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1.
Top Curr Chem (Cham) ; 377(5): 23, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463700

RESUMO

Since the pioneering independent reports of Akiyama and Terada, the use of chiral phosphoric acids (CPAs) and derivatives as a versatile tool for asymmetric synthesis with good reactivity, regioselectivity, diastereoselectivity and enantioselectivity has emerged, forming an important part of the implementation of asymmetric counteranion-directed catalysis reported to date. In these achievements, the combination of metals with CPAs has enabled various catalytic modes beyond the scope of typical acid catalysis, such as relay catalysis, ion-pairing catalysis, and binary acid catalysis. The first-row transition metals (Sc-Zn) are considered to be sustainable transition metals and have received a great deal of attention. These naturally abundant metals display excellent Lewis acidity and function as powerful redox catalysts in synthesis involving both one and two-electron transfers. Hence, in this chapter, we summarize recent advances in the development of asymmetric reactions using a combination of first-row transition metals and CPAs. Furthermore, we provide a detailed discussion of the mechanisms involved in order to understand the interaction of the metal/phosphate and the origins of the asymmetric control of the transformations.


Assuntos
Alcenos/síntese química , Compostos Organometálicos/química , Ácidos Fosfóricos/química , Elementos de Transição/química , Alcenos/química , Catálise , Estrutura Molecular
2.
Talanta ; 204: 762-768, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357363

RESUMO

Herein we reported a two-photon (TP) fluorescence "turn-on" probe MNPO, exhibiting high selectivity and sensitivity towards intracellular cysteine (Cys) with excellent lysosomal localization. The probe displayed fast response towards Cys over homocysteine (Hcy), glutathione (GSH), and other various analytes under physiological conditions. Low cytotoxicity made it successful for TP imaging of Cys in HeLa cells with an ultralow probe concentration of 250 nM, and a rapid response of only 10 min. Simultaneously, colocalization experiments in lysosome demonstrated its ability for specific in situ detection of lysosomal Cys in living cells, which shed light on its potential applications in biomedical applications. Beyond that MNPO was successfully applied for TP imaging of Cys in mice organ tissues such as heart, liver, and spleen, and the penetration depth of mice heart tissue was up to 184 µm, which disclosed the predominant TP characteristic. We believe that this study will provide some useful information toward diagnosis and treatment of pathogenesis associated with Cys or lysosomes in future.


Assuntos
Cisteína/análise , Corantes Fluorescentes/química , Lisossomos/metabolismo , Alcenos/síntese química , Alcenos/química , Alcenos/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Naftalenos/síntese química , Naftalenos/química , Naftalenos/toxicidade , Fótons
3.
Org Biomol Chem ; 17(27): 6607-6611, 2019 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-31237304

RESUMO

Synergistic palladium and enamine catalysis was explored to promote ketone addition to unactivated olefins. A secondary amine-based organocatalyst was identified as the optimal co-catalyst for the directed Pd-catalyzed alkene activation. Furthermore, asymmetric hydrocarbon functionalization of unactivated alkenes was also achieved with good to excellent yield (up to 96% yields) and stereoselectivity (up to 96% ee). This strategy presented an efficient approach to prepare α-branched ketone derivatives under mild conditions.


Assuntos
Alcenos/química , Hidrocarbonetos/química , Cetonas/química , Paládio/química , Alcenos/síntese química , Aminas/química , Catálise , Hidrocarbonetos/síntese química , Cetonas/síntese química , Estereoisomerismo
4.
Nat Chem ; 11(5): 478-487, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30936524

RESUMO

Nitriles are found in many bioactive compounds, and are among the most versatile functional groups in organic chemistry. Despite many notable recent advances, however, there are no approaches that may be used for the preparation of di- or tri-substituted alkenyl nitriles. Related approaches that are broad in scope and can deliver the desired products in high stereoisomeric purity are especially scarce. Here, we describe the development of several efficient catalytic cross-metathesis strategies, which provide direct access to a considerable range of Z- or E-di-substituted cyano-substituted alkenes or their corresponding tri-substituted variants. Depending on the reaction type, a molybdenum-based monoaryloxide pyrrolide or chloride (MAC) complex may be the optimal choice. The utility of the approach, enhanced by an easy to apply protocol for utilization of substrates bearing an alcohol or a carboxylic acid moiety, is highlighted in the context of applications to the synthesis of biologically active compounds.


