RESUMEN
A cooperative Rh/achiral phosphoric acid-enabled [3+3] cycloaddition of in situ-generated carbonyl ylides with quinone monoimines has been developed. With the ability to build up the molecular complexity rapidly and efficiently, this method furnishes highly functionalized oxa-bridged benzofused dioxabicyclo[3.2.1]octane scaffolds bearing two quaternary centers in good to excellent yields under mild conditions. Moreover, the utility of the current method was demonstrated by gram-scale synthesis and elaboration of the products into various functionalized oxa-bridged heterocycles.
RESUMEN
Twenty-nine sesquiterpenoids, including pseudoguaiane-type (1-11), eudesmane-type (12-23), and carabrane-type (24-29), have been identified from the plant Carpesium abrotanoides. Of them, compounds 1-4, 12-15, and 24-27, namely carpabrotins A-L, are twelve previously undescribed ones. Compound 3 possessed a pseudoguaiane backbone with a rearrangement modification at C-11, C-12 and C-13, while compound 4 suffered a carbon bond break between the C-4 and C-5 to form a rare 4,5-seco-pseudoguaiane lactone. Compounds 1-3, 5, 13-16 and 25-27 exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 macrophages with IC50 values less than 40 µM, while compounds 1, 2, 5, 13, 14, 16, and 25-27 showed significant inhibitory activity comparable to that of dexamethasone. The anti-atopic dermatitis (AD) effects of compounds 5 and 16 were tested according to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in KM mice, and the results revealed that the major products 5 and 16 improved the histological features of AD-like skin lesions and mast cell infiltration in mice. This study suggested that sesquiterpenoids in C. abrotanoides should play a key role in its anti-inflammatory use.
Asunto(s)
Asteraceae , Óxido Nítrico , Sesquiterpenos , Animales , Ratones , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Asteraceae/química , Células RAW 264.7 , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Macrófagos/efectos de los fármacos , MasculinoRESUMEN
Two previously undescribed ergosterols containing a highly conjugated ring system, psathrosterols A and B (1 and 2), have been isolated from the fungus Psathyrella rogueiana. Their structures with absolute configurations were established by extensive spectroscopic methods, as well as single crystal X-ray diffraction. Compounds 1 and 2 showed inhibitory activity against NO production with IC50 values of 22.3 and 16.4 µM, respectively.
Asunto(s)
Agaricales , Estructura Molecular , Antiinflamatorios/farmacología , Cristalografía por Rayos X , Ergosterol/farmacologíaRESUMEN
In this study, two previously undescribed nitrogen-containing compounds, penisimplicins A (1) and B (2), were isolated from Penicillium simplicissimum JXCC5. The structures of 1 and 2 were elucidated on the basis of comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS data. The absolute configuration of 2 was determined by Marfey's method, ECD calculation, and DP4+ analysis. Both structures of 1 and 2 feature an unprecedented manner of amino acid-derivatives attaching to a polyketide moiety by C-C bond. The postulated biosynthetic pathways for 1 and 2 were discussed. Additionally, compound 1 exhibited significant acetylcholinesterase inhibitory activity, with IC50 values of 6.35 µM.
Asunto(s)
Alcaloides , Penicillium , Policétidos , Estructura Molecular , Policétidos/química , Acetilcolinesterasa/metabolismo , Penicillium/química , Péptidos/metabolismo , Alcaloides/químicaRESUMEN
Four undescribed cytochalasins (1-4) were isolated from the endophytic fungus Boeremia exigua. Structurally, boerelasin A (1) represents the first example of a cytochalasin with a rare 5/5 bicyclic carbon core. Boerelasin B (2) possesses an unprecedented 5/6/5/6/8 pentacyclic ring system. Boerelasin C (3), a derivative from the common biosynthetic intermediate to 1, is a macrocyclic ring-opening cytochalasin, and boerelasin D (4) contains an uncommon six-carbon alkyl acid side chain. The structures were elucidated based on spectroscopic methods, electronic circular dichroism, spin-spin coupling constants, and calculated nuclear magnetic resonance with DP4+ analysis. These compounds exhibited significant cytotoxicity against the tumor cells.
RESUMEN
In our ongoing study of fungal bioactive natural products, 12 previously undescribed triquinane sesquiterpene glycosides, namely, antrodizonatins A-L (1-12), and four known compounds (13-16) have been obtained from the fermentation of the basidiomycete Antrodiella zonata. The structures were established unambiguously via extensive spectroscopic analysis and theoretical calculations of electronic circular dichroism spectra. This is the first report of triquinane sesquiterpene glycosides. Compounds 1, 5, and 12 displayed antibacterial activity against Staphylococcus aureus with MIC50 values of 35, 34, and 69 µM, respectively.
Asunto(s)
Basidiomycota , Polyporales , Sesquiterpenos , Glicósidos/farmacología , Glicósidos/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Basidiomycota/química , Estructura MolecularRESUMEN
(-)-5-Methylmellein (1) and its new dimer (2) were isolated from cultures of the basidiomycete Inonotus sinensis. Their structures were elucidated on the basis of extensive spectroscopic methods including UV, IR, HR-EI-MS, 1D NMR and 2D NMR. The structure of Compound 2 was determined by single-crystal X-ray crystallographic analysis. Compound 2 was tested for the cytotoxicities against five human cancer cell lines.
Asunto(s)
Basidiomycota , Inonotus , Humanos , Estructura Molecular , Basidiomycota/química , Línea Celular TumoralRESUMEN
One new chamigrane sesquiterpene, antroalbol A (1), was isolated from the cultures of the higher fungus Antrodiella albocinnamomea. Its structure was established by means of spectroscopic methods, and the absolute configuration of 1 was confirmed by single crystal x-ray diffraction analysis. The compound was evaluated for its cytotoxicity against five human cancer cell lines, but no significant cytotoxicity was found.
Asunto(s)
Basidiomycota , Sesquiterpenos , Humanos , Estructura Molecular , Basidiomycota/química , Sesquiterpenos/químicaRESUMEN
Two unusual polyketide-sesquiterpene metabolites, craterodoratins T (1) and U (2), along with the known compound craterellin A (3), were isolated from the higher fungus Craterellus odoratus. The structures of isolated compounds were characterized based on nuclear magnetic resonance (NMR) and mass spectrum (MS) spectroscopic analysis, while the absolute configuration of the compounds was determined by theoretical NMR and electronic circular dichroism (ECD) calculations. Compound 1 possessed a rare structure with two aromatic groups. Compounds 1 and 3 showed immunosuppressive activity with IC50 values ranging from 5.516 to 19.953 µM.
Asunto(s)
Basidiomycota , Estructura Molecular , Basidiomycota/química , Hongos , Espectroscopía de Resonancia Magnética/métodos , Dicroismo Circular , InmunosupresoresRESUMEN
The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (1-9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the Rf values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC50 values of 37.5, 38.8, and 42.8 µM (L-NMMA was used as a positive control, IC50 39.3 µM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.
Asunto(s)
Marsdenia , Plantas Medicinales , Humanos , Plantas Medicinales/química , Marsdenia/química , China , Pregnanos/química , Glicósidos/químicaRESUMEN
The high efficiency and elegance of terpene synthases is fascinating in constructing the molecular skeleton of complicated terpenoids with multiple chiral centers. Although the rapid development of sequencing technology has led to the discovery of an increasing number of terpene synthases, the cyclization mechanisms of some terpene synthases remains elusive. Here, we report that a chimeric sesquiterpene synthase from Steccherinum ochraceum is responsible for the biosynthesis of (+)-hirsutene, a linear triquinane sesquiterpene. Structural validation, and isotope labeling experiments demonstrate that the biosynthesis of (+)-hirsutene employs an unusual cyclization mode, involving three different cyclization processes (C1-C11, C2-C9, C3-C6), one intramolecular 1,2-hydride shift (C9-C10) and three successive 1,2-alkyl shifts to construct the 5-5-5 fused ring skeleton of (+)-hirsutene.
