RESUMEN
A photocatalyzed ortho-alkylation of pyridine N-oxide with ynamides and arylacetylenes has been developed, which yields a series of α-(2-pyridinyl) benzyl amides/ketones. Mechanistic studies, including electrochemical studies, radical-trapping experiments, and Stern-Volmer fluorescence quenching studies demonstrate that pyridine N-oxide serves as both a redox auxiliary and radical acceptor to achieve the mild photocatalytic single-electron oxidation of carbon-carbon triple bonds with the generation of a cationic vinyl radical intermediate.
RESUMEN
The trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed reaction of methyl 6-hydroxyhexanoate with 3-O-benzyl-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-levulinoyl-α-d-mannopyranosyl trichloroacetimidate followed by a two-step deprotection (hydrogenolysis over Pd/C catalyst and Zemplén deacylation, to simultaneously remove the acetyl and levulinoyl groups) gave 5-(methoxycarbonyl)pentyl 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-α-D-mannopyranoside. The structure of the latter, for which crystals were obtained in the analytically pure state for the first time, followed from its NMR and high-resolution mass spectra and was confirmed by X-ray crystallography. The molecule has two approximately linear components; a line through the aglycon intersects a line through the mannosyl and tetronylamido groups at 120°. The crystal packing separates the aglycon groups from the tetronylamido and mannosyl groups, with only C-H...O hydrogen bonding among the aglycon groups and N-H...O, O-H...O and C-H...O links among the tetronylamido and mannosyl groups. A carbonyl oxygen atom accepts the strongest O-H...O hydrogen bond and two strong C-H...O hydrogen bonds. The geometric properties were compared with those of related molecules.
Asunto(s)
Manósidos/síntesis química , Antígenos O/química , Vibrio cholerae O1/metabolismo , Secuencia de Carbohidratos , Cristalografía por Rayos X , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Manósidos/química , Vibrio cholerae O1/químicaRESUMEN
A series of 3-aryl-3-arylmethoxy-azetidines were synthesized and evaluated for binding affinities at dopamine and serotonin transporters. The 3-aryl-3-arylmethoxyazetidines were generally SERT selective with the dichloro substituted congener 7c (Ki=1.0 nM) and the tetrachloro substituted derivative 7i (Ki=1.3 nM) possessing low nanomolar affinity for the SERT. The 3-(3,4-dichlorophenyl-3-phenylmethoxyazetidine (7g) exhibited moderate affinity at both DAT and SERT transporters and suggests that substitution of the aryl rings can be used to tune the mononamine transporter affinity.
Asunto(s)
Azetidinas/química , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/química , Proteínas de Transporte de Serotonina en la Membrana Plasmática/química , Azetidinas/síntesis química , Azetidinas/metabolismo , Cristalografía por Rayos X , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Cinética , Ligandos , Conformación Molecular , Unión Proteica , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Relación Estructura-ActividadRESUMEN
Di(phenylpropylamino)gossypol [systematic name: 2,2'-bis{1,6-dihydroxy-5-isopropyl-8-[(3-phenylpropylamino)methylidene]naphthalen-7-one}, C48H52N2O6, was formed by reaction of the dimeric natural product gossypol with 3-phenylpropylamine. The structure of this compound has its two naphthalene ring systems oriented approximately perpendicular to each other, and the two pendant phenylpropyl groups have different conformations. One of these side groups is considerably disordered at room temperature but less so at 120 K. The enantiomeric molecules form centrosymmetric dimers that are supported by intermolecular hydrogen bonds and by hydrophobic interactions between a pair of naphthalene rings. Two additional hydrogen bonds tie the dimer pairs into layers. Unlike gossypol and many gossypol Schiff base derivatives, the title compound crystallizes without the inclusion of solvent, which appears to occur because of the size and flexibility of its phenylpropyl pendent groups.
