Enantioselective Total Syntheses of Manginoids†A and†C and Guignardones†A and†C.

An enantioselective synthetic approach for preparing manginoids and guignardones, two types of biogenetically related meroterpenoids, is reported. This bioinspired and divergent synthesis employs an oxidative 1,3-dicarbonyl radical-initiated cyclization and cyclodehydration of the common precursor to forge the central ring of the manginoids and guignardones, respectively, at a late stage. Key synthetic steps include silica-gel-promoted semipinacol rearrangement to form the 6-oxabicyclo[3.2.1]octane skeleton and the Suzuki-Miyaura reaction of vinyl bromide to achieve fragment coupling. This synthesis protocol enables the asymmetric syntheses of four fungal meroterpenoids from commercially available materials.

Terpenoids from the Chinese liverwort Odontoschisma grosseverrucosum and their antifungal virulence activity.

Eight undescribed terpenoids, namely, odongrossins A-H, together with two known terpenoids were isolated from Odontoschisma grosseverrucosum Stephani (Cephaloziaceae). Their structures were established based on NMR data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction measurements. Odongrossin A and odongrossin G displayed moderate anti-virulence activities against CDR1-and CDR2-efflux-pump-deficient Candida albicans DSY654. Further investigation of odongrossin A revealed that it inhibited adhesion and biofilm formation on C. albicans DSY654. The results regarding the transcription levels of genes demonstrated that odongrossin A could regulate the expression of genes that are associated with the virulence of C. albicans DSY654.

Terpenoids from the Chinese liverwort Heteroscyphus coalitus and their anti-virulence activity against Candida albicans.

In this study, 14 previously undescribed terpenoids were isolated from the Chinese liverwort Heteroscyphus coalitus (Hook.) Schiffner, including a rare harziane type diterpenoid, heteroscyphsic acid A; eight ent-clerodane diterpenoids, heteroscyphsic acids B-I; four labdane diterpenoids, heteroscyphins A-D; and one guaiane sesquiterpene, heteroscyphin E; as well as a known ent-junceic acid. Their structures were determined by a combination of MS, NMR spectroscopy, electronic circular dichroism (ECD) and single crystal X-ray diffraction analyses. The anti-virulence activity of the isolated compounds against Candida albicans DSY654 demonstrated that most of them could block hyphal growth at concentrations ranging from 4-32 µg/ml. Further investigation of the most active compound, heteroscyphin D, revealed that it could suppress the ability of C. albicans DSY654 to adhere to A549 cells and form biofilms, and modulate the transcription of related genes in this fungus.

Prenylated Bibenzyls from the Chinese Liverwort Radula constricta and Their Mitochondria-Derived Paraptotic Cytotoxic Activities.

Nine new prenylated bibenzyls, radstrictins A-I (1-9), and 11 known congeners were obtained from the Chinese liverwort Radula constricta. Their structures were identified by analysis of HRMS, NMR, and electronic circular dichroism data. Radstrictins A-F (1-6) were isolated as a racemate or scalemic mixtures. All the isolated compounds were subjected to cytotoxicity assessment. Methyl 2,4-dihydroxy-3-(3-methyl-2-butenyl)-6-phenethylbenzoate (10) exhibited significant activity against human lung cancer cell lines A549 and NCI-H1299 with IC50 values of 6.0 and 5.1 µM, respectively. Further research revealed that cell death triggered by 10 occurred via mitochondria-derived paraptosis.

Secondary metabolites from the endolichenic fungus Ophiosphaerella korrae.

The isolation of the cytotoxic fractions from the endolichenic fungus Ophiosphaerella korrae yielded six new metabolites, including five polyketides (ophiofuranones A (1) and B (2), with unusual furopyran-3,4-dione-fused heterocyclic skeletons, ophiochromanone (3), ophiolactone (4), and ophioisocoumarin (5)), one sesquiterpenoid ophiokorrin (10), and nine known compounds. Their structures were established on the basis of the analysis of HRESIMS and NMR spectroscopic data. ECD calculations, GIAO NMR shift calculations and single-crystal X-ray diffraction were employed for the stereo-structure determination. A plausible biogenetic pathway for the ophiofuranones A (1) and B (2) was proposed. The cytotoxic assay suggested that the five known perylenequinones mainly contributed to the cytoxicity of the extract. Further phytotoxic studies indicated that ophiokorrin inhibited root elongation in the germination of Arabidopsis thaliana with an IC50 value of 18.06 µg mL-1.

Plagiochianins A and B, Two ent-2,3- seco-Aromadendrane Derivatives from the Liverwort Plagiochila duthiana.

Two novel ent-aromadendrane derivatives, plagiochianin A (1), possessing an unprecedented 2,3:6,7-di- seco-6,8-cyclo-aromadendrane carbon scaffold conjugated with three cyclic acetals, and plagiochianin B (2), an exceptional pyridine type aromadendrane alkaloid, were isolated from the Chinese liverwort Plagiochila duthiana. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction and electronic circular dichroism calculations. A plausible biogenetic pathway of these two compounds is presented, and their acetylcholinesterase inhibitory activities are preliminarily tested using TLC-bioautographic assays.

