1,720,973 research outputs found
A simple and mild synthesis of a 4,5-cyclopropanated carbohydrate
Get PDFThe synthesis of a 4,5-cyclopropanated carbohydrate was achieved in five steps from methyl α-d-mannopyranoside under mild conditions that avoid the use of carbene chemistry.Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Spanevello, Rolando Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin
Recent advances in the solid-phase synthesis of N-heteroaromatic five membered rings
No full textCombinatorial chemistry and related high-speed syntheses are powerful tools for the discovery of new drugs. In particular, solid-phase organic synthesis (SPOS) is being widely used for the preparation of a large number of structurally diverse small organic molecules in order to accelerate lead generation and optimization. Due to their potential biological activities, the synthesis of five-membered ring heteroaromatics is of great importance in medicinal chemistry. Consequently, different solid-phase approaches for the preparation of these heterocycles have been recently introduced. This chapter covers the syntheses of N-heteroaromatic five-membered rings that have been reported in the literature during the last seven years.Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Poeylaut Palena, Andrés Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Mata, Ernesto Gabino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin
End-group differentiating ozonolysis of norbornene systems to access to highly substituted cyclopentane rings
Get PDFThe end-group-differentiating ozonolysis concept is discussed, with an emphasis on norbornene systems. Different remote functional groups in endo positions in norbornene derivatives are able to direct the primary ozonide fragmentation. By analysis of the factors affecting the regioselectivity, a rule to predict the direction of the primary ozonide rupture is formulated. These reactions give access to highly substituted cyclopentane rings and provide opportunities for their subsequent regioselective manipulation.Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Mangione, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Suarez, Alejandra Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: Spanevello, Rolando Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; Argentin
The non-metathetic role of Grubbs’ carbene complexes: From hydrogen-free reduction of α,β-unsaturated alkenes to solid-supported sequential cross-metathesis/reduction
Get PDFAn efficient and high-yielding “hydrogen-free” reduction of α,β-unsaturated alkenes was carried out employing Grubbs' catalyst in a non-metathetic role and Et3SiH. Conditions were optimized under microwave irradiation. Application to the solid-phase organic synthesis allows a facile construction of sp3–sp3 carbon bonds through a sequential cross metathesis/olefin reduction.Fil: Poeylaut Palena, Andrés Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Mata, Ernesto Gabino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin
The X-ray structure of carboxypeptidase a inhibited by a thiirane mechanism-based ihibitor
Get PDFThe three-dimensional X-ray crystal structure of carboxypeptidase A, a zinc-dependent hydrolase, covalently modified by a mechanism-based thiirane inactivator, 2-benzyl-3,4-epithiobutanoic acid, has been solved to 1.38 Å resolution. The interaction of the thiirane moiety of the inhibitor with the active site zinc ion promotes its covalent modification of Glu-270 with the attendant opening of the thiirane ring. The crystal structure determination at high resolution allowed for the clear visualization of the covalent ester bond to the glutamate side chain. The newly generated thiol from the inhibitor binds to the catalytic zinc ion in a monodentate manner, inducing a change in the zinc ion geometry and coordination, while its benzyl group fits into the S1' specificity pocket of the enzyme. The inhibitor molecule is distorted at the position of the carbon atom that is involved in the ester bond linkage on one side and the zinc coordination on the other. This particular type of thiirane-based metalloprotease inhibitor is for the first time analyzed in complex to the target protease at high resolution and may be used as a general model for zinc-dependent proteases.Fil: Fernández, Daniel. Universitat Autònoma de Barcelona; EspañaFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados UnidosFil: Vendrell, Josep. Universitat Autònoma de Barcelona; EspañaFil: Avilés, Francesc X.. Universitat Autònoma de Barcelona; EspañaFil: Mobashery, Shahriar. University of Notre Dame; Estados Unido
Metal-mediated synthesis of pyrrolines
Get PDFThe five-membered, nitrogen-containing pyrroline ring is a privileged structure. This ring is present in many bioactive compounds from natural sources. Pyrrolines - the dihydro derivatives of pyrroles - have three structural isomer classes, depending on the location of the double bond: 1-pyrrolines (3,4-dihydro-2H-pyrroles), 2-pyrrolines (2,3-dihydro-1H-pyrroles) and 3-pyrrolines (2,5-dihydro-1H-pyrroles). This review aims to describe the latest advances for the synthesis of pyrrolines by transition metal-catalyzed cyclizations. Only reactions in which the pyrroline ring is formed by metal promotion are described. Transformations of the pyrroline ring in other heterocycles, and the structural manipulations of the pyrroline itself are not discussed. The review is organized into three parts, each covering the metal-mediated synthesis of the three pyrroline isomers. Each part is subdivided according to the metal involved, and concludes with a brief description of notable biological activities within the class.Fil: Medran, Noelia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: la Venia, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin
Sintesis de fotosondas derivadas de ampicilina