Asunto(s)
Productos Biológicos/química , Gosipol/química , Naftalenos/química , Propilaminas/química , Bases de Schiff/química , Solventes/química , Cristalografía por Rayos X , Gosipol/análogos & derivados , Enlace de Hidrógeno , Modelos Moleculares , Estructura Molecular , EstereoisomerismoRESUMEN
Invasive fungal infections are a major complication for individuals with compromised immune systems. One of the most significant challenges in the treatment of invasive fungal infections is the increased resistance of many organisms to widely used antifungals, making the development of novel antifungal agents essential. Many naturally occurring products have been found to be effective antimicrobial agents. In particular, saponins with spirostane glycosidic moieties-isolated from plant or marine species-have been shown to possess a range of antimicrobial properties. In this report, we outline a novel approach to the synthesis of a number of functionalized spirostane molecules that can be further used as building blocks for novel spirostane-linked glycosides and present results from the in vitro screenings of the antifungal potential of each derivative against four fungal species, including Candida albicans, Cryptococcus neoformans, Candida glabrata, and the filamentous fungus Aspergillus fumigatus.
Asunto(s)
Antifúngicos/síntesis química , Antifúngicos/farmacología , Hongos/efectos de los fármacos , Espirostanos/síntesis química , Espirostanos/farmacología , Antifúngicos/química , Aspergillus fumigatus/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candida glabrata/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacos , Isomerismo , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Espirostanos/químicaRESUMEN
6,6'-Dimethoxygossypolone (systematic name: 7,7'-dihydroxy-5,5'-diisopropyl-6,6'-dimethoxy-3,3'-dimethyl-1,1',4,4'-tetraoxo-2,2'-binaphthalene-8,8'-dicarbaldehyde), C(32)H(30)O(10), is a dimeric molecule formed by oxidation of 6,6'-dimethoxygossypol. When crystallized from acetone, 6,6'-dimethoxygossypolone has monoclinic (P2(1)/c) symmetry, and there are two molecules within the asymmetric unit. Of the four independent quinoid rings, three display flattened boat conformations and one displays a flattened chair/half-chair conformation. The angles between the planes of the two bridged naphthoquinone structures are fairly acute, with values of about 68 and 69°. The structure has several intramolecular O-H...O and C-H...O hydrogen bonds and several weak intermolecular C-H...O hydrogen bonds, but no intermolecular O-H...O hydrogen bonds.
Asunto(s)
Naftalenos/química , Cristalografía por Rayos X , Enlace de Hidrógeno , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Oxidación-Reducción , EstereoisomerismoRESUMEN
A series of 4-alkoxycarbonyl-1,5-diaryl-1,2,3-triazoles were synthesized regioselectively using click chemistry and evaluated at CB1 cannabinoid receptors. The n-propyl ester 11 (K(i)=4.6 nM) and phenyl ester 14 (K(i)=11 nM) exhibited the most potent affinity of the series.
Asunto(s)
Química Farmacéutica/métodos , Regulación de la Expresión Génica , Receptor Cannabinoide CB1/metabolismo , Triazoles/antagonistas & inhibidores , Triazoles/síntesis química , Sistema Nervioso Central/metabolismo , Diseño de Fármacos , Ésteres , Humanos , Cinética , Ligandos , Modelos Químicos , Modelos Moleculares , Conformación Molecular , Unión Proteica , Pirazoles/químicaRESUMEN
A series of 3-arylnortrop-2-enes and 3alpha-arylmethoxy-3beta-arylnortropanes were synthesized and evaluated for binding affinity at monoamine transporters. The 3-(3,4-dichlorophenyl)nortrop-2-ene (6e) exhibited high affinity for the SERT (K(i)=0.3 nM). The 3alpha-arylmethoxy-3beta-arylnortropanes were generally SERT selective with the 3alpha-(3.4-dichlorophenylmethoxy)-3betaphenylnortrop-2-ene (7c) possessing subnanomolar potency (K(i)=0.061 nM). However, 3alpha-(3,4-dichlorophenylmethoxy)-3beta-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT K(i)=22 nM), (SERT K(i)=6 nM) and (NET K(i)=101 nM)].
Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Nortropanos/química , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Nortropanos/síntesis química , Nortropanos/metabolismoRESUMEN
In the title compound, C(15)H(12)N(2)O(5)S, the benzisothia-zole group is approximately planar (r.m.s. deviation excluding H atoms and the two O atoms bonded to S = 0.023â Å). The dihedral angle between the benzisothia-zole ring and the terminal phenol ring is 84.9â (1)°. In the crystal, mol-ecules are joined by N-Hâ¯O and O-Hâ¯O hydrogen bonds, and π-stacking inter-actions are observed between alternating phenol and benzisothia-zole rings [centroid-centroid distances = 3.929â (3) and 3.943â (3)â Å].