Heptaketides from an Endolichenic Fungus Biatriospora sp. and Their Antifungal Activity.

Twelve new heptaketides, biatriosporins A-L (1-12), biatriosporin M (13) (a ramulosin derivative), and 19 known compounds (14-32) were isolated from the endolichenic fungus Biatriospora sp. (8331C). The structures of these compounds were determined by analyzing MS and NMR data. The absolute configurations of compounds 1, 2, 7, and 9 were determined by single-crystal X-ray diffraction analysis, whereas compound 10 was deduced with Mosher's method. Four of the compounds were active in an antifungal assay. The most potent compound, compound 4, also sensitized clinically derived azole-resistant Candida albicans strains to fluconazole (FLC). A mechanistic investigation revealed that 4 inhibited the function of efflux pumps and reduced the transcriptional expression of the efflux-pump-related genes CDR1 and CDR2.

Indoline Amide Glucosides from Portulaca oleracea: Isolation, Structure, and DPPH Radical Scavenging Activity.

A polyamide column chromatography method using an aqueous ammonia mobile phase was developed for large-scale accumulation of water-soluble indoline amide glucosides from a medicinal plant, Portulaca oleracea. Ten new [oleraceins H, I, K, L, N, O, P, Q, R, S (1-10)] and four known [oleraceins A-D (11-14)] indoline amide glucosides were further purified and structurally characterized by various chromatographic and spectroscopic methods. The DPPH radical scavenging activities of oleraceins K (5) and L (6), with EC50 values of 15.30 and 16.13 µM, respectively, were twice that of a natural antioxidant, vitamin C; the EC50 values of the 12 other indoline amides, which ranged from 29.05 to 43.52 µM, were similar to that of vitamin C. Structure-activity relationships indicated that the DPPH radical scavenging activities of these indoline amides correlate with the numbers and positions of the phenolic hydroxy groups.

Tetramic Acids and Pyridone Alkaloids from the Endolichenic Fungus Tolypocladium cylindrosporum.

Three new tetramic acid derivatives, tolypocladenols A1, A2, and B (1-3), a new pyridone alkaloid, tolypyridone A (4), and a new coumarin derivative, 3,8-dihydroxy-4-(4-hydroxyphenyl)-6-methylcoumarin (5), together with four known compounds (6-9) were isolated from the endolichenic fungus Tolypocladium cylindrosporum, which inhabits the lichen Lethariella zahlbruckneri. Structures of these compounds were determined by comprehensive analysis of spectroscopic data and single-crystal X-ray diffraction determination. Bioassay of the isolated compounds found that pyridoxatin (7) was cytotoxic to human cancer cells by induction of G0/G1 cell cycle arrest and apoptosis.

Identification and biological evaluation of secondary metabolites from the endolichenic fungus Aspergillus versicolor.

A chemical investigation of the endolichenic fungus Aspergillus versicolor (125a), which was found in the lichen Lobaria quercizans, resulted in the isolation of four novel diphenyl ethers, named diorcinols F-H (1-3, resp.) and 3-methoxyviolaceol-II (4), eight new bisabolane sesquiterpenoids, named (-)-(R)-cyclo-hydroxysydonic acid (5), (-)-(7S,8R)-8-hydroxysydowic acid (6), (-)-(7R,10S)-10-hydroxysydowic acid (7), (-)-(7R,10R)-iso-10-hydroxysydowic acid (8), (-)-12-acetoxy-1-deoxysydonic acid (9), (-)-12-acetoxysydonic acid (10), (-)-12-hydroxysydonic acid (11), and (-)-(R)-11-dehydrosydonic acid (12), two new tris(pyrogallol ethers), named sydowiols D (13) and E (14), and fifteen known compounds, 15-29. All of the structures were determined by spectroscopic analyses, and a number of them were further identified through chemical transformations and electronic circular dichroism (ECD) calculations. Preliminary bioassays of these isolates for the determination of their inhibitory activities against the fungus Candida albicans, and their cytotoxicities against the human cancer cell lines PC3, A549, A2780, MDA-MB-231, and HEPG2 were also evaluated.

Notolutesins A-J, dolabrane-type diterpenoids from the Chinese liverwort Notoscyphus lutescens.

Ten new dolabrane-type diterpenoids, notolutesins A-J (1-10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 µM against the PC3 human prostate cancer cell line.

Two new cadinane-type sesquiterpenes from the Chinese liverwort Frullania serrata.

Two new cadinane-type sesquiterpenes, frullanic acid (1) and frullanic acid methyl ester (2), together with four known bibenzyls, brittonin B (3), 3,3'-dimethoxy-4,5-methylenedioxybibenzyl (4), 3,4,5,3',4'-penlamethoxybibenzyl (5) and (±)-3-(4'-methoxybenzyl)-5,6-dimethoxyphtbalide (6), were isolated from the Chinese liverwort Frullania serrata. The structures of the new metabolites were elucidated by analysing the spectroscopic data (1D NMR, 2D NMR, HR-ESI-MS and IR). The absolute configurations of compounds 1 and 2 were determined by comparing the experimental and calculated electronic circular dichroism spectra predicted by using time-dependent density functional theory as well as the CD exciton chirality method.

