ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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).
Subject(s)
Marsdenia , Marsdenia/chemistry , Molecular Structure , Glycosides/pharmacology , Glycosides/chemistry , Pregnanes/pharmacology , Pregnanes/chemistry , Drug Resistance, MultipleABSTRACT
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.
Subject(s)
Marsdenia , Marsdenia/chemistry , Molecular Structure , Steroids/pharmacology , Steroids/chemistry , Pregnanes/pharmacology , Pregnanes/chemistry , Glycosides/pharmacology , Glycosides/chemistry , Drug Resistance, MultipleABSTRACT
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.
Subject(s)
Marsdenia , Butyrylcholinesterase , Steroids/pharmacologyABSTRACT
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.
Subject(s)
Sesquiterpenes/chemistry , Tussilago/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Circular Dichroism , Flowers/chemistry , Flowers/metabolism , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/metabolism , Glycoside Hydrolase Inhibitors/pharmacology , Humans , Magnetic Resonance Spectroscopy , Molecular Conformation , S Phase Cell Cycle Checkpoints/drug effects , Sesquiterpenes/isolation & purification , Sesquiterpenes/metabolism , Sesquiterpenes/pharmacology , Stereoisomerism , Tussilago/metabolism , alpha-Glucosidases/chemistry , alpha-Glucosidases/metabolismABSTRACT
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.
Subject(s)
Flowers/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Indole Alkaloids/pharmacology , Lignans/pharmacology , Tussilago/chemistry , China , Free Radical Scavengers/isolation & purification , Free Radical Scavengers/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Indole Alkaloids/isolation & purification , Lignans/isolation & purification , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Prenylation , Saccharomyces cerevisiae/enzymology , alpha-GlucosidasesABSTRACT
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.
Subject(s)
Fatty Acids/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Ipomoea nil/chemistry , Seeds/chemistry , Fatty Acids/isolation & purification , Fatty Acids/metabolism , Glycoside Hydrolase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/metabolism , Inhibitory Concentration 50 , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/metabolismABSTRACT
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.
Subject(s)
Chromans/chemistry , Flowers/chemistry , Plant Extracts/chemistry , Plant Roots/chemistry , Tussilago/chemistry , Chromans/isolation & purification , Density Functional Theory , Humans , Molecular Conformation , Plant Extracts/isolation & purification , Stereoisomerism , Tumor Cells, CulturedABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Morinda/chemistry , Triterpenes/pharmacology , Anti-Bacterial Agents/isolation & purification , Cell Line, Tumor , China , Humans , Molecular Structure , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/isolation & purification , Oleanolic Acid/pharmacology , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Roots/chemistry , Triterpenes/isolation & purificationABSTRACT
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.
ABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents , Macrophages/metabolism , Nitric Oxide/metabolism , Plantago/chemistry , Stearates , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Lipopolysaccharides/toxicity , Macrophages/pathology , Mice , RAW 264.7 Cells , Stearates/chemistry , Stearates/isolation & purification , Stearates/pharmacologyABSTRACT
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.
ABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents/chemistry , Polyketides/chemistry , Stemonaceae/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Cells, Cultured , China , Glucuronidase/metabolism , Molecular Structure , Neutrophils/drug effects , Plant Roots/chemistry , Polyketides/isolation & purification , Polyketides/pharmacology , RatsABSTRACT
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.
Subject(s)
Antineoplastic Agents/pharmacology , Cyclin-Dependent Kinases/antagonists & inhibitors , Drug Design , Imidazoles/pharmacology , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyridines/pharmacology , Pyrimidines/pharmacology , Pyrroles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin-Dependent Kinases/metabolism , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Imidazoles/chemical synthesis , Imidazoles/chemistry , Molecular Structure , Piperazines/chemical synthesis , Piperazines/chemistry , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pyridines/chemical synthesis , Pyridines/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Pyrroles/chemical synthesis , Pyrroles/chemistry , Structure-Activity RelationshipABSTRACT
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.
ABSTRACT
In the presence of CuI, 1,3-dipolar cycloadditions of N,N'-cyclic azomethine imines with iminooxindoles proceeded readily and furnished novel oxindole spiro-N,N-bicyclic heterocycles in moderate to excellent chemical yields with excellent diastereoselectivities.
ABSTRACT
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.
ABSTRACT
Four tetramethyl 4,4'-(ethane-1,2-diylidene)bis[1-R-5-oxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylate] compounds, denoted class (1), are a series of conjugated buta-1,3-dienes substituted with a heterocyclic group. The compounds can be used as dyes and pigments due to their long-range conjugated systems. Four structures were studied using (1)H NMR, (13)C NMR and mass spectroscopy, viz. with R = 2,4,6-trimethylphenyl, (1a), R = cyclohexyl, (1b), R = tert-butyl, (1c), and R = isopropyl, (1d). A detailed discussion is presented regarding the characteristics of the three-dimensional structures based on NMR analysis and the X-ray crystal structure of (1a), namely tetramethyl 4,4'-(ethane-1,2-diylidene)bis[5-oxo-1-(2,4,6-trimethylphenyl)-4,5-dihydro-1H-pyrrole-2,3-dicarboxylate], C36H36N2O10. The conjugation plane and stability were also studied via quantum chemical calculations.