Triquinane Sesquiterpene Glycosides from the Basidiomycete Antrodiella zonata.

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.

A new dimeric (-)-5-methylmellein from cultures of the basidiomycete Inonotus sinensis.

(-)-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.

Nine New Pregnane Glycosides from the Cultivated Medicinal Plant Marsdenia tenacissima.

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.

Taccachatrones A-G, Highly Oxidized Steroids from the Rhizomes of Tacca chantrierii and Their Cytotoxicity Assessment.

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.

Structure and cytotoxicity of trichothecenes produced by the potato-associated fungus Trichothecium crotocinigenum.

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.

Two new sesquiterpenes from cultures of the fungus Irpex lacteus.

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].

Zopfiellasins A-D, Two Pairs of Epimeric Cytochalasins from Kiwi-Associated Fungus Zopfiella sp. and Their Antibacterial Assessment.

In our continuous search for antibacterial agents against Pseudomonas syringae pv. actinidiae (Psa) from kiwi-associated fungi, two pairs of epimeric cytochalasins, zopfiellasins A-D (1-4), were characterized from the fungus Zopfiella sp. The structures were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1 and 3 exhibited antibacterial activity against Psa with MIC values of 25 and 50 µg/mL, respectively. This is the first report of anti-Psa activity of cytochalasin derivatives.

Conosiligins A-D, Ring-Rearranged Tremulane Sesquiterpenoids from Conocybe siliginea.

Conosiligins A-D (1-4), four ring-rearranged sesquiterpenoids, were isolated from cultures of the basidiomycete Conocybe siliginea. Their structures and absolute configurations were determined by detailed spectroscopic analyses and equivalent circulating density (ECD) calculations. Compounds 1 and 2 possess a 5/8-fused ring system, while 3 has a 5/6-fused backbone conjugated with a γ-lactone. Compound 4 is a 5,6-seco tremulane derivative with the loss of a skeletal carbon, featuring a tetracyclic system involving a pyranone moiety. Compounds 3 and 4 inhibited Con A-induced T cell proliferation with IC50 values of 12.3 and 6.6 µM, respectively.

Psathyrins: Antibacterial Diterpenoids from Psathyrella candolleana.

Two skeletally novel tetracyclic diterpenoids, psathyrins A (1) and B (2), have been characterized from cultures of the basidiomycete Psathyrella candolleana. Their structures including absolute configurations were established by means of spectroscopic methods, as well as ECD calculations. They possess a novel 5/5/4/6-fuesd ring system, for which the biosynthetic pathway is proposed. Compounds 1 and 2 inhibited the growth of Staphylococcus aureus and Salmonella enterica.

Trichothecrotocins D-L, Antifungal Agents from a Potato-Associated Trichothecium crotocinigenum.

Seven new merosesquiterpenoids, trichothecrotocins D-J (1-7), two new trichothecene sesquiterpenoids, trichothecrotocins K (12) and L (13), and six known compounds (8-11, 14, and 15), were isolated from a potato-associated fungus, Trichothecium crotocinigenum. Compounds 5 and 6 were racemates which were further separated as pure enantiomers. Structures together with absolute configurations were established by extensive spectroscopic analysis, as well as quantum chemistry calculations on ECD and optical rotations. Compounds 1-4 are rare meroterpenoids featuring a seco-phenyl group, while 1 and 2 possessed a novel 6-6/5 fused ring system. Compounds 1-4, 8, 11, and 12 showed antifungal activity against four plant pathogens with MIC values of 8-128 µg/mL. It is suggested that the meroterpenoids produced by T. crotocinigenum may play an important role in the antifungal property of the fungus, thereby protecting the host plant, i.e., potato.

Sesquiterpenoids from Cultures of the Basidiomycetes Irpex lacteus.

Eight previously undescribed sesquiterpenoids, tremutins A-H (1-8), together with three known ones (9-11), were isolated from cultures of the basidiomycetes Irpex lacteus. Structures of the new compounds together with absolute configurations were elucidated on the basis of extensive spectroscopic methods, as well as single-crystal X-ray diffractions and equivalent circulating density calculations. Compounds 1 and 2 possess an unusual 6/7-fused ring system that might be derived from a tremulane framework. Compounds 3-7 and 9-11 are tremulane sesquiterpenoids of which 4 and 5 are the first tremulane examples with a 1,2-epoxy moiety to be reported. Compounds 6, 7, 10, and 11 possess weak activities to several human cancer cell lines. Compound 8 shows a weak inhibitory effect on NO production with a half maximal inhibitory concentration (IC50) value of 22.7 µM. Compound 1 inhibits the lipopolysaccharide (LPS)-induced proliferation of B lymphocyte cells with an IC50 value of 22.4 µM, while 2 inhibits concanavalin A (Con A)-induced T cell proliferation and LPS-induced B lymphocyte cell proliferation with IC50 values of 16.7 and 13.6 µM, respectively.

Immunosuppressive Nor-isopimarane Diterpenes from Cultures of the Fungicolous Fungus Xylaria longipes HFG1018.

Eighteen new nor-isopimarane diterpenes, xylarinorditerpenes A-R (1-18), along with two previously reported compounds, 14α,16-epoxy-18-norisopimar-7-en-4α-ol (19) and the labdane-type diterpene agatadiol (20), were isolated from cultures of the fungicolous fungus Xylaria longipes HFG1018 isolated from the wood-rotting basidiomycete Fomitopsis betulinus. The structure elucidation and relative configuration assignments of 1-18 were accomplished by interpretation of spectroscopic data and through computational methods. The absolute configurations of 1, 4, and 16 were determined by single-crystal X-ray diffraction. Compounds 1-16 possess an 18- or 19-nor-isopimarane skeleton, and compounds 17 and 18 possess an 18,19-dinor-isopimarane skeleton. Compounds 2-5, 9, 14, 19, and 20 showed immunosuppressive activity but were devoid of cytotoxicity against the cell proliferation by concanavalin A-induced T lymphocytes and lipopolysaccharide-induced B lymphocytes, with IC50 values varying from 1.0 to 27.2 µM and from 16.1 to 51.8 µM, respectively.

Two new compounds from cultures of the basidiomycete Daedaleopsis tricolor.

Two new compounds, daedatrin K (1) and 2-hydroxy-1-(5-(hydroxymethyl)furan-2-yl)propan-1-one (2), were isolated from cultures of the basidiomycetes Daedaleopsis tricolor. The new structures were elucidated on the basis of extensive spectroscopic methods. At the same time, two compounds were tested for their cytotoxicities against five human cancer cell lines. [Formula: see text].

Irpexolidal Represents a Class of Triterpenoid from the Fruiting Bodies of the Medicinal Fungus Irpex lacteus.

Irpexolidal (1), a triterpenoid with an unprecedented carbon skeleton, along with its biogenetic-related compound irpexolide A (2), were isolated from the fruiting bodies of the medicinal fungus Irpex lacteus. Irpexolidal features a 6/5/6/5/6/5-fused polycyclic skeletal system which arises from the eburicane-type triterpene by a 6,7- seco-6,8- cyclo pattern. The structures of 1 and 2 were established by means of extensive spectroscopic techniques, ECD calculation, and DP4+ probability based on GIAO NMR chemical shift calculations. The plausible biosynthetic pathways for compounds 1 and 2 were proposed. Their biological activities were evaluated.

Curtachalasins, immunosuppressive agents from the endophytic fungus Xylaria cf. curta.

Eleven new cytochalasins, curtachalasins F-P (1-11), were isolated from the rice fermentation of endophytic fungus Xylaria cf. curta. Their structures were identified by extensive spectroscopic methods, X-ray diffraction, and quantum chemistry calculations. Curtachalasin P possesses a unique 5/6/6/7 fused ring system. In the bioactivity screening for curtachalasins F-P, A-C, and E (1-15), compounds 1, 3-6, 8-13, and 15 did not show obvious cytotoxicity against primary mouse splenocytes. Furthermore, the immunosuppressive assay against concanavalin A (ConA) induced T lymphocyte cell proliferation and lipopolysaccharide (LPS) induced B lymphocyte cell proliferation showed that compound 1 results in significant selective inhibition on B-cell proliferation (IC50 value of 2.42 µM) and compound 10 has selective inhibition on T-cell proliferation (IC50 value of 12.15 µM). These interesting immunosuppressive properties of this class of compounds provide new clues to fulfill the urgent demand for new immunosuppressive drugs.

Synthesis of difluoromethylated 2-oxindoles and quinoline-2,4-diones via visible light-induced tandem radical cyclization of N-arylacrylamides.

Visible light-induced difluoromethylation of N-arylacrylamides to afford difluoromethylated 2-oxindoles and quinoline-2,4-diones with difluoromethyl 2-pyridyl sulfones as radical precursors has been disclosed. This method provides convenient access to a variety of 2-oxindoles and quinoline-2,4-diones under mild conditions via a proposed tandem radical addition/cyclization process along with good tolerance to various functional groups. In addition, preliminary experimental studies have revealed that water is a key factor in difluoromethylation and the reaction involves an oxidative quenching cycle of the photocatalyst.

Tricholopardins A and B, Anti-inflammatory Terpenoids from the Fruiting Bodies of Tricholoma pardinum.

Two new Tricholoma terpenoids, tricholopardins A and B, were isolated from the fruiting bodies of the basidiomycetes Tricholoma pardinum. Their structures were elucidated by spectroscopic methods, as well as electronic circular dichroism and optical rotatory dispersion calculations. Tricholopardin A potently inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophages with an IC50 of 0.08 µM. Its anti-inflammatory effects on three inflammatory mediators were also evaluated. A plausible biosynthetic pathway for these products is discussed.

Anti-inflammatory lupane triterpenoids from Menyanthes trifoliata.

A new lupane triterpenoid, 23-O-trans-feruloylcylicodiscic acid (1), as well as four known analogues (2‒5), was isolated from the EtOAc fraction of Menyanthes trefoliata. The structure of compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 2D NMR data. The structures of the known compounds were established by comparison of their spectroscopic data with that in the literature. Compounds 1, 2, and 4 exhibited certain anti-NO production activities.

Vibralactones U-W, three vibralactone derivatives from cultures of the basidiomycete Boreostereum vibrans.

Three new vibralactone derivatives, namely vibralactones U-W (1-3), together with vibralactone (4), have been isolated from cultures of the basidiomycete Boreostereum vibrans. Their structures were determined on the basis of spectroscopic methods and literature data. All compounds showed no activities to five human cancer cell lines.

Accessing benzooxadiazepines via formal [4 + 3] cycloadditions of aza-o-quinone methides with nitrones.

An unprecedented and efficient [4 + 3] cycloaddition of N-(ortho-chloromethyl)aryl amides with nitrones has been developed. This approach provides easy access to a series of seven-membered benzooxadiazepine derivatives in good to excellent yields (up to 99% yield) under mild reaction conditions.