Theoretical study of the adsorption of pentachlorophenol on the pristine and Fe-doped boron nitride nanotubes.

To explore the novel application of boron nitride nanotubes (BNNTs), we investigated the interaction of pentachlorophenol (PCP) pollutant with the pristine and Fe doped (Fe-doped) (8, 0) single-walled BNNTs by performing density functional theory calculations. Compared with the weak physisorption on the pristine BNNT, PCP molecule presents strong chemisorption on the Fe-doped BNNT. The calculated data for the electronic properties indicate that doping Fe atom into the BNNT significantly improves the electronic transport property of BNNT, induces magnetism in the BNNT, and increases its adsorption sensitivity toward PCP molecule. It is suggested that doping BNNTs with Fe is an available strategy for improving the properties of BNNTs, and that Fe-doped BNNT would be a potential resource for adsorbing PCP pollutant in environments.

Aphadilactones A-D, four diterpenoid dimers with DGAT inhibitory and antimalarial activities from a Meliaceae plant.

Aphadilactones A-D (1-4), four diastereoisomers possessing an unprecedented carbon skeleton, were isolated from the Meliaceae plant Aphanamixis grandifolia. Their challenging structures and absolute configurations were determined by a combination of spectroscopic data, chemical degradation, fragment synthesis, experimental CD spectra, and ECD calculations. Aphadilactone C (3) with the 5S,11S,5'S,11'S configuration showed potent and selective inhibition against the diacylglycerol O-acyltransferase-1 (DGAT-1) enzyme (IC50 = 0.46 ± 0.09 µM, selectivity index > 217) and is the strongest natural DGAT-1 inhibitor discovered to date. In addition, compounds 1-4 showed significant antimalarial activities with IC50 values of 190 ± 60, 1350 ± 150, 170 ± 10, and 120 ± 50 nM, respectively.

Peniciketals A-C, new spiroketals from saline soil derived Penicillium raistrichii.

Peniciketals A-C (1-3), three new spiroketals with a benzo-fused 2,8-dioxabicyclo[3.3.1]nonane moiety, were isolated from the saline soil derived fungus Penicillium raistrichii. Their structures including absolute configurations were established by NMR, X-ray diffraction, and ECD calculations. Their cytotoxicities were tested against A549, HL-60, and K562 cell lines, and 1-3 showed the selective effects on HL-60 cells with IC50 values of 3.2, 6.7, and 4.5 µM, respectively.

cis-clerodane diterpenes from the liverwort Scapania ciliata.

Chemical investigation of the Chinese liverwort Scapania ciliata led to the isolation of four new cis-clerodane lactones, named ciliatolides A-D (1-4, resp.), among which compound 1 was found to be a tetranorclerodanoid. Their structures were determined by extensive analysis of spectroscopic data, and, in the case of compound 1, together with a single-crystal X-ray diffraction analysis. The absolute configurations were established by analysis of the CD spectra and by quantum-chemical CD calculations. The cytotoxicities of compounds 1-4 were preliminarily tested against the PC3 and MCF-7 cell lines.

Highly oxygenated ent-pimarane-type diterpenoids from the Chinese liverwort Pedinophyllum interruptum and their allelopathic activities.

Ten highly oxygenated ent-pimarane-type diterpenoids, pedinophyllols A-J (1-10), were isolated from the Chinese liverwort Pedinophyllum interruptum. Their structures were determined by comprehensive analysis of spectroscopic data together with single-crystal X-ray diffraction analysis. The absolute configurations were elucidated by comparison of experimental and theoretically calculated electronic circular dichroism spectra. Allelopathic testing showed that several new diterpenoids inhibited germination of Arabidopsis thaliana seeds.

Secondary metabolites from the Chinese liverwort Cephaloziella kiaeri.

Sixteen new clerodane diterpenoids, cephaloziellins A-P (1-16), and two known analogues (17 and 18) were isolated from an EtOH extract of the Chinese liverwort Cephaloziella kiaeri. The structures of the new compounds were elucidated from extensive spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the structures of 5, 9, and 15 were confirmed by single-crystal X-ray diffraction analyses. The absolute configurations of all new compounds were established by comparing experimental and calculated electronic circular dichroism spectra.

Interconversion of the pallambins through photoinduced rearrangement.

A new photoinduced interconversion of four naturally occurring 19-nor-7,8-secolabdane diterpenoids was discovered and analyzed. The photochemical mechanism, intramolecular diradical rearrangement reaction, was investigated by time-lapse monitoring of the end product formations with HPLC and UV, as well as detailed theoretical calculations.

Serratustones A and B representing a new dimerization pattern of two types of sesquiterpenoids from Chloranthus serratus.

Serratustones A (1) and B (2), featuring a new carbon skeleton and representing a novel dimerization pattern of two different types of sesquiterpenoids, were isolated from Chloranthus serratus. Their structures with absolute configuration were determined on the basis of a detailed explanation of spectroscopic data, X-ray crystallography, and CD analysis in combination with ECD calculation.