RESUMO
This communication describes a solution to the vexing problem of synthesis of 4-nitroisoxazolidine rings from cyclic nitrones and ß-nitrostyrenes. The trans-endo adduct 2 is quantitatively synthesised from E-ß-nitrostyrene under mild conditions avoiding purification, while the trans-exo adduct 4 is obtained at higher temperatures. Furthermore, a Crystallization-Induced Diastereomer Transformation (CIDT) process was used to epimerise the NO2 bond from 2 to the cis-exo adduct 3 with total conversion assisted by the para-halogen substitution of the aromatic ring without any additives. By combining these approaches, we can establish a simple synthetic methodology that allows the diastereoselective synthesis of three diastereoisomers, overcoming the previous problems described in the literature.
RESUMO
The synthesis of 5-chloro-8-nitro-1-naphthoyl chloride and its use as a protective group for amines is described. Protection is carried out with an auxiliary amine or under mild Schotten-Baumann conditions in high yield (>86%), while deprotection can be achieved easily under gentle reducing conditions due to the large steric tension between C-1 and C-8 naphthalene substituents. The reaction has been successfully tested in dipeptide synthesis and amino alcohols protection, and it has proved selective for the ε-amine group of lysine.
Assuntos
Aminas , Aminoácidos , Aminas/química , Amino Álcoois/química , Lisina/química , DipeptídeosRESUMO
The ability of a series of electron-deficient aromatic compounds to form charge-transfer complexes with tryptophan in water has been evaluated by X-ray diffraction studies, UV-vis spectra and NMR. As dinitrophenyl (DNP) ligands are well-known to generate antibody-mediated responses and the π-π stacking interactions with tryptophan residues of the antibody Fab fragment have been reported, most of the aromatic receptors studied here are nitro derivatives. Charge-transfer interactions between the rich indole ring of tryptophan and the electron-deficient aromatic receptors have been observed in the solid state, as four crystal structures of the complexes were obtained. The aromatic donor-acceptor interactions in solution were also verified by UV-vis and NMR spectroscopy. The association of the tripeptide Trp-Gly-Trp, a motif found in antigen Ag43, with the electron-deficient aromatic diimide was also studied by UV-vis and NMR spectroscopy. Our results show that these simple electron-deficient molecules could potentially behave as novel haptens and be incorporated in more elaborated drugs targeting protein-protein interactions, due to the synergistic effect of multiple non-covalent interactions.
Assuntos
Elétrons , Triptofano , Triptofano/química , Água/química , Haptenos , Indóis/química , Fragmentos Fab das ImunoglobulinasRESUMO
The synthesis of small molecules able to mimic the active site of hydrolytic enzymes has been largely pursued in recent decades. The high reaction rates and specificity shown by natural hydrolases present an attractive target, and yet the preparation of suitable small-molecule mimics remains challenging, requiring activated substrates to achieve productive outcomes. Here we present small synthetic artificial enzymes which mimic the catalytic site and the oxyanion hole of chymotrypsin and N-terminal hydrolases and are able to perform, for the first time, the transesterification of a non-activated ester such as ethyl acetate with methanol under mild and neutral reaction conditions.
Assuntos
Ésteres , Hidrolases , Domínio Catalítico , Esterificação , Ésteres/química , Hidrolases/metabolismo , HidróliseRESUMO
Cleft type receptors showing the oxyanion hole motif have been prepared in a straightforward synthesis starting from the commercial 3,7-dihidroxy-2-naphthoic acid. The double H-bond donor pattern is achieved by the introduction of a sulfonamide group in the C-8 position of naphthalene and a carboxamide at the C-2 position. This cleft, for which the geometry resembles that of an oxyanion hole, is able to adjust to different guests, as shown by the analysis of the X-ray crystal structures of associates with methanol or acetic acid. Combination of hydrogen bonds and charge-transfer interactions led to further stabilization of the complexes, in which the electron-rich aromatic ring of the receptor was close in space to the electron-deficient dinitroaromatic guests. Modelling studies and bidimensional NMR experiments have been carried out to provide additional information.
