Bioactive Pimarane Diterpenes from the Arctic Fungus Eutypella sp. D‐1

Two new pimarane diterpenes, libertellenone M ( 1 ) and libertellenone N ( 2 ), together with five known compounds were isolated from the culture extract of Eutypella sp. D‐1 derived from high‐latitude soil of the Arctic. The structures of these compounds were determined by spectroscopic data as well as experimental and calculated electronic circular dichroism (ECD) analysis. Antimicrobial and cytotoxic activities of the isolated compounds were evaluated. Compound 3 exhibited weak antibacterial activity against Escherichia coli, Bacillus subtilis, and Vibrio vulnificus, each with MIC values of 16 μg/mL. Compounds 2 and 3 showed moderate cytotoxic activity against K562 and MCF‐7 cell lines with IC₅₀ values of 7.67 and 9.57 μm , respectively.     

Bioactive 3,8‐Epoxy Iridoids from Valeriana jatamansi

Twelve 3,8‐epoxy iridoids, including four new compounds, jatamanins R–U ( 1 – 4 ), and eight known compounds ( 5 – 12 ), were obtained from the roots and rhizomes of Valeriana jatamansi. The structures were elucidated from analysis of spectroscopic data. The absolute configurations of 1 – 4 were determined by comparison of experimental and literature ECD spectra. Moreover, the compounds were evaluated for cytotoxic effects against glioma stem cells, inhibition of NO production, activity against influenza A virus and reversal of multidrug resistance of HepG2/ADR cells. Compounds 9 and 12 showed significant cytotoxic potency against GSC‐18# (IC₅₀=1.351 and 4.439 μg ml^?1, respectively) and GSC‐3# (IC₅₀=10.88 and 6.348 μg ml^?1, respectively) glioma stem cells, while compound 12 was also slightly less potent against GSC‐12# (IC₅₀=13.45 μg ml^?1) glioma stem cell growth. In addition, compounds 9 and 12 displayed obvious inhibition of NO production (IC₅₀=4.6 and 15.8 μm , respectively).     

Cis-diastereoselectivity in pictet-spengler reactions of L-tryptophan and electronic circular dichroism studies

The diastereoselective synthesis of optically active 1,3‐disubstituted tetrahydro‐β‐carbolines using polar protic Pictet–Spengler cyclization of (S)‐tryptophan methyl ester with five aldehydes RCHO (R═CH₃, C₂H₅, C₃H₇, C₄H₉, and C₆H₅) was studied. As an alternate route, the cyclization of (S)‐tryptophan with the same aldehydes and subsequent methylation of the resulting tetrahydro‐β‐carboline carboxylic acids were also performed for comparison. ¹³C NMR and electronic circular dichroism (ECD) studies and time‐dependent density functional theory ECD calculations data established the relative 1,3 cis/trans and the absolute configuration (1S,3S/ 1R,3S) of the synthesized compounds. The solid‐state and solution ECD study of the prepared compounds, supported by ECD calculation and X‐ray data, afforded a reliable ECD method for the configurational assignment of 1,3‐disubstituted tetrahydro‐β‐carbolines and revealed the stