RESUMO
Transition metal-catalysed carbene- and nitrene transfer to the C1-building blocks carbon monoxide and isocyanides provides heteroallenes (i.e. ketenes, isocyanates, ketenimines and carbodiimides). These are versatile and reactive compounds allowing in situ transformation towards numerous functional groups and organic compounds, including heterocycles. Both one-pot and tandem processes have been developed providing valuable synthetic methods for the organic chemistry toolbox. This review discusses all known transition metal-catalysed carbene- and nitrene transfer reactions towards carbon monoxide and isocyanides and in situ transformation of the heteroallenes hereby obtained, with a special focus on the general mechanistic considerations.
Assuntos
Cianetos , Elementos de Transição , Monóxido de Carbono/química , Iminas , Metano/análogos & derivados , Metano/químicaRESUMO
The first o-iodoxybenzoic acid (IBX) mediated oxidation of unactivated amines to imines is described. A range of meso-pyrrolidines were shown to be suitable substrates. The chemical space was further explored with one-pot oxidative Ugi-type and aza-Friedel-Crafts reactions, which proved to be highly diastereoselective.
Assuntos
Aminas/química , Compostos Aza/química , Iminas/síntese química , Iodobenzenos/química , Iminas/química , Estrutura Molecular , Oxirredução , EstereoisomerismoRESUMO
The detailed molecular mechanism proposed for the MAO-catalyzed oxidation of amines has been controversial with the basic assumption that both MAO A and MAO B follow the same pathway for the C-H bond cleavage step. Using the mechanistic approach of investigation of electronic effects of various benzylamine ring substituents in experiments at pH 9.0, human MAO A exhibits a kinetic behavior characteristic of an H(+) abstraction, while human MAO B exhibits kinetic properties characteristic of a H(-) abstraction. These results lead to the conclusion that the assumption that MAO A and MAO B follow identical mechanisms is incorrect.
Assuntos
Monoaminoxidase/química , Monoaminoxidase/metabolismo , Animais , Benzilaminas/metabolismo , Catálise , Humanos , Hidrogenação , Cinética , Fatores de TempoRESUMO
In this study we evaluated the activity of ABR preparation, a first-in-class agent obtained through fermentation process by genetically unmodified Bacillus spp., in breaking down polysaccharide produced by Streptococcus mutans, primary coloniser of tooth surface and abundant in dental biofilms. Our results showed that ABR preparation is able in degrading sugars formed by S. mutans, both in broth culture and onto teeth surface. Its activity is not influenced by the presence of saliva, commercial mouthwashes or oral disinfectants. ABR preparation has the potential to remove preformed plaque and counteract its development, thus offering conservative control of gingival and periodontal disease.
Assuntos
Biofilmes , Polissacarídeos Bacterianos/metabolismo , Streptococcus mutans/metabolismo , Anti-Infecciosos/farmacologia , Biotecnologia , Fermentação , Antissépticos Bucais/farmacologia , Doenças Periodontais/tratamento farmacológicoRESUMO
Epoxide hydrolases from bacterial and fungal sources are highly versatile biocatalysts for the asymmetric hydrolysis of epoxides on a preparative scale. Besides kinetic resolution, which yields the corresponding enantiomerically enriched vicinal diol and the remaining nonconverted epoxide, enantioconvergent processes are also possible, which lead to the formation of a single enantiomeric diol from a racemic oxirane. The data available to date indicate that the enantioselectivities of enzymes from certain microbial sources can be correlated to the substitutional pattern of various types of substrates: red yeasts (e.g. Rhodotorula or Rhodosporidium sp.) give best enantioselectivities with monosubstituted oxiranes; fungal cells (e.g. from Aspergillus and Beauveria sp.) are best suited for styrene oxide-type substrates; bacterial enzymes, on the other hand (in particular from Actinomycetes such as Rhodococcus and Nocardia sp.) are the biocatalysts of choice for more highly substituted 2,2- and 2,3-disubstituted epoxides.
Assuntos
Bactérias/enzimologia , Epóxido Hidrolases/metabolismo , Leveduras/enzimologia , Compostos de Epóxi/síntese química , Compostos de Epóxi/química , EstereoisomerismoRESUMO
Cell-free transcription-translation systems offer an effective and versatile platform to explore the impact of genetic variations on protein function. We have developed a protocol for preparing linear, mutagenic DNA templates for direct use in the PURE system, enabling the fast and semi-quantitative evaluation of amino acid variations on catalytic activity and stereo-selectivity in native and engineered variants of Old Yellow Enzyme.