Assuntos
Naftalenos , Sulfonamidas , Ligação de HidrogênioRESUMO
Using supramolecular interactions, a novel macrocyclic receptor is able to selectively extract zwitterionic phenylglycine from neutral aqueous solutions into chloroform with up to 91.8% ee. Modeling studies, nuclear magnetic resonance experiments, and X-ray diffraction analysis were carried out to explain the high enantioselectivity observed.
Assuntos
Glicina/análogos & derivados , Compostos Macrocíclicos/química , Clorofórmio/química , Cristalografia por Raios X , Glicina/química , Glicina/isolamento & purificação , Modelos Moleculares , Estrutura Molecular , EstereoisomerismoRESUMO
A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different ß-disubstituted-α,ß-unsaturated aldehydes with a chiral α,ß-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner.
Assuntos
Aldeídos/química , Cicloexenos/síntese química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cristalografia por Raios X , Cicloexenos/química , Modelos Moleculares , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , EstereoisomerismoRESUMO
The title compound, C22H25NO5, was prepared by CAN [cerium(IV) ammonium nitrate] oxidation of the corresponding ß-lactam. The dihedral angle between the benzene rings is 13.3â (4)° and the C-N-C(=O)-C torsion angle is 176.1â (6)°. In the crystal, amide-C(4) N-Hâ¯O and reinforcing C-Hâ¯O hydrogen bonds link the mol-ecules into infinite [010] chains. Further C-Hâ¯O hydrogen bonds cross-link the chains in the c-axis direction.
RESUMO
The title compound, C12H15NO3S, was prepared by 1,3-dipolar cyclo-addition of 3,4-di-hydro-2H-pyrrole 1-oxide and phenyl vinyl sulfone. In the mol-ecule, both fused five-membered rings display a twisted conformation. In the crystal, C-Hâ¯O hydrogen bonds link neighbouring mol-ecules, forming chains running parallel to the b axis.
RESUMO
A molecular receptor has been synthesized joining an aza-crown ether with a chiral chromane which mimics the oxyanion hole of the enzymes. With this receptor an apolar host-guest complex with zwitterionic alanine has been achieved through the formation of up to seven H-bonds. This complex allows the extraction of aqueous alanine to a chloroform phase, while other natural amino acids are poorly extracted or are not extracted at all. Due to the chiral nature of the receptor, enantioselective extraction from the aqueous alanine solution to a chloroform phase takes place. X-Ray analysis combined with anisotropic effects, NOE and CD studies revealed the absolute configuration of both strong and weak complexes. Modelling studies also support the proposed structures. The presence of an oxyanion-hole motif in this structure was corroborated by X-ray diffraction studies.
Assuntos
Alanina/isolamento & purificação , Compostos Aza/química , Cromanos/química , Éteres de Coroa/química , Alanina/química , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares , Conformação Molecular , EstereoisomerismoRESUMO
Administration of enantiomerically pure ß-adrenergic agonists and antagonists increases their activity and reduces side effects. We report here a small-molecule artificial receptor (SMAR) that, by mimicking the ß-adrenergic receptor, is able to enantioselectively extract commercial ß-adrenergic interacting drugs. The selectivity is justified according to DFT calculations and X-ray diffraction experiments.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Receptores Adrenérgicos beta/química , Receptores Artificiais/metabolismo , Humanos , Teoria Quântica , EstereoisomerismoRESUMO
A chiral chromane receptor has been synthesized which mimics the oxyanion hole of the enzymes. In this receptor H-bonds and cation-π interactions team up to generate an apolar host-guest complex with zwitterionic proline. This complex allows the extraction of only proline to a chloroform phase, while no other natural amino acids are extracted. Due to the chiral nature of the receptor, enantioselective extraction from the aqueous proline solution to a chloroform phase takes place. L-Proline provided an easy method to resolve the receptor racemic mixture, while anisotropic effects, NOE and CD studies revealed the absolute configuration of the receptor. Modelling studies also support the proposed structures. The presence of an oxyanion-hole motif in this structure was corroborated by X-ray diffraction studies.
