RESUMEN
We investigated the photophysical properties of difluoroboronated ß-diketones (BF2DK) with chrysene and pyrene skeletons (ChB and PyB, respectively) in solution and in the solid state. Acetylchrysenes, as the key precursors to ChBs, were photochemically prepared from the corresponding (acetylphenyl)naphthylethenes by means of a modified photocyclization method. The absorption and emission spectra of the BF2DKs were obtained in chloroform and acetonitrile, and the quantum yields and lifetimes of the fluorescence were determined. Excimeric fluorescence from PyB was absent even in highly concentrated solution. Based on the Lippert-Mataga analysis of the absorption and fluorescence features, the photophysical properties of the ChBs were discussed in comparison with those of PyB. The fluorescence states of the studied BF2DKs are shown to be of a charge-transfer character. The fluorescence quantum yields decrease with increasing the solvent polarity due to the enhanced internal conversion process. The fluorescence quantum yields in the solid state of the studied BF2DKs were determined, and it was found that PyB is fluorescent, whereas the fluorescence quantum yields of the ChBs depend on the substituted position of the chrysene moiety.
Asunto(s)
Crisenos/química , Pirenos/química , Acetonitrilos/química , Crisenos/síntesis química , Ciclización , Pirenos/síntesis química , Teoría Cuántica , Solventes/química , Espectrometría de Fluorescencia , Difracción de Rayos XRESUMEN
A tandem one-pot method for the direct synthesis of polysubstituted triphenylene 2,3-dicarboxylic esters with different substitution patterns was developed by enyne metathesis of diarylacetylene, followed by Diels-Alder, aromatization and a cyclization cascade.
Asunto(s)
Alquinos/química , Crisenos/síntesis química , Ácidos Dicarboxílicos/química , Crisenos/química , Ésteres , Estructura MolecularRESUMEN
Chiral polycyclic aromatic hydrocarbons containing bis(1-adamantyl) groups at the peri-positions, named equatorenes, were synthesized in optically pure form starting from optically pure 4,5-bis(1-adamantyl)-8-methoxy-1-naphthol. A sequential Diels-Alder reaction of furan and arynes generated from 1,2-bromotriflates provided tricyclic and tetracyclic epoxides, and acid-catalyzed aromatization gave phenanthrol and chrysenol. Deoxygenation reactions involving the hydrogenolysis of triflates gave 1,8-bis(1-adamantyl)naphthalene, 1,10-bis(1-adamantyl)phenanthrene, and 1,12-bis(1-adamantyl)chrysene. 3,4-Bis(1-adamantyl)pyrene was synthesized from phenanthrol by Sonogashira coupling and Pt-catalyzed cyclization. Essentially no racemization occurred during the synthesis. X-ray analysis indicated the distorted naphthalene moiety possessing the peri-diadamantyl groups and the flat structure of the other benzene rings. UV-vis analysis of the equatorenes showed considerable redshifts compared with that of the corresponding achiral arenes. Electrochemical analysis of the naphthalene and pyrene indicated that the distortion decreased the highest occupied molecular orbital stability with no marked effect on the lowest unoccupied molecular orbital energy level, and the origin was discussed on the basis of calculation results.
Asunto(s)
Adamantano/química , Crisenos/química , Naftalenos/química , Fenantrenos/química , Pirenos/química , Crisenos/síntesis química , Modelos Moleculares , Estructura Molecular , Naftalenos/síntesis química , Fenantrenos/síntesis química , Pirenos/síntesis químicaRESUMEN
The convenient synthesis of substituted triphenylenes and azatriphenylenes has been achieved by the cationic rhodium(I)/H8-BINAP or BINAP complex-catalyzed [2 + 2 + 2] cycloaddition under mild conditions. Photophysical properties of representative triphenylenes and azatriphenylenes were examined, which revealed that azatriphenylenes showed higher fluorescence quantum yields than triphenylenes. This method was successfully applied to the synthesis of highly fluorescent triphenylene-based long ladder molecules.
Asunto(s)
Crisenos/síntesis química , Naftalenos/química , Rodio/química , Catálisis , Reacción de Cicloadición , Fluorescencia , Estructura Molecular , Espectrometría de Fluorescencia , EstereoisomerismoRESUMEN
Herein, we report the development of a new method for the syntheses of substituted triphenylenes from the corresponding 1,2,4-trisubstituted arenes, which were themselves generated in a highly regioselective manner according to an intermolecular alkyne cyclotrimerization reaction that was catalyzed by a novel Co-TMTU complex. This highly regioselective reaction for the formation of 1,2,4-trisubstituted arenes will be a valuable addition to the plethora of tools already available to synthetic chemists and encourage further mechanistic studies of this important alkyne trimerization process.