Asunto(s)
Transferasas Alquil y Aril , Sesquiterpenos , Transferasas Alquil y Aril/genética , Catálisis , Sesquiterpenos Policíclicos , Polyporales , TerpenosRESUMEN
Herein, we report a novel strategy for the formation of copper carbene via the cycloisomerization of the π-alkyne-Cu(I) complex from terminal alkynes and tropylium tetrafluoroborate. Mechanistic studies and DFT calculations indicate that the reaction undergoes the intramolecular cycloisomerization process from the π-alkyne-Cu(I) complex to afford the copper carbene intermediate, followed by migratory insertion with the second terminal alkyne to afford the barbaralyl-substituted allenyl acid esters. In addition, we develop a mild and highly efficient Cu(I)-catalyzed cross-coupling protocol to synthesize 7-alkynyl cycloheptatrienes that has a broad functional group tolerance and is applicable to the late-stage functionalization of natural products.
RESUMEN
Antroxazole A (1), a chamigrane type sesquiterpene dimer containing an oxazole moiety, has been characterized from cultures of the fungus Antrodiella albocinnamomea. The structure with absolute configuration was determined by extensive spectroscopic methods and single crystal X-ray diffraction. A plausible biosynthetic pathway for 1 was proposed. Compound 1 exhibits inhibition specifically against the LPS-induced proliferation of B lymphocyte cells with an IC50 value of 16.3 µM.
Asunto(s)
Oxazoles , Sesquiterpenos , Hongos , Inmunosupresores/química , Lipopolisacáridos , Estructura Molecular , Oxazoles/farmacología , Polyporales , Sesquiterpenos/químicaRESUMEN
Continued interest in bioactive alkaloids led to the isolation of two undescribed alkaloids, ophiorrhines F (1) and G (2), from the aerial parts of Ophiorrhiza japonica. Their structures were elucidated based on spectroscopic methods, electronic circular dichroism, and calculated NMR with DP4+ analysis. These two alkaloids represent key biological genetic intermediates in the formation of ring C in the ophiorrhines. Compound 1 exhibited good inhibition on LPS-induced B cell proliferation with an IC50 value of 0.38 µM and showed significant selective inhibitory activity on a B cell proliferation response with a selective index of 548.42. A preliminary study indicated that 1 may have a new mechanism of immunosuppression.
Asunto(s)
Alcaloides , Rubiaceae , Alcaloides/química , Alcaloides/farmacología , Proliferación Celular , Inmunosupresores/farmacología , Estructura Molecular , Rubiaceae/químicaRESUMEN
Two previously undescribed monoterpenoid quinoline alkaloids, namely melotenucadines A and B, together with four known analogs, were characterized from the stems and leaves of Melodinus tenuicaudatus. The structures of the new compounds were established by extensive MS and NMR spectroscopic methods, while the absolute configuration was conducted by ECD calculations. Melotenucadine B was found to show certain cytotoxicity to MCF-7 cell (IC50 =27.3â µM).
Asunto(s)
Alcaloides , Apocynaceae , Quinolinas , Alcaloides/química , Apocynaceae/química , Alcaloides Indólicos/química , Estructura Molecular , Monoterpenos/análisis , Hojas de la Planta/química , Quinolinas/farmacologíaRESUMEN
Seven highly oxidized steroids, taccachatrones A-G (1-7), together with four known taccalonolides (8-11), were characterized from the rhizomes of Tacca chantrieri. The structures of 1-7 were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1-4 may be derived from taccalonolide derivatives by the degradation of three carbon atoms. Compounds 7, 8, 10, and 11 exhibited cytotoxicity to human cancer cell lines, indicating that the presence of a lactone moiety, as well as a double bond between C-22 and C-23, might play key roles in mediating their cytotoxicity.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Dioscoreaceae/química , Esteroides/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , China , Humanos , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Rizoma/química , Esteroides/aislamiento & purificaciónRESUMEN
Seven previously undescribed trichothecenes, named trichothecrotocins M-S (1-7), along with five known compounds, were isolated from rice cultures of the potato-associated fungus Trichothecium crotocinigenum. Their structures and absolute configurations were determined through spectroscopic methods, single-crystal X-ray diffraction, and quantum chemistry calculations on ECD. Compound 1 possesses a rare 6,11-epoxy moiety in the trichothecene family. Compound 6 exhibited strong cytotoxic activity against MCF-7 cancer cell lines with an IC50 value of 2.34 ± 0.45 µM. It promoted apoptosis induction in MCF-7 cells. Moreover, cell cycle analysis showed cell cycle arrest caused by compound 6 at the G2/M phase which resulted to cell proliferation inhibition and pro-apoptotic activity. Further quantitative real-time PCR (qRT-PCR) analysis confirmed that the G2/M arrest was accompanied by upregulation of p21 and down regulation of cyclins B1 in 6-treated MCF-7 cells.