Assuntos
Alcenos/síntese química , Técnicas de Química Sintética/métodos , Nitrilos/síntese química , Catálise , Complexos de Coordenação/química , Molibdênio/química , Estereoisomerismo
5.
Org Lett ; 21(6): 1926-1929, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30821980

RESUMO

Cu(II)-mediated direct NH2 and NH alkyl aryl aminations and olefin aziridinations are described. These room-temperature, one-pot, environmentally friendly procedures replace costly Rh2 catalysts and, in some instances, display important differences with comparable Rh2- and Fe-supported reactions.


Assuntos
Alcenos/química , Aziridinas/química , Cobre/química , Alcenos/síntese química , Aminação , Aziridinas/síntese química , Catálise , Estrutura Molecular
6.
Molecules ; 24(5)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30866406

RESUMO

A series of novel phosphorylated penta-1,4-dien-3-one derivatives were designed and synthesized. The structures of all title compounds were determined by ¹H-NMR, 13C-NMR, 31P-NMR, and high-resolution mass spectrometry (HRMS). Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compound 3g exhibited substantial antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), with a 50% effective concentration (EC50) value of 8.6 µg/mL, which was significantly superior to bismerthiazol (BT) (58.8 µg/mL) and thiodiazole-copper (TC) (78.7 µg/mL). In addition, compound 3h showed remarkable protective activity against tobacco mosaic virus (TMV), with an EC50 value of 104.2 µg/mL, which was superior to that of ningnanmycin (386.2 µg/mL). Furthermore, the microscale thermophoresis and molecular docking experiments on the interaction of compounds 3h and 3j with TMV coat protein (TMV CP) were also investigated. Compounds 3h and 3j bound to TMV CP with dissociation constants of 0.028 and 0.23 µmol/L, which were better than that of ningnanmycin (0.52 µmol/L). These results suggest that novel phosphorylated penta-1,4-dien-3-one derivatives may be considered as an activator for antibacterial and antiviral agents.


Assuntos
Alcenos/síntese química , Antibacterianos/síntese química , Antivirais/síntese química , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Xanthomonas/efeitos dos fármacos , Alcadienos , Alcenos/química , Alcenos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antivirais/química , Antivirais/farmacologia , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Desenho de Drogas , Testes de Sensibilidade Microbiana , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosforilação , Relação Estrutura-Atividade , Vírus do Mosaico do Tabaco/metabolismo
7.
Bioorg Med Chem ; 27(5): 822-831, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30718063

RESUMO

To discover new, potent, and selective inhibitors for the murine gamma-aminobutyric acid transporter 4 (mGAT4), the structure-activity relationship (SAR) study of a new cis-alkene analog family based on DDPM-1457 [(S)-2], which previously showed promising inhibitory potency at and subtype selectivity for mGAT4, was conducted. To uncover the importance of the differences between the trans- and the cis-alkene moiety in the spacer, the present publication describes the synthesis of the new compounds via catalytic hydrogenation with Lindlar's catalyst. The biological results collected by the SAR study revealed that analog rac-7j characterized by a four-instead of a three-carbon atom spacer with a cis double bond applying to the majority of the studied compounds displays a surprisingly high potency at mGAT1 (pIC50 = 6.00 ±â€¯0.04) and at the same time a reasonable potency at mGAT4 (pIC50 = 4.82).


Assuntos
Alcenos/farmacologia , Inibidores da Captação de GABA/farmacologia , Ácidos Nipecóticos/farmacologia , Alcenos/síntese química , Alcenos/química , Animais , Desenho de Drogas , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Inibidores da Captação de GABA/síntese química , Inibidores da Captação de GABA/química , Células HEK293 , Humanos , Camundongos , Ácidos Nipecóticos/síntese química , Ácidos Nipecóticos/química , Estereoisomerismo , Relação Estrutura-Atividade , Tiagabina/farmacologia
8.
J Asian Nat Prod Res ; 21(7): 702-715, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30596267

RESUMO

Desmosdumotin C (Des C), a natural product isolated from the roots of Desmos dumosus, has shown good antitumor activity. A three dimensional quantitative structure-activity relationship (QSAR) study using the comparative molecular field analysis (CoMFA) method was performed on 32 Des C analogues. Based on the QSAR, 18 new Des C analogues were designed and synthesized. An efficient three-step synthetic strategy toward Des C and its analogues was developed from commercial available 2, 4, 6-trihydroxyacetophenone. All synthesized compounds were evaluated against a panel of human cancer cell lines and showed ED50 values ranging from 1.1 to 25.1 µΜ.