Asunto(s)
Alquinos/química , Crisenos/síntesis química , Cobalto/química , Catálisis , Crisenos/química , Ciclización , Estructura Molecular , EstereoisomerismoRESUMEN
An efficient, new, and scalable semisynthesis of glucan synthase inhibitors 1 and 2 from the fermentation product enfumafungin 3 is described. The highlights of the synthesis include a high-yielding ether bond-forming reaction between a bulky sulfamidate 17 and alcohol 4 and a remarkably chemoselective, improved palladium(II)-mediated Corey-Yu allylic oxidation at the highly congested C-12 position of the enfumafungin core. Multi-hundred gram quantities of the target drug candidates 1 and 2 were prepared, in 12 linear steps with 25% isolated yield and 13 linear steps with 22% isolated yield, respectively.
Asunto(s)
Alcoholes/química , Antifúngicos/síntesis química , Antifúngicos/farmacología , Crisenos/química , Crisenos/síntesis química , Equinocandinas/química , Glucosiltransferasas/antagonistas & inhibidores , Glicósidos/química , Paladio/química , Triterpenos/química , Catálisis , Estructura Molecular , EstereoisomerismoRESUMEN
The zinc complex of a new triphenylene based receptor is evaluated for its anti-oxidant activity which is better in comparison to that of commercially available anti-oxidants.
Asunto(s)
Antioxidantes/química , Crisenos/química , Zinc/química , Antioxidantes/síntesis química , Crisenos/síntesis química , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Oxidación-ReducciónAsunto(s)
Carcinógenos Ambientales/toxicidad , Contaminantes Ambientales/toxicidad , Neoplasias/inducido químicamente , Hidrocarburos Policíclicos Aromáticos/toxicidad , Acridinas/síntesis química , Acridinas/química , Acridinas/toxicidad , Animales , Benzo(a)Antracenos/síntesis química , Benzo(a)Antracenos/química , Benzo(a)Antracenos/toxicidad , Benzo(a)pireno/síntesis química , Benzo(a)pireno/química , Benzo(a)pireno/toxicidad , Benzopirenos/síntesis química , Benzopirenos/química , Benzopirenos/toxicidad , Carbazoles/síntesis química , Carbazoles/química , Carbazoles/toxicidad , Carcinógenos Ambientales/síntesis química , Carcinógenos Ambientales/química , Crisenos/síntesis química , Crisenos/química , Crisenos/toxicidad , Contaminantes Ambientales/síntesis química , Contaminantes Ambientales/química , Fluorenos/síntesis química , Fluorenos/química , Fluorenos/toxicidad , Humanos , Hidrocarburos Policíclicos Aromáticos/síntesis química , Hidrocarburos Policíclicos Aromáticos/química , Pirenos/síntesis química , Pirenos/química , Pirenos/toxicidadRESUMEN
Triphenylene has been successfully fused to the porphyrin periphery through a convenient oxidative ring-closure reaction. Bistriphenylene-fused porphyrins and a dibenzo[fg,op]tetracene-fused porphyrin have also been obtained using a similar approach. These π-extended porphyrins exhibited broadened and bathochromic shifted UV-vis absorptions.
Asunto(s)
Crisenos/síntesis química , Modelos Moleculares , Porfirinas/síntesis química , Catálisis , Crisenos/química , Estructura Molecular , Paladio/química , Porfirinas/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Expansion of the D-ring of 19-norsteroids with incorporation of the steroid C-18 methyl group into a newly formed six-membered ring provides easy access to the chrysene ring system. By taking advantage of the symmetry of the chrysene ring system and avoiding meso chrysene intermediates, four optically pure 2,8-difunctionalized (C-2 hydroxyl group and C-8 oxo group) hexadecahydrochrysene diastereomers, and their corresponding optically pure enantiomers were prepared from 19-nortestosterone. The eight chrysene stereoisomers are of interest as starting materials for preparing chrysene analogues of physiologically important neurosteroids.