Assuntos
Benzopiranos/química , Compostos de Fenilureia/química , Prolina/química , Clorofórmio/química , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular , Prolina/isolamento & purificaçãoRESUMO
The first organocatalytic synthesis of cis-decalins using sulfonyl Nazarov reagents is reported. The Jørgensen's catalyst directs this highly enantioselective synthesis using different cyclohexenal derivatives.
Assuntos
Técnicas de Química Sintética , Naftalenos/química , Catálise , Estrutura Molecular , Naftalenos/síntese química , Ressonância Magnética Nuclear BiomolecularRESUMO
A new chiral benzofuran receptor has been synthesized and its properties in the association of amino acid derivatives have been studied. X-ray structures were obtained and these corroborate the presence of an oxyanion-hole motif in these structures.
Assuntos
Ânions/química , Benzofuranos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares , EstereoisomerismoRESUMO
BACKGROUND: To evaluate the use of surveillance cultures (SCs) to prevent catheter-related bloodstream infections (CRBSIs) in asymptomatic hemodialysis (HD) patients. METHODS: In 2011-2012, we conducted a prospective study of HD patients with tunneled cuffed central venous catheters (TCCs). Colonization of the catheter lumen was assessed every 15 days by inoculating ~5 mL endoluminal blood into aerobic culture bottles. Individual patients were triaged based on SC results: group 1 (negative); group 2 (coagulase-negative Staphylococcus [CoNS] with time-to-positivity (TTP) >14 hours); group 3 (CoNS with TTP ≤14 hours); and group 4 (any microorganism other than CoNS and any TTP). RESULTS: We studied 104 patients (129 TCCs). Median follow-up was 262.5 days (interquartile range [IR], 135.0-365.0). A total of 1,734 SCs were collected (median, 18 per patient; IR, 10.0-24.0), of which 1,634 (94.2%) were negative (group 1) and 100 (5.8%) were positive (group 2: 79; group 3: 12, group 4: 9). In groups 2 and 3, 19 TCCs required antibiotic lock therapy (ALT). In group 4, all patients received intravenous therapy and ALT. Under this protocol, there were 0.27 episodes of CRBSI per 1,000 catheter days compared with 1.65 (P < .001) prior to its implementation. CONCLUSION: SCs based on easily accessible samples proved useful in triaging HD patients at a high risk of infection.
Assuntos
Bactérias/isolamento & purificação , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Monitoramento Epidemiológico , Diálise Renal/efeitos adversos , Antibacterianos/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Estudos ProspectivosRESUMO
OBJECTIVES: Limited data exist regarding the role of agr dysfunction in reducing susceptibility to vancomycin in methicillin-susceptible Staphylococcus aureus (MSSA). This study investigated the clinical and molecular epidemiology of MSSA causing bacteraemia, with emphasis on the reduced susceptibility to vancomycin (RSV) phenotype (MIC ≥ 1.5 mg/L) and its relationship with agr dysfunction. METHODS: All MSSA bloodstream isolates obtained at our hospital during 2010 were analysed. Antimicrobial susceptibility was determined and time-kill experiments were performed for oxacillin. Multilocus sequence type and agr genotype were determined and DNA microarray analysis of virulence factors was performed. agr dysfunction was assessed phenotypically and by RT-PCR quantification of RNAIII. RESULTS: Of 84 MSSA, 55 (65.5%) exhibited the RSV phenotype, comprising 13 clonal complexes. agr II polymorphism was more prevalent in RSV than non-RSV isolates (41.8% versus 17.2%, P = 0.023) and average levels of RNAIII gene expression were higher in RSV than non-RSV isolates (ΔCt 4.05 ± 3.29 versus 1.5 ± 2.11, P = 0.005), implying greater agr dysfunction in RSV MSSA. CONCLUSIONS: We demonstrated a correlation between RSV phenotype in MSSA and reduced agr expression, particularly in association with the agr II genotype. These results may help to understand the role of agr dysfunction in the increased mortality in MSSA infections.
