RESUMO
Under the catalysis of Pd(OAc)2/dppf/Na2CO3, the decarboxylative 1,4-addition reaction of benzofuran-based azadienes with allyl phenyl carbonates took place easily and delivered the desired products in reasonable chemical yields. The chemical structure of the target compounds was clearly identified by single crystal X-ray structural analysis.
RESUMO
Under the catalysis of Rh2(OAc)4 (10 mol%) and binapbisphosphine ligand (±)-L3 (20 mol%) in DCE at 80 °C, the cascade cyclization of diazoimides with alkylidenepyrazolones underwent stereoselectively (dr > 20:1), affording pyrazole-fused oxa-bridged oxazocines in reasonable chemical yields. The chemical structure and relative configuration of title products were firmly identified by X-ray diffraction analysis.
RESUMO
Eleven new compounds including five bisabolane (1-5) and three oplopane (6-8) sesquiterpenoids, a pair of benzopyran enantiomers (9 & 10) and a benzofuran derivative (11), along with six known sesquiterpenoid co-metabolites (12-17), have been obtained from the flower buds of Tussilago farfara. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. The absolute configurations of all the compounds except 11 were unequivocally assigned by various techniques, including Mosher's method and time-dependent density functional theory (TD-DFT) based calculations of 13C NMR and electronic circular dichroism (ECD) data. The C-8 absolute configuration on the sidechain of this group of bisabolane sesquiterpenoids was assigned for the first time. Our bioassays have established that compounds 3, 4, 13 and 14 showed significant α-glucosidase inhibitory activities, while 6, 8 and 14 displayed moderate antiproliferative effects against two human tumor cell lines A549 and MDA-MB-231. Further flow cytometric analysis revealed that 14 effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in A549 cells, in a dose-dependent manner.
Assuntos
Sesquiterpenos/química , Tussilago/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Flores/química , Flores/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , Estereoisomerismo , Tussilago/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismoRESUMO
Fourteen chromane derivatives of seven pairs of enantiomers (1-14) have been obtained from the ethanolic extract of the flower buds of Tussilago farfara L. Their structures with absolute configurations have been elucidated by detailed spectroscopic analyses, chemical methods, and particularly comparison of experimental ECD spectra with theoretically computed ones. Biological evaluations revealed that they did not show cytoprotective, antimicrobial, and α-glucosidase inhibitory activities.
Assuntos
Cromanos/química , Flores/química , Extratos Vegetais/química , Raízes de Plantas/química , Tussilago/química , Cromanos/isolamento & purificação , Teoria da Densidade Funcional , Humanos , Conformação Molecular , Extratos Vegetais/isolamento & purificação , Estereoisomerismo , Células Tumorais CultivadasRESUMO
Under the catalysis of chiral palladium(0)/ligand complex, the [4 + 2] cycloaddition between vinyl benzoxazinanones and barbiturate-based olefins proceeded readily and provided barbiturate-fused spirotetrahydroquinolines in up to 96% chemical yield with up to >99:1 dr and 97% ee. The absolute configuration of barbiturate-fused spirotetrahydroquinolines was clearly identified by X-ray single crystal structure analysis. The reaction mechanism was proposed to shed light on the enantioselective formation of barbiturate-fused spirotetrahydroquinolines.
RESUMO
Cyclin-dependent kinases 4/6 play an important role in regulation of cell cycle, and overexpress in a variety of cancers. Up to now, new CDK inhibitors still need to be developed due to its poor selectivity. Herein we report a novel series of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine anologues as potent CDK 4/6 inhibitors based on LY2835219 (Abemaciclib). Compound 10d, which exhibits approximate potency on CDK4/6 (IC50â¯=â¯7.4/0.9â¯nM), has both good pharmacokinetic characters and high selectivity on CDK1 compared with LY2835219. Overall, compound 10d could be a promising candidate and a good starting point as anticancer drugs.
Assuntos
Antineoplásicos/farmacologia , Quinases Ciclina-Dependentes/antagonistas & inibidores , Desenho de Fármacos , Imidazóis/farmacologia , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinases Ciclina-Dependentes/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imidazóis/síntese química , Imidazóis/química , Estrutura Molecular , Piperazinas/síntese química , Piperazinas/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Piridinas/síntese química , Piridinas/química , Pirimidinas/síntese química , Pirimidinas/química , Pirróis/síntese química , Pirróis/química , Relação Estrutura-AtividadeRESUMO
In this study, 19 octadecanoid derivatives-four pairs of enantiomers (1â»8), two racemic/scalemic mixtures (9â»10), and nine biosynthetically related analogues-were obtained from the ethanolic extract of a Chinese medicinal plant, Plantago depressa Willd. Their structures were elucidated on the basis of detailed spectroscopic analyses, with the absolute configurations of the new compounds assigned by time-dependent density functional theory (TD-DFT)-based electronic circular dichroism (ECD) calculations. Six of them (1, 3â»6, and 9) were reported for the first time, while 2, 7, and 8 have been previously described as derivatives and are currently obtained as natural products. Our bioassays have established that selective compounds show in vitro anti-inflammatory activity by inhibiting lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells.