Assuntos
NADPH Desidrogenase/metabolismo , Benzaldeídos/química , Benzaldeídos/metabolismo , Sítios de Ligação , Domínio Catalítico , Escherichia coli/metabolismo , Mononucleotídeo de Flavina/química , Mononucleotídeo de Flavina/metabolismo , Biblioteca Gênica , Vetores Genéticos/metabolismo , Simulação de Acoplamento Molecular , Mutagênese , NADPH Desidrogenase/química , NADPH Desidrogenase/genética , Saccharomyces/enzimologiaAssuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Induzidas por Medicamentos/prevenção & controle , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Período Pós-Parto , GravidezAssuntos
Síndrome de Dandy-Walker/diagnóstico , Doenças Fetais/diagnóstico , Hidrocefalia/diagnóstico , Diagnóstico Pré-Natal , Adulto , Líquido Amniótico/análise , Encéfalo/diagnóstico por imagem , Síndrome de Dandy-Walker/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Tomografia Computadorizada por Raios X , Ultrassonografia , Zinco/análiseRESUMO
Tumor microenvironment in carcinomas recruits mesenchymal cells with an abnormal proangiogenic and invasive phenotype. It is not clear whether mesenchymal tumor cells (MTCs) derive from the activation of mature fibroblasts or from their stem cell precursors. However, stromal cell activation in tumors resembles in several aspects the mesenchymal rearrangement which normally occurs during reparative processes such as wound healing. Mesenchymal stem cells (MSCs) play a crucial role in developmental and reparative processes and have extraordinary proangiogenic potential, on the basis of which they are thought to show great promise for the treatment of ischemic disorders. Here, we show that MTCs have proangiogenic potential and that they share the transcriptional expression of the best-known proangiogenic factors with MSCs. We also found that MTCs and MSCs have the same molecular signature for stemness-related genes, and that when co-implanted with cancer cells in syngeneic animals MSCs determine early tumor appearance, probably by favoring the angiogenic switch. Our data (1) reveal crucial aspects of the proangiogenic phenotype of MTCs, (2) strongly suggest their stem origin and (3) signal the risk of therapeutic use of MSCs in tumor-promoting conditions.
Assuntos
Proteínas Angiogênicas/biossíntese , Regulação Neoplásica da Expressão Gênica , Neoplasias Mamárias Animais/metabolismo , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/metabolismo , Neovascularização Patológica/metabolismo , Animais , Linhagem Celular Tumoral , Fibroblastos/metabolismo , Fibroblastos/patologia , Isquemia/metabolismo , Isquemia/patologia , Isquemia/terapia , Neoplasias Mamárias Animais/patologia , Células-Tronco Mesenquimais/patologia , Camundongos , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica/patologia , Ratos , Células Estromais/metabolismo , Células Estromais/patologia , Transcrição Gênica , Transplante IsogênicoRESUMO
Optimization of Radziszewski's four-component reaction employing a microwave-assisted protocol, led to a small library of 48 imidazoles with a success rate of 65% (conversion > 45%). All three diversity points of the four-component reaction were varied. Aromatic and aliphatic inputs were successfully implemented and mono-, di-, tri- and tetrasubstituted imidazoles with various substitution patterns were synthesized. Furthermore, unsymmetrical diketones could successfully be used which improved the intrinsic diversity of the method significantly. If the unsymmetrical diketone 1,2-phenylpropanedione (R1 and R2) was used two regioisomers were formed. Depending on the type of amine (R4) and aldehyde (R3) applied, regioselectivity was modest to good. Based on these results, a reaction mechanism is proposed.
Assuntos
Aldeídos/síntese química , Técnicas de Química Combinatória , Imidazóis/síntese química , Cetonas/química , Micro-Ondas , Aldeídos/efeitos da radiação , Cetonas/síntese química , Cetonas/efeitos da radiação , Estrutura MolecularRESUMO
Chiral epoxides and 1,2-diols, which are central building blocks for the asymmetric synthesis of bioactive compounds, can be obtained by using enzymes--i.e. epoxide hydrolases--which catalyse the enantioselective hydrolysis of epoxides. These biocatalysis have recently been found to be more widely distributed in fungi and bacteria than previously expected. Sufficient sources from bacteria, such as Rhodococcus and Nocardia spp., or fungi, as for instance Aspergillus and Beauveria spp., have now been identified. The reaction proceeds via an SN2-specific opening of the epoxide, leading to the formation of the corresponding trans-configured 1,2-diol. For the resolution of racemic monosubstituted and 2,2- or 2,3-disubstituted substrates, various fungi and bacteria have been shown to possess excellent enantioselectivities. Additionally, different methods, which lead to the formation of the optically pure product diol in a chemical yield far beyond the 50% mark (which is intrinsic to classic kinetic resolutions), are discussed. In addition, the use of non-natural nucleophiles such as azides or amines provides access to enantiomerically enriched vicinal azido- and amino-alcohols. The synthetic potential of these enzymes for asymmetric synthesis is illustrated with recent examples, describing the preparation of some biologically active molecules.