Asunto(s)
Química Farmacéutica/métodos , Crisenos/síntesis química , Agonistas del GABA/síntesis química , Antagonistas del GABA/síntesis química , Nandrolona/química , Neurotransmisores/síntesis química , Andrógenos/química , Cromatografía en Capa Delgada , Crisenos/análisis , Agonistas del GABA/análisis , Antagonistas del GABA/análisis , Humanos , Espectroscopía de Resonancia Magnética , Neurotransmisores/análisis , Pregnanos/química , Receptores de GABA/metabolismo , EstereoisomerismoRESUMEN
A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure-activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinoline-based antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting ß-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.
Asunto(s)
Antibacterianos/síntesis química , Antimaláricos/síntesis química , Antivirales/síntesis química , Toxinas Botulínicas Tipo A/antagonistas & inhibidores , Crisenos/síntesis química , Ebolavirus/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Quinolinas/síntesis química , Animales , Anopheles/parasitología , Antibacterianos/química , Antibacterianos/farmacología , Antimaláricos/química , Antimaláricos/farmacología , Antivirales/química , Antivirales/farmacología , Línea Celular , Chlorocebus aethiops , Crisenos/química , Crisenos/farmacología , Hemoproteínas/antagonistas & inhibidores , Malaria/tratamiento farmacológico , Ratones , Modelos Moleculares , Plasmodium berghei , Quinolinas/química , Quinolinas/farmacología , Ratas , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
This paper reports the self-assembling and electrochemical nature of hexaazatriphenylene-based electron-deficient heteroaromatics with an expanded π-electron system. The tri(phenanthro)hexaazatriphenylenes (TPHAT-Cs) and tri(phenanthrolino)hexaazatriphenylenes (TPHAT-Ns) were prepared by condensation reactions of the corresponding phenanthrenequinones and phenanthrolinediones, respectively, with hexaaminobenzene. Their electron affinity was indicated from cyclic voltammetry measurements, in which the first reduction potentials were evaluated at around -1.7 V (vs Fc/Fc(+)) in dichloromethane. In nonpolar and polar solvents and in the film state, the TPHAT-Cs and TPHAT-Ns formed one-dimensional aggregates with an H-type parallel stacking mode. In the MALDI-TOF mass spectra, significant peaks were seen at several multiples of the parent ion up to tetramer aggregates. The (1)H NMR spectra indicated a line-broadening effect due to the aggregation. The UV-vis and fluorescence spectra showed a concentration dependence, which is attributed to a dynamic exchange between the monomer and aggregate species. The order of the aggregative nature was estimated from the concentration dependence and the fluorescence quantum yield. By replacement of the peripheral aromatic moieties instead of the phenanthrene (TPHAT-Cs) with the phenanthroline (TPHAT-Ns), the aggregative nature was enhanced.
Asunto(s)
Compuestos Aza/síntesis química , Crisenos/síntesis química , Compuestos Aza/química , Crisenos/química , Electroquímica , Electrones , Microscopía de Fuerza Atómica , Estructura Molecular , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , EstereoisomerismoRESUMEN
We describe herein the synthesis of novel 6,12-distributed chrysene as potent anticancer agents. In vitro and in vivo studies are also reported here.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/uso terapéutico , Crisenos/química , Crisenos/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Crisenos/síntesis química , Crisenos/farmacología , Femenino , Humanos , RatonesRESUMEN
A convergent and flexible synthesis of substituted triphenylenes, azatriphenylenes, and the cytotoxic alkaloids dehydrotylophorine and tylophorine has been developed.
