species to the fullerene C60.

Electronic Control of Product Distribution in the [5+5]-Coupling of ortho-Alkynylbenzaldehyde Derivatives and γ,δ-Unsaturated Carbene Complexes.

The coupling of highly oxygenated ortho-alkynylbenzaldehyde derivatives with γ,δ-carbene complexes was evaluated systematically. In all of the electron-rich systems investigated the exclusive product of the reaction is the dihydrophenanthrene derivative. Only the extremely electron withdrawing methanesulfonate group can prevent this process from occurring. The use of the base additive collidine resulted in a surprising yield enhancement but no other discernable effect on the course of the reaction. Dihydrophenanthrene formation was attributed to rapid dehydration after the opening of a benzo-oxanorbornene intermediate.

Synthesis of hydronaphthalenes through coupling of enyne carbonyl compounds that contain pendant alkene groups with Fischer carbene complexes.

The coupling of enyne carbonyl compounds that contain pendant alkene groups with Fischer carbene complexes to afford furans that contain pendant alkene groups is described. Subsequent intramolecular Diels-Alder reactions are effective in select cases, resulting in hydronaphthalene systems after dehydration. Although the Diels-Alder event is thermodynamically unfavorable, the overall transformation of alkene-furans to dihydronaphthalenes is a favorable process.

Total synthesis of antofine using the net [5+5]-cycloaddition of gamma,delta-unsaturated carbene complexes and 2-alkynylphenyl ketones as a key step.

A compound containing all of the carbons of the anticancer agent antofine was produced in a single step from the coupling of a gamma,delta-unsaturated carbene complex with a 2-alkynylphenyl ketone derivative. Subsequent conversion to antofine was effected in three steps.