Assuntos
Anti-Inflamatórios , Macrófagos/metabolismo , Óxido Nítrico/metabolismo , Plantago/química , Estearatos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/toxicidade , Macrófagos/patologia , Camundongos , Células RAW 264.7 , Estearatos/química , Estearatos/isolamento & purificação , Estearatos/farmacologiaRESUMO
Under catalysis of 10 mol % of Et3N, the [3 + 2] cycloaddition of barbiturate-based olefins with 3-isothiocyanato oxindoles underwent smoothly and afforded the desired dispirobarbiturates in up to 99% yield with up to 99:1 dr. The relative configuration of the dispirobarbiturates was unambiguously determined by X-ray single-crystal structure analysis. The reaction mechanism was proposed to shed light on the diastereoselective formation of the dispirobarbiturates.
RESUMO
Eleven undescribed glycosylated C21 steroids and nine known homologous glycosides with diverse acyl substituents, as well as their common steroid aglycone, have been obtained from the roots of Marsdenia tenacissima. Their structures were elucidated mainly by comprehensive spectroscopic analyses and comparison with previously reported analogues, with the absolute configuration assignment being supported by chemical degradation, X-ray crystallography and ECD exciton chirality method. Among them, two pairs of regioisomers were found to exist as inseparable equilibrium mixtures due to an interesting intramolecular transesterification, and nicotinoyl substitution was first reported for metabolites from the title plant. Screening of these compounds in a panel of bioassays revealed that two glycosides displayed mild inhibition against butyrylcholinesterase.
Assuntos
Marsdenia , Butirilcolinesterase , Esteroides/farmacologiaRESUMO
Twenty compounds comprising four pregnane steroids (2-4 & 20) and 16 pregnane glycosides (1 & 5-19) have been obtained from the ethanol extract of the roots of a Dai ethnological herb, Marsdenia tenacissima. Their structures were characterized on the basis of comprehensive spectroscopic analyses with 17 ones (1-17) being reported for the first time, including the rare cases (2 & 3) of free C21 steroids with 17α-acetyl substitution, compounds 4-7 bearing an unusual 14α-OH, and the first examples with simultaneous 14α-OH/17α-acetyl substitution (7) and glycosylation at C-12 position (10 & 11). An empirical rule for the identification of C-17 configuration, in C21 steroids incorporating the marsdenin constitution structure, was also proposed. All the isolates, along with an array of previously reported analogues in our compound library, were screened for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and six compounds exhibited moderate MDR reversal activity with reversal folds ranging from 1.92 to 4.44.
Assuntos
Marsdenia , Marsdenia/química , Estrutura Molecular , Esteroides/farmacologia , Esteroides/química , Pregnanos/farmacologia , Pregnanos/química , Glicosídeos/farmacologia , Glicosídeos/química , Resistência a Múltiplos MedicamentosRESUMO
Eighteen previously unreported pregnane glycosides, namely marsdenosides S1-S18, along with 15 known analogues, have been isolated from the stems of Marsdenia tenacissima. The structures of the undescribed compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation, X-ray crystallography and acid hydrolysis. All the isolates were evaluated for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and nine ones displayed moderate MDR reversal activity with reversal folds in the range of 2.45-9.01. The most active 12-O-acetyl-20-O-benzoyl-(14,17,18-orthoacetate)-dihydrosarcostin-3-O-ß-d-thevetopyranosyl-(1 â 4)-O-ß-d-oleandropyranosyl-(1 â 4)-O-ß-d-cymaropyranoside increased the sensitivity of MCF-7/ADR cell to adriamycin comparably to the reference drug verapamil (RF = 8.93).
Assuntos
Marsdenia , Marsdenia/química , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Pregnanos/farmacologia , Pregnanos/química , Resistência a Múltiplos MedicamentosRESUMO
Using iron(III)porphyrins in combination with (diacetoxyiodo)benzene allows for the conversion of 2,9-bis(bromomethyl)-4,7-diphenyl-1,10-phenanthroline into 4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid. This method provides a cost-effective and environmentally-friendly oxidation procedure using less toxic PhI(OAc)2 and biologically relevant iron(III)porphyrins. The catalytic activity of five kinds of iron-metallated functional porphyrins were investigated using different oxidants, including air, H2O2, PhI(OAc)2, PhIO and NaClO. Our results showed that the use of T(p-NO2)PPFeCl with PhI(OAc)2 as the oxidant in the presence of water displays remarkable activity for the desired oxidation reaction. The generality of this method was examined by synthesizing the carboxylic acids of pyridines and quinolines.