No full textThe Gram-positive bacteria Staphylococcus aureus is the main cause of hospital- and community-associated infections. S. aureus is the most frequent cause of surgical, lower respiratory tract, and cardiovascular infections. In addition, it is the second most common cause of health-care associated pneumonia and of bloodstream infections.1,2,5 Methicillin-resistant S. aureus (MRSA) is a high priority concern in the world and in particular in Latin America, both in hospitals and in the community. MRSA has become the first cause of hospital-associated infections in Latin America, and there has been an increasing number of reports of community acquired MRSA infections. The acquisition of resistance to b-lactam antibiotics, generally concurrent with the acquisition of resistance to other antibacterial agents, represents a huge challenge for the prevention and treatment of S. aureus associated infections. Very few new antibacterial are in advanced stages of clinical evaluation for the treatment of bacterial infections, including MRSA. S. aureus presents two main mechanisms of resistance to b-lactam antibiotics: the expression of the PC1 b-lactamase, capable of hydrolyzing and inactivating the b-lactam antibiotics, and the acquisition of a PBP (PBP2a) with low affinity for b-lactam antibiotics, and which is hence not inhibited by them. S. aureus presents another important system that coordinates the response to antibiotics that inhibit the biosynthesis of the peptidoglycan: the VraSRT system. The three-component system VraSRT controls the peptidoglycan crosslinking process, and is activated by β-lactam and glycopeptide antibiotics. VraSRT has a critical role in glycopeptide-resistance. The VraSRT system is composed of three components: VraS and VraT are membrane proteins that could quickly detect stress in the cell wall and transmit the signal to the cell cytoplasm. The understanding of the signal transduction mechanism employed by the sensor proteins of the VraSRT system is of great interest because they are possible targets for the design of inhibitors that can be used in conjunction with antibiotics for the treatment of S. aureus infections. Photoaffinity labeling is a useful technique employed to study noncovalent interactions between protein-ligands and protein-protein complexes. A photoaffinity labeling reagent is a molecule that contains a photoreactive group which produces highly reactive intermediates upon photolysis. The most widely used classes of photoactive functionality include benzophenones, trifluoromethylphenyldiazirines, and arylazides, which give rise to diradicals, carbenes and nitrenes by UV irradiation. These generated intermediates can produce hydrogen abstraction reactions, initiate highly efficiency double bond addition reactions, insertion reactions to C-H and N-H bonds (carbenes, nitrenes) with neighboring biomolecules giving stable covalent adducts. Each of these families of compounds have advantages and disadvantages. For example, benzophenones are chemically more stable than azides and diazirines, can be manipulated in ambient light and like diazirines are activated at 350 nm avoiding wavelengths that cause protein damage. However, its bulky size and hydrophobicity can complicate the binding with the macromolecule. On the other hand, arylazides give reactions with high efficiency, present excellent stability for storage and their synthesis is easy but they are activated at wavelengths that could affect the biological system under study. Finally, trifluoromethylphenyldiazirines meet most of the characteristics of an ideal photoreactive, although their synthesis needs more steps. Herein, we report the synthesis of modified variants of β-lactam antibiotics that can be used as affinity photoprobes in order to elucidate the molecular events that lead to the induction of resistance systems in bacteria. Using these photoprobes we demonstrate that the membrane protein VraS interacts directly with β-lactam antibiotics, which results in its autophosphorylation and phosphotransfer to VraR.Fil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin
Gold-Catalyzed Cycloisomerization of Alkyne-Containing Amino Acids: Controlled Tuning of C–N vs. C–O Reactivity
Get PDFVersatile alkyne-containing amino acids were used as ambident precursors in the divergent synthesis of alkylidenelactones and 1-pyrrolines. Two gold-catalyzed protocols were applied for selective intramolecular O- and N-cycloisomerization reactions.Fil: Medran, Noelia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Villalba, Matias Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Mata, Ernesto Gabino. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin
The future of the β-lactams
Get PDFIn the 80 years since their discovery the β-lactam antibiotics have progressed through structural generations, each in response to the progressive evolution of bacterial resistance mechanisms. The generational progression was driven by the ingenious, but largely empirical, manipulation of structure by medicinal chemists. Nonetheless, the true creative force in these efforts was Nature, and as the discovery of new β-lactams from Nature has atrophied while at the same time multi-resistant and opportunistic bacterial pathogens have burgeoned, the time for empirical drug discovery has passed. We concisely summarize recent developments with respect to bacterial resistance, the identity of the new β-lactams, and the emerging non-empirical strategies that will ensure that this incredible class of antibiotics has a future.Fil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. University of Notre Dame; Estados UnidosFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados UnidosFil: Fisher, Jed F.. University of Notre Dame; Estados UnidosFil: Mobashery, Shahriar. University of Notre Dame; Estados Unido
Exploration of mild copper-mediated coupling of organotrifluoroborates in the synthesis of thiirane-based inhibitors of matrix metalloproteinases
Get PDFThe copper-mediated and non-basic oxidative cross-coupling of organotrifluoroborates with phenols was applied to elaboration of the structures of thiirane-based inhibitors of matrix metalloproteinases. By revision of the synthetic sequence to allow this cross-coupling as the final step, and taking advantage of the neutral nature of organotrifluoroborate cross-coupling, a focussed series of inhibitors showing aryloxy and alkenyloxy replacement of the phenoxy substituent was prepared. This reaction shows exceptional promise as an alternative to the classic copper-mediated but strongly basic Ullmann reaction, for the diversification of ether segments within base-labile lead structures.Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados UnidosFil: Bouley, Renee. University of Notre Dame; Estados UnidosFil: Fisher, Jed F.. University of Notre Dame; Estados UnidosFil: Chang, Mayland. University of Notre Dame; Estados UnidosFil: Mobashery, Shahriar. University of Notre Dame; Estados Unido
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