Assuntos
Alcenos/síntese química , Alcenos/farmacologia , Annonaceae/química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Cetonas/síntese química , Cetonas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Quantitativa Estrutura-Atividade
9.
J Am Chem Soc ; 140(51): 17878-17883, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30525575

RESUMO

A nickel-catalyzed conjunctive cross-coupling of simple alkenyl amides with aryl iodides and aryl boronic esters is reported. The reaction is enabled by an electron-deficient olefin (EDO) ligand, dimethyl fumarate, and delivers the desired 1,2-diarylated products with excellent regiocontrol. Under optimized conditions, a wide range of amides derived from 3-butenoic acid, 4-pentenoic acid, and allyl amine are compatible substrates. This method represents the first example of regiocontrolled 1,2-diarylation directed by a native amide functional group. Computational analysis sheds light on the potential substrate binding mode and the role of the EDO ligand in the reductive elimination step.


Assuntos
Alcenos/síntese química , Amidas/síntese química , Ácidos Borônicos/química , Complexos de Coordenação/química , Iodobenzenos/química , Níquel/química , Catálise , Fumarato de Dimetilo/química , Ligantes , Modelos Químicos
10.
Org Lett ; 20(22): 7345-7350, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30407833

RESUMO

A photocatalytic method for the oxyamination of alkenes using simple nucleophilic nitrogen atom sources in place of prefunctionalized electrophilic nitrogen atom donors is reported. Copper(II) is an inexpensive, practical, and uniquely effective terminal oxidant for this process. In contrast to oxygen, peroxides, and similar oxidants commonly utilized in non-photochemical oxidative methods, the use of copper(II) as a terminal oxidant in photoredox reactions avoids the formation of reactive heteroatom-centered radical intermediates that can be incompatible with electron-rich functional groups. As a demonstration of the generality of this concept, it has been shown that diamination and deoxygenation reactions can also be accomplished using similar photooxidative conditions.


Assuntos
Alcenos/química , Alcenos/síntese química , Cobre/química , Oxidantes/química , Oxigênio/química , Aminação , Catálise , Hidroxilação , Estrutura Molecular , Oxirredução , Sais
11.
Bioorg Med Chem ; 26(22): 5824-5837, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30429098

RESUMO

Two series of novel pyridoxine-based azaheterocyclic analogs of feruloyl methane (Dehydrozingerone, DZG) were synthesized, and their biological activity against a panel of tumor and normal cell lines was evaluated in vitro. The most active compounds possessed expressed cytotoxic activity, which was comparable to cytotoxic activity of doxorubicin and significantly higher than that of DZG, and a remarkable selectivity for the studied cancer cell lines as compared to the normal cells. The leading compound and DZG initiated arrest of the cell cycle in the G2/M phase, preventing normal division and further transition of daughter cells to the G0/G1 phase. Similar to DZG, but with higher efficiency, the leading compound was able to inhibit migration activity and, therefore, invasiveness of tumor cells. It also increased concentration of reactive oxygen species in tumor cells, induced depolarization of mitochondrial membranes and initiated apoptosis accompanied by disruption of integrity of cytoplasmic cell membranes. By contrast to DZG, the leading compound did not possess antioxidant properties. The obtained data make the described chemotype a promising starting point for the development of new anticancer agents.


Assuntos
Alcenos/farmacologia , Antineoplásicos/farmacologia , Metano/farmacologia , Piridoxina/farmacologia , Alcenos/síntese química , Alcenos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Metano/análogos & derivados , Modelos Moleculares , Estrutura Molecular , Piridoxina/síntese química , Piridoxina/química , Relação Estrutura-Atividade
12.
J Am Chem Soc ; 140(42): 13634-13639, 2018 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-30289691

RESUMO

Substituted 1,3-dienes are valuable synthetic intermediates used in myriad catalytic transformations, yet modern catalytic methods for their preparation in a highly modular fashion using simple precursors are relatively few. We report here an aerobic boron Heck reaction with cyclobutene that forms exclusively linear 1-aryl-1,3-dienes using (hetero)arylboronic acids, or 1,3,5-trienes using alkenylboronic acids, rather than typical Heck products (i.e., substituted cyclobutenes). Experimental and computational mechanistic data support a pericyclic mechanism for C-C bond cleavage that enables the cycloalkene to circumvent established limitations associated with diene reagents in Heck-type reactions.