Asunto(s)
Alcaloides/síntesis química , Compuestos Aza/síntesis química , Crisenos/síntesis química , Indolizinas/síntesis química , Fenantrenos/síntesis química , Alcaloides/química , Alcaloides/efectos de la radiación , Compuestos Aza/química , Compuestos Aza/efectos de la radiación , Crisenos/química , Crisenos/efectos de la radiación , Ciclización , Indolizinas/química , Indolizinas/efectos de la radiación , Microondas , Estructura Molecular , Fenantrenos/química , Fenantrenos/efectos de la radiación , EstereoisomerismoRESUMEN
The title compound, 1-Hex, was synthesized by the Zr-mediated biphenylation of 4,4'-dihexyloctabromobiphenyl using (Li(THF)4)2 x Zr(biphe)3, where biphe is the 2,2'-biphenyldiyl ligand, in 5% isolated yield. Two independent X-ray diffraction analyses revealed that arene 1-Hex possesses a highly strained and hindered aryl-aryl single bond. This bond causes the phenanthro[9,10-b]triphenylene (PTP) moieties to twist (anthracene subunit dihedral, 69 degrees); the interlocked, helical, homochiral PTP moieties give rise to effective D2 symmetry. The calculated adiabatic homolytic bond dissociation energy of this strained bond is only 67 kcal/mol, but nonetheless the bond exhibits a surprisingly normal length (1.49 A); the reason is elongation only slowly releases strain. Variable temperature NMR revealed two dynamic processes: hexyl rotation (12.0 +/- 0.4 kcal/mol) and inversion of chirality (15.2 +/- 0.6 kcal/mol). DFT calculations provide rate-determining transitions states, whose energies agree with measured values, and provide insight to the mechanism of these processes. Rotation about the central bond is not involved in either observed process. Calculations demonstrate that rotation does not involve a simple torsion of the equilibrium structure, but rather a complex movement with a barrier of 49 kcal/mol from a slipped-parallel, C(2h) intermediate.
Asunto(s)
Crisenos/química , Fenoles/química , Alquilación , Crisenos/síntesis química , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Molecular , Fenoles/síntesis química , Temperatura , Difracción de Rayos XRESUMEN
The first tetra-substituted non-fused chrysene, 3,6,9,12-tetrakis(4-tert-butylphenyl)chrysene with blue electroluminescence at 450 nm, and with a radiance of 500 cd m(-2), was synthesized by a two-step procedure: direct bromination of chrysene in trimethyl phosphate, followed by palladium-catalyzed cross-coupling of tetrabromochrysene and tert-butylphenylboronic acid .
Asunto(s)
Crisenos/química , Hidrocarburos Bromados/química , Crisenos/síntesis química , Cristalografía por Rayos X , Hidrocarburos Bromados/síntesis química , LuminiscenciaRESUMEN
Naphtho[8,1,2- ghi]chrysene, commonly known as naphtho[1,2- e]pyrene (N[1,2- e]P) is a widespread environmental pollutant, identified in coal tar extract, air borne particulate matter, marine sediment, cigarette smoke condensate, and vehicle exhaust. Herein, we determined the ability of rat liver microsomes to metabolize N[1,2- e]P and an unequivocal assignment of the metabolites by comparing them with independently synthesized standards. We developed the synthesis of both the fjord region and the K-region dihydrodiols and various phenolic derivatives for metabolite identification. The 12-OH-N[1,2- e]P, fjord region dihydrodiol 14 and diol epoxide 15 were synthesized using a Suzuki cross-coupling reaction followed by the appropriate manipulation of the functional groups. The K-region trans-4,5-dihydrodiol ( 18) was prepared by the treatment of N[1,2- e]P with OsO 4 to give cis-dihydrodiol 16, followed by pyridinium chlorochromate oxidation to quinone 17, and finally reduction with NaBH 4 to afford the dihydrodiol 18 with the desired trans stereochemistry. The 9-OH-N[1,2- e]P ( 30) and N[1,2- e]P trans-9,10-dihydrodiol ( 32) were also synthesized following a Suzuki cross-coupling approach starting from 1,2,3,6,7,8-hexahydropyrene-4-boronic acid. The metabolism of N[1,2- e]P with rat liver microsomes led to several dihydrodiol and phenolic metabolites as assessed by the HPLC trace. The 11,12-dihydrodiol and 4,5-dihydrodiol were identified as major dihydrodiol metabolites. The synthesized 9,10-dihydrodiol, on the other hand, did not match with any of the peaks in the metabolism trace. Among the phenols, only 12-OH-N[1,2- e]P was identified in the metabolism. The other phenolic derivatives synthesized, that is, the 4-/5-, 9-, 10-, and 11-hydroxy derivatives, were not detected in the metabolism trace. In summary, N[1,2- e]P trans-11,12-dihydrodiol was the major metabolite formed along with N[1,2- e]P 4,5- trans-dihydrodiol and 12-OH-N[1,2- e]P on exposure of rat liver microsomes to N[1,2- e]P. The presence of N[1,2- e]P in the environment and formation of fjord region dihydrodiol 14 as a major metabolite in in vitro metabolism studies strongly suggest the role of N[1,2- e]P as a potential health hazard.
Asunto(s)
Crisenos/síntesis química , Crisenos/metabolismo , Contaminantes Ambientales/química , Contaminantes Ambientales/metabolismo , Microsomas/metabolismo , Naftalenos/síntesis química , Naftalenos/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Ciclización , Espectroscopía de Resonancia Magnética , Masculino , Estructura Molecular , Ratas , Ratas Sprague-DawleyRESUMEN
A series of 5-benzylidene-1,2-dihydro-2,2,4-trimethyl-5H-1-aza-6-oxa-chrysenes was synthesized and profiled for their ability to act as selective glucocorticoid receptor modulators (SGRMs). The synthesis and structure-activity relationships for this series of compounds are presented.
Asunto(s)
Crisenos/farmacología , Receptores de Glucocorticoides/efectos de los fármacos , Crisenos/síntesis química , Crisenos/química , Relación Estructura-ActividadRESUMEN
The synthesis and spectroscopic properties of Cr(bpy)(chrySQ)(chryCat), a complex containing chromium(III) metal ion and chrysenequinone ligand in its partially reduced (chrySQ) and fully reduced (chryCat) forms, are described. The complex has been prepared by two different routes from Cr(CO)6 and Cr(chrySQ)3. Variable temperature magnetic susceptibility measurements indicated a strong antiferromagnetic coupling between Cr(III) (S=3/2) and chrysenesemiquinone radical (S=1/2), giving a magnetic coupling constant J=-342 cm(-1). Ligand-based redox couples were observed in the electrochemical studies that consist of quasi-reversible chrySQ/chryCat and bpy/bpy*- reductions and chryCat/chrySQ oxidation at negative potentials and irreversible chrySQ/chryBQ oxidation at positive potential. However, the metal was inert in the studied potential range. The electronic spectra of the complex revealed interesting properties. In addition to interaligand pi-pi* and n-pi* transitions, other bands corresponding to Cr(t(2g))-->chrySQ(pi*) and Cr(t(2g))-->bpy(pi*) metal-to-ligand charge-transfer MLCT transitions were observed. The infrared spectral analysis was informative in assigning the vibrations due to SQ and Cat ligands. Also, it was a useful tool in confirming the coordination of bpy ligand to chromium metal ion.
Asunto(s)
2,2'-Dipiridil/química , Catecoles/química , Cromo/química , Crisenos/síntesis química , Compuestos Organometálicos/química , Crisenos/química , Electrones , Ligandos , Espectrofotometría , Espectrofotometría Infrarroja , TemperaturaRESUMEN
Dibenzo[c,mno]chrysene commonly known as naphtho[1,2-a]pyrene (N[1,2-a]P) is an environmental pollutant, recently identified in coal tar extract, in air-borne particulate matter, in marine sediment, and in cigarette-smoke condensate. We recently reported an efficient synthesis of N[1,2-a]P and examined its in vitro metabolism by male Sprague Dawley rat liver S9 fraction, which resulted in a number of dihydrodiol and phenolic metabolites. The synthesis of 10-hydroxy-N[1,2-a]P and fjord region N[1,2-a]P trans-9,10-dihydrodiol, which were identified among the various metabolites, was assigned earlier by comparing with the synthetic standards. The other major metabolites were separated by HPLC and, based on the 1H NMR analysis, were tentatively suggested to be the two K-region dihydrodiols, that is, N[1,2-a]P trans-4,5-dihydrodiol (6) and N[1,2-a]P trans-7,8-dihydrodiol (7), and the hydroxy derivatives of N[1,2-a]P. To unequivocally assign the structure to each of the peaks and to have them in larger amounts for toxicological studies, we have now synthesized the two K-region dihydrodiols and the 1-/3-hydroxy-N[1,2-a]P, short-listed based on the proton NMR of the collected peaks. The K-region dihydrodiols 6 and 7 were prepared by the treatment of N[1,2-a]P with OsO(4) to give a mixture of cis dihydrodiols 2 and 3, followed by pyridinium chlorochromate-assisted oxidation to quinones 4 and 5, and finally reduction with NaBH(4) to afford the dihydrodiols 6 and 7 with the desired trans stereochemistry. The 1-hydroxy-N[1,2-a]P (22) and 3-hydroxy-N[1,2-a]P (23) were synthesized using a photochemical approach. As expected, all the synthesized dihydrodiol and phenolic derivatives of N[1,2-a]P identified with those obtained from in vitro metabolism enabling the assignment of all the major metabolites.