Assuntos
Bacteriemia/epidemiologia , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Transativadores/metabolismo , Vancomicina/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Masculino , Análise em Microsséries , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Polimorfismo Genético , Estudos Retrospectivos , Espanha/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Análise de Sobrevida , Transativadores/genética , Fatores de Virulência/genéticaRESUMO
The title compound, C(14)H(19)NO(5)S, was prepared by nucleophilic addition of the lithium derivative of methyl-phenyl-sulfone to (3S,4R)-3,4-isopropyl-idene-dioxy-pyrroline 1-oxide. There are four mol-ecules in the asymmetric unit. The crystal structure determination confirms the configuration of the chiral centres as 2R,3S,4R. In the crystal, pairs of O-Hâ¯N hydrogen bonds link the mol-ecules into dimers.
RESUMO
Sulfonamides derived from 8-aminoquinoline react with Mn(II) and Mn(III) salts to form Mn(II) complexes; the Mn(III) species are reduced to the divalent state in the presence of 1,10 phenanthroline and bipyridine. Their molecular structure, determined by single crystal X-ray diffraction, show that all the complexes present a distorted octahedral geometry, in which the deprotonated sulfonamide acts as a bidentate ligand. UV-visible spectroscopy and changes in the melting temperature (Tm) of calf thymus DNA show a strong interaction of these complexes with DNA. The significant hypochromicity of the charge transfer transition at 370 nm without an appreciable change in wavelength and the minor changes in the relative viscosity of calf thymus DNA have been attributed to an interaction between the surface of DNA and the complexes. [Mn(qbsa)(2)(MeOH)(2)], [Mn(qbsa)(2)(phen)], [Mn(qtsa)(2)(H(2)O)(2)] and [Mn(qtsa)(2)(phen)] (where qbsa=N-quinolin-8-yl-bencenesulfonamide, qtsa=N-quinolin-8-yl-p-toluenesulfonamide and qnsa=N-quinolin-8-yl-naftalenesulfonamide) exhibit a prominent nuclease activity and the mechanism of DNA cleavage is investigated.
Assuntos
DNA/química , Desoxirribonucleases/química , Desoxirribonucleases/síntese química , Manganês/química , Plasmídeos/química , Sulfonamidas/química , Animais , Bovinos , Estrutura MolecularRESUMO
The annual incidence of Serratia marcescens bacteremia in a neonatal intensive care unit increased significantly between 2002 and 2010. Molecular epidemiology studies revealed that 8 clones were responsible for 85.2% of cases. Given that these infections are potentially preventable, even the appearance of 1 case of bacteremia should be an indicator for outbreak management.
Assuntos
Bacteriemia/epidemiologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Unidades de Terapia Intensiva Neonatal , Infecções por Serratia/epidemiologia , Serratia marcescens/classificação , Serratia marcescens/genética , Bacteriemia/microbiologia , Análise por Conglomerados , Infecção Hospitalar/microbiologia , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Epidemiologia Molecular , Infecções por Serratia/microbiologia , Serratia marcescens/isolamento & purificaçãoRESUMO
A total of 183 patients were colonized or infected with multidrug-resistant Pseudomonas aeruginosa isolates at a hospital in Spain during 2007-2010; prevalence increased over this period from 2.8% to 15.3%. To characterize these isolates, we performed molecular epidemiologic and drug resistance analysis. Genotyping showed that 104 (56.8%) isolates belonged to a single major clone (clone B), which was identified by multilocus sequence typing as sequence type (ST) 175. This clone was initially isolated from 5 patients in 2008, and then isolated from 23 patients in 2009 and 76 patients in 2010. PCR analysis of clone B isolates identified the bla(VIM-2) gene in all but 1 isolate, which harbored bla(IMP-22). ST175 isolates were susceptible to only amikacin (75%) and colistin (100%). Emergence of the ST175 clone represents a major health problem because it compromises therapy for treatment of P. aeruginosa nosocomial infections.