Assuntos
Alcenos/síntese química , Ácidos Borônicos/química , Alcenos/química , Ácidos Borônicos/síntese química , Técnicas de Química Sintética , Ciclobutanos/síntese química , Ciclobutanos/química , Oxigênio/química , Estereoisomerismo
13.
Angew Chem Int Ed Engl ; 57(51): 16857-16860, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30358060

RESUMO

The development of a general, nickel-catalyzed alkyl-Mizoroki-Heck reaction of unactivated alkyl bromides is described. The mild reaction proceeds efficiently using a wide range of primary and secondary alkyl bromides, and examples of intermolecular cross-couplings are provided. Reaction alkene regioselectivity is significantly enhanced over prior carbocyclizations using palladium catalysis. Mechanistic investigations are consistent with a direct carbocyclization in contrast to the auto-tandem atom-transfer cyclization and halide elimination previously observed with palladium catalysis.


Assuntos
Alcenos/síntese química , Hidrocarbonetos Bromados/química , Níquel/química , Alcenos/química , Catálise , Ciclização , Estrutura Molecular , Estereoisomerismo
14.
J Chem Ecol ; 44(12): 1115-1119, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30306314

RESUMO

We describe the identification, synthesis, and field bioassays of a novel aggregation-sex pheromone produced by males of Susuacanga octoguttata (Germar), a South American cerambycid beetle. Analyses of extracts of headspace volatiles produced by adult beetles revealed a sex-specific compound emitted by males which was identified as (Z)-7-hexadecene by microchemical and spectroscopic analyses. The synthesized pheromone was attractive to beetles of both sexes in field trials. This unsaturated hydrocarbon motif is unprecedented among cerambycid pheromones identified to date. During field bioassays, we serendipitously discovered that adults of S. octoguttata trapped in two Brazilian biomes differed considerably in elytral markings, although males from both populations produced (Z)-7-hexadecene as an aggregation-sex pheromone.


Assuntos
Alcenos/síntese química , Besouros/fisiologia , Atrativos Sexuais/química , Alcenos/química , Alcenos/farmacologia , Animais , Besouros/química , Feminino , Masculino , Atrativos Sexuais/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , América do Sul , Espectrometria de Massas por Ionização por Electrospray , Estereoisomerismo
15.
Org Biomol Chem ; 16(38): 6870-6875, 2018 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-30229798

RESUMO

Photoexcitation of dibenzalacetones (1a-d) in homogeneous media and solid state yields a mixture of products with poor conversions. Irradiation of the reactants complexed to γ-cyclodextrin predominantly affords a single dimer (syn adduct 6) despite the possibility for several monomeric and dimeric products. High selectivity in the cavitand-mediated reaction along with the structural characterization of the inclusion complex provides insight into the supramolecular interactions that drive the self-assembly of the host-guest system.


Assuntos
Alcenos/química , gama-Ciclodextrinas/química , Alcenos/síntese química , Hidrocarbonetos Aromáticos com Pontes/síntese química , Hidrocarbonetos Aromáticos com Pontes/química , Chalconas/síntese química , Chalconas/química , Reação de Cicloadição , Dimerização , Imidazóis/síntese química , Imidazóis/química , Luz , Modelos Moleculares , Estereoisomerismo , gama-Ciclodextrinas/síntese química
16.
Sci Rep ; 8(1): 12784, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30143727

RESUMO

Inflammation plays a major role in the onset and development of chronic non-communicable diseases like obesity, cardiovascular diseases and cancer. Combined, these diseases represent the most common causes of death worldwide, thus development of novel pharmacological approaches is crucial. Electrophilic nitroalkenes derived from fatty acids are formed endogenously and exert anti-inflammatory actions by the modification of proteins involved in inflammation signaling cascades. We have developed novel nitroalkenes derived from α-tocopherol aiming to increase its salutary actions by adding anti-inflammatory properties to a well-known nutraceutical. We synthesized and characterized an α-tocopherol-nitroalkene (NATOH) and two hydrosoluble analogues derived from Trolox (NATxME and NATx0). We analyzed the kinetics of the Michael addition reaction of these compounds with thiols in micellar systems aiming to understand the effect of hydrophobic partition on the reactivity of nitroalkenes. We studied NATxME in vitro showing it exerts non-conventional anti-inflammatory responses by inducing Nrf2-Keap1-dependent gene expression and inhibiting the secretion of NF-κB dependent pro-inflammatory cytokines. NATxME was also effective in vivo, inhibiting neutrophil recruitment in a zebrafish model of inflammation. This work lays the foundation for the rational design of a new therapeutic strategy for the prevention and treatment of metabolic and inflammation-related diseases.