RESUMEN
Synthesis of the upstream terminal hexasaccharide part of the lipopolysaccharides (LPS) of Vibrio cholerae O1, serotype Inaba has been improved. The key improvements include but are not limited to optimized conditions for the stereoselectivity of glycosylation reactions involved and fewer number of synthetic steps, compared to previous approaches. Particularly noteworthy is conducting the glycosylation of the very reactive glycosyl acceptor 8-azido-3,6-dioxaoctanol with the fully assembled hexasaccharide trichloroacetimidate under thermodynamic control. It produced the desired α glycoside with an α:ß ratio of 7:1, compared with the ratio of 1.1:1, observed when the coupling was conducted conventionally. Several substances, which were previously obtained in purity acceptable only for synthetic intermediates, were now obtained in the analytically pure state and were fully characterized. The structure of the key trisaccharide glycosyl acceptor was confirmed by single-crystal x-ray structure determination.
RESUMEN
A latent catalyst for the [3+2] cycloaddition reaction of azides and alkynes has been developed in accordance with the principles of Click chemistry.
Asunto(s)
Cobre/química , Compuestos Heterocíclicos/química , Metano/análogos & derivados , Compuestos Organometálicos/química , Triazoles/síntesis química , Acetileno/análogos & derivados , Acetileno/química , Azidas/química , Catálisis , Cristalografía por Rayos X , Ciclización , Compuestos Heterocíclicos/síntesis química , Imidazolidinas/química , Metano/química , Modelos Moleculares , Estructura Molecular , Estereoisomerismo , Triazoles/químicaRESUMEN
The crystal structure of beta-maltose octapropanoate (1) was solved to improve understanding of di-, oligo-, and polysaccharide conformations. The O6 and O6' atoms are in gg and gt orientations, respectively. Extrapolation of the coordinates of the non-reducing residue and observed linkage bond and torsion angles of 1 [Formula: see text] yields a left-handed helix similar to amylose triacetate I. The phi and psi values of 1 are also similar to those of other crystalline, acylated maltose compounds as well as some hydroxyl-bearing molecules. Acylated maltose moieties are often stabilized by stacking of the carbonyl groups and alpha-carbons on O3 and O2' as well as by the exo-anomeric effect. The conformation of 1 is within the 1-kcal/mol contour on a hybrid energy map built with a dielectric constant of 7.5, but corresponds to higher energies on maps made with lower dielectric constants. In one region of phi,psi space, both hydroxyl-bearing and derivatized maltose moieties are found but no inter-residue, intramolecular hydrogen-bonding occurs. In another region, only hydroxyl-bearing molecules crystallize and O2'...O3 hydrogen bonds are always found. In agreement with the energy surfaces, amylose helices extrapolated from available linkage geometries were almost all left-handed.
Asunto(s)
Cristalografía por Rayos X/métodos , Maltosa/química , Conformación de Carbohidratos , Cristalización , Enlace de Hidrógeno , Maltosa/análogos & derivados , Modelos Moleculares , Estructura MolecularRESUMEN
The use of N-heterocyclic carbene (NHC) as a ligand in the gold(I)-catalyzed cycloisomerization of enyne results in the assembly of a new carbocyclic product.
RESUMEN
A number of cationic gold(I) complexes have been synthesized and found to be stabilized by the use of N-heterocyclic carbene ligands. These species are often employed as in situ-generated reactive intermediates in gold catalyzed organic transformations. An isolated, well-defined species was tested in gold-mediated carbene transfer reactions from ethyl diazoacetate.