Asunto(s)
Antineoplásicos/farmacología , Hypocreales/química , Solanum tuberosum/química , Tricotecenos/farmacología , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hypocreales/metabolismo , Células MCF-7 , Simulación del Acoplamiento Molecular , Estructura Molecular , Solanum tuberosum/metabolismo , Relación Estructura-Actividad , Tricotecenos/química , Tricotecenos/metabolismoRESUMEN
The biological activities of water-soluble components of edible mushroom Rubinoboletus ballouii (RB) were seldom reported. Polysaccharides of RB (RBP) were prepared and well-characterized using chemical analyses. The immunomodulatory properties of RBP were investigated using human monocyte-derived dendritic cells (moDC) in vitro, and cyclophosphamide (CTX)-induced immunosuppressive mouse model. Results showed that RBP was found to contain 80.6% (w/w) of neutral sugars including D-fucose, D-mannose, D-glucose and D-galactose (1.7:1.4:1.0:1.8), and 12.5% (w/w) of proteins, which composed of glutamine, threonine, serine, etc. RBP could promote the maturation of moDC and increase the secretion of IL-12p40, IL-10, and TNF-α. Furthermore, the stimulation of IL-12p40 production was inhibited by pretreatment with toll-like receptor (TLR)-4 blocker or NF-κB pathway blocker, suggesting that the activation of moDC by RBP was mediated through NF-κB pathway via TLR-4 receptor. On the other hand, in CTX-treated mice, RBP restored the loss of CD34bright CD45dim hematopoietic stem cells and increased IL-2 production in sera and splenocytes culture supernatant, as well as up-regulated the percentage of CD4+ T helper lymphocyte in mice splenocytes. These findings strongly suggested that RBP are the active ingredients of RB responsible for its immunostimulatory actions and deserved to be further investigated as cancer supplements.
Asunto(s)
Basidiomycota/química , FN-kappa B/metabolismo , Polisacáridos/uso terapéutico , Receptor Toll-Like 4/metabolismo , Animales , Humanos , Ratones , Polisacáridos/farmacologíaRESUMEN
A novel pH-activatable fluorescent probe, 1-(propan-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylic acid (L-1), based on ß-carboline derivatives, has been developed, which displays significant fluorescent response toward pH variation with high selectivity, good photo-stability and favorable pKa value. Moreover, L-1 can dynamically monitor the release of protons during ester hydrolysis reaction in consistent with enzymatic kinetics manner.
Asunto(s)
Carbolinas/química , Ésteres/metabolismo , Colorantes Fluorescentes/metabolismo , Carboxilesterasa/metabolismo , Ésteres/química , Colorantes Fluorescentes/química , Concentración de Iones de Hidrógeno , Hidrólisis , Indoles/química , Indoles/metabolismo , Cinética , Metales/químicaRESUMEN
Two new tremulane-type sesquiterpenes, irlactin L (1) and irlactin M (2) were isolated from cultures of the fungus Irpex lacteus, together with one known compound, 6-hydroxy-2,6-dimethyloct-7-enoic acid (3). Their structures were elucidated by spectroscopic data analysis. Compounds 1-2 were tested for their cytotoxicities against five human cancer cell lines and for their inhibitory activities against isozymes of 11ß-hydroxysteroid dehydrogenases (11ß-HSD).[Formula: see text].