Assuntos
Alcenos/síntese química , Alcenos/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Transdução de Sinais , Tocoferóis/síntese química , Tocoferóis/farmacologia , Alcenos/química , Animais , Anti-Inflamatórios/química , Cromanos/síntese química , Cromanos/química , Cromanos/farmacologia , Cinética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Micelas , Infiltração de Neutrófilos/efeitos dos fármacos , Células RAW 264.7 , Tocoferóis/química , Peixe-Zebra
17.
J Am Chem Soc ; 140(38): 12181-12188, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30160479

RESUMO

The covalent coupling of complex macromolecules is a modern challenge in both chemistry and biology. The development of efficient and chemoselective methods for polymer coupling and functionalization are increasingly important for designing new advanced materials and interfacing with biochemical systems. Herein, we present a new strategy to directly conjugate living polymers prepared using ring-opening metathesis polymerization (ROMP) to both small molecules and synthetic macromolecules. Central to this methodology is a terminal alkyne that serves as a directing group to promote a rapid, intramolecular reaction with an otherwise unreactive olefin. This highly chemoselective relay conjugation is compatible with a range of monomer families and uses a bench-stable enyne motif that can be easily introduced to functional targets. The rapid rate of the conjugation reaction paves the way for greatly streamlined construction of complex macromolecular systems derived from metathesis polymerization techniques without the need for specialized equipment.


Assuntos
Polímeros/síntese química , Alcenos/síntese química , Alcenos/química , Alquinos/síntese química , Alquinos/química , Catálise , Polimerização , Rutênio/química
18.
J Am Chem Soc ; 140(36): 11202-11205, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30156404

RESUMO

The first catalytic strategy to harness imidate radicals has been developed. This approach enables alkene difunctionalization of allyl alcohols by photocatalytic reduction of their oxime imidates. The ensuing imidate radicals undergo consecutive intra- and intermolecular reactions to afford (i) hydroamination, (ii) aminoalkylation, or (iii) aminoarylation, via three distinct radical mechanisms. The broad scope and utility of this catalytic method for imidate radical reactivity is presented, along with comparisons to other N-centered radicals and complementary, closed-shell imidate pathways.


Assuntos
Alcenos/síntese química , Imidoésteres/química , Propanóis/química , Alcenos/química , Catálise , Radicais Livres/química , Estrutura Molecular
19.
Macromol Rapid Commun ; 39(18): e1800414, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30085385

RESUMO

In this study, π-conjugated poly(arylenevinylene)s are synthesized via the Pd-catalyzed dehydrogenative direct alkenylation of polyfluoroarenes with diethenyl aromatic monomer. The introduction of a fluoro group promotes the cross-coupling reaction, and the formation of the undesired homocoupling byproduct is minimized by optimizing the reaction conditions. The polycondensation reactions lead to the formation of poly(arylenevinylene)s with a well-defined trans-configuration. The obtained polymers are evaluated as emitting materials for organic light-emitting diodes.


Assuntos
Alcenos/síntese química , Hidrocarbonetos Fluorados/química , Paládio/química , Polivinil/síntese química , Alcenos/química , Catálise , Hidrogenação , Estrutura Molecular , Polivinil/química
20.
J Am Chem Soc ; 140(32): 10126-10130, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30084247

RESUMO

We report a Rh-catalyst for accessing olefins from primary alcohols by a C-C bond cleavage that results in dehomologation. This functional group interconversion proceeds by an oxidation-dehydroformylation enabled by N, N-dimethylacrylamide as a sacrificial acceptor of hydrogen gas. Alcohols with diverse functionality and structure undergo oxidative dehydroxymethylation to access the corresponding olefins. Our catalyst protocol enables a two-step semisynthesis of (+)-yohimbenone and dehomologation of feedstock olefins.


Assuntos
Álcoois/química , Alcenos/síntese química , Catálise , Metilação , Estrutura Molecular , Oxirredução
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