Asunto(s)
Oro/química , Compuestos Heterocíclicos/síntesis química , Metano/análogos & derivados , Catálisis , Compuestos de Diazonio/química , Compuestos Heterocíclicos/química , Hidrocarburos/síntesis química , Hidrocarburos/química , Metano/síntesis química , Metano/química , Modelos Químicos , Estructura MolecularRESUMEN
Recently, a one-chain monoclinic unit cell for cellulose III(I) having P2(1) symmetry and a single glucose in the asymmetric unit was proposed, based on high-resolution diffraction patterns. The new work challenged a two-chain structure that was published 25 years earlier, although it did not provide new three-dimensional coordinates. Our goals were to solve the structure by modeling, find whether modeling would reject the previously determined two-chain unit cell, and compare the model with the anticipated experimental structure. Combinations of three rotamers of the O-2, O-3, and O-6 hydroxyl groups produced 27 'up' and 27 'down' starting structures. Clusters ('minicrystals') of 13 cellotetraose chains terminated by methyl groups for each of the 54 starting structures were optimized with MM3(96). Hydroxyl groups on 16 of these 54 structures reoriented to give very similar hydrogen-bonding schemes in the interiors, along with the lowest energies. Hydrogen bonds included the usual intramolecular O-3H...O-5' linkage, with O-6' also accepting from O-3H. Interchain hydrogen bonds form an infinite, cooperative O-6H...O-2H...O-6 network. Direct comparison of total minicrystal energies for the one- and two-chain unit cell was inappropriate because the two-chain cell's alternate chains are shifted 0.9 A along the z-axis. To get comparable energy values, models were built with both cellotetraose and cellohexaose chains. The differences in their energies represent the energies for the central layers of cellobiose units. The one-chain cell models had much lower energy. The eight best 'up' one-chain models agree reasonably well with the structure newly determined by experiment.
Asunto(s)
Celulosa/química , Conformación de Carbohidratos , Simulación por Computador , Cristalización , Enlace de HidrógenoRESUMEN
A new series of N-arylalkyl-substituted 7-azabicyclo[2.2.1]heptanes and N-aryl-substituted 7-azabicyclo[2.2.1]heptanes were synthesized and evaluated as potential ligands for neuronal nicotinic acetylcholine receptors. The in vitro binding affinities (K(i)) of the 7-azabicyclo[2.2.1]heptane derivatives were measured by inhibition of [(3)H]cytisine binding to rat brain tissue. The most potent ligand of the series was found to be N-(3-pyridylmethyl)-7-azabicyclo[2.2.1]heptane (5b, K(i) = 98 nM). The chloro analogue (5a, K(i) = 245 nM) 5a and epibatidine (1) produced dose-dependent analgesia in both hotplate and tail-flick tests when administered subcutaneously. However, when compounds 1 and 5a,b were administered intrathecally, all produced analgesia in the tail-flick test but only 5a produced analgesia in the hotplate test.
Asunto(s)
Analgésicos no Narcóticos/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Agonistas Nicotínicos/síntesis química , Piridinas/química , Receptores Nicotínicos/metabolismo , Analgésicos no Narcóticos/química , Analgésicos no Narcóticos/farmacología , Animales , Temperatura Corporal/efectos de los fármacos , Encéfalo/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Cristalografía por Rayos X , Dopamina/metabolismo , Técnicas In Vitro , Inyecciones Espinales , Ligandos , Ratones , Agonistas Nicotínicos/química , Agonistas Nicotínicos/farmacología , Dimensión del Dolor , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Relación Estructura-ActividadRESUMEN
[reaction: see text] The synthesis and characterization of [Pd(IPr)Cl(2)](2) (1), an air- and moisture-stable complex, is reported. The utilization of 1 as a catalyst for amination of aryl chlorides and bromides with a variety of amine coupling partners under mild conditions is described. The amination reactions with 1 show a remarkable insensitivity to oxygen and water, and thus the amination reactions could be performed in air on the benchtop with undried reagent grade solvents and substrates with small effects on reaction times and conversions.
RESUMEN
[reaction: see text] In the study of the barbituric acid initiated 2,2'-pyridil rearrangement, a very efficient synthetic procedure (isolated yield 80-90%) for the preparation of useful 2-pyrilidenes 3 was developed.
Asunto(s)
Barbitúricos/química , Barbitúricos/síntesis química , Cristalografía por Rayos X , Enlace de Hidrógeno , Iones , Cinética , Espectroscopía de Resonancia Magnética , Estructura Molecular , Piridinas/químicaRESUMEN
Palladacycle dimers possessing bridging halides can be easily cleaved by using N-heterocyclic carbenes (NHCs) to generate novel monomeric complexes. The structure of one of these was determined by single-crystal diffraction study and consists of a square-planar coordination around the palladium center where the NHC ligand is trans to the amine of the palladacycle. The complex was found to be equally active in aryl amination and alpha-arylation of ketones even at very low catalyst loading (0.02 mol %). Primary and secondary alkyl/arylamines are equally active partners in coupling reactions. [reaction: see text]
RESUMEN
The reactivity of a N-heterocyclic carbene (NHC) with a pseudo-acid (ester in this case) is described. The product results from an unusual C-H bond activation. The structure of the product has been established by a single crystal diffraction study.