Assuntos
Benzeno/química , Compostos Férricos/química , Fenantrolinas/química , Porfirinas/química , Catálise , OxirreduçãoRESUMO
The electrochemical oxidation of catechols leads to the formation of o-benzoquinones. This property has been applied to effectively synthesize alpha-arylated products of alpha-oxoketene N,N-acetals with a tetrahydropyrimidine ring.
Assuntos
Acetais/química , Catecóis/química , Etilenos/química , Cetonas/química , Pirimidinas/química , Eletroquímica , Eletrodos , Elétrons , Oxirredução , Especificidade por SubstratoRESUMO
Six new compounds including four prenylated indole alkaloids (1-4) and two lignans (5-6), along with eight known cometabolites (7-14), were isolated from the flower buds of Tussilago farfara. Structures of the new compounds were elucidated by comparison with structurally related known analogues and also by comprehensive spectroscopic analyses. Their absolute configurations were determined by a variety of means including Mosher's method, Marfey's analysis, electronic circular dichroism (ECD) exciton chirality method and ECD calculations. Our bioassays have established that compounds 1 and 2 showed potent α-glucosidase inhibitory activity with IC50 values of 105 ± 4.7 and 35.2 ± 3.2 µM, respectively, while the known 13 and 14 exerted moderate DPPH radical scavenging activity with IC50 values of 45.2 ± 2.9 and 29.2 ± 2.0 µM, respectively.
Assuntos
Flores/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Alcaloides Indólicos/farmacologia , Lignanas/farmacologia , Tussilago/química , China , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Lignanas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Prenilação , Saccharomyces cerevisiae/enzimologia , alfa-GlucosidasesRESUMO
Four new octadecanoid derivatives (1-4) including a pair of enantiomers (1/2), along with 12 known analogues (5-16), were isolatedfrom the seeds of Ipomoea nil. Their structures were determined by detailed spectroscopic analyses and comparison with reported data of structurally related compounds, with the absolute configurations of 1 and 2 being assigned by an in situ dimolybdenum ECD method. Our bioassays revealed that these isolates did not show ABTS radical scavenging activity while 10 and 13 displayed better α-glucosidase inhibitory activity than the positive control acarbose (IC50 167.7 ± 1.55 µmol·L-1), with IC50 of 92.73 ± 3.12 and 11.39 ± 2.18µmol·L-1, respectively.
Assuntos
Ácidos Graxos/química , Inibidores de Glicosídeo Hidrolases/química , Ipomoea nil/química , Sementes/química , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/metabolismo , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/metabolismo , Concentração Inibidora 50 , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/metabolismoRESUMO
Seven new pentacyclic triterpenoids including six ursane-type, marinoids A-F (1-6), and one oleanane-type, marinoid G (7), along with five known analogues (8-12), were separated from the roots of Morinda officinalis var. officinalis. Their structures were assigned by spectroscopic means especially analysis of 2D NMR data, with the absolute configurations of 1 and 2 being determined via comparison of their experimental ECD spectra with the computed ones. Selective compounds displayed cytotoxic activity against two human osteosarcoma cell lines and also antibacterial effects against one Gram positive and one Gram negative strains.
Assuntos
Antibacterianos/farmacologia , Morinda/química , Triterpenos/farmacologia , Antibacterianos/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Triterpenos/isolamento & purificaçãoRESUMO
Two polyketides, stemonones A (1) and B (2) with new skeletons, were isolated from the roots of Stemona tuberosa. Their absolute structures were fully characterized by comprehensive spectroscopic analyses and comparison of experimental electronic circular dichroism (ECD) spectra with calculated ones. The plausible biosynthetic pathways for 1 and 2 were also proposed. Anti-inflammatory assay confirmed that the two compounds showed moderate inhibitory effects on ß-glucuronidase release in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factor.
Assuntos
Anti-Inflamatórios/química , Policetídeos/química , Stemonaceae/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Células Cultivadas , China , Glucuronidase/metabolismo , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Raízes de Plantas/química , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , RatosRESUMO
Under the catalysis of Pd2(dba)3 (2.5 mol%), PPh3 (10.0 mol%) and TMSCl (1.0 eq.), the formal [5+2] cycloaddition of vinylethylene carbonates to oxazol-5-(4H)-ones proceeded readily in THF at 60 °C to r.t., thus furnishing 3,4-dihydrooxepin-2(7H)-ones in 67-99% chemical yields. The chemical structure of one compound was confirmed by X-ray diffraction analysis, and the others were suggested by inference.
RESUMO
In the presence of TMSCl, the [3 + 2] cycloaddition of oxazol-5-(4H)-ones with nitrones proceeded smoothly and furnished the desired isoxazolidin-5-ones with high diastereoselectivities in reasonable chemical yields. The chemical structure of the title compounds was firmly confirmed by X-ray single-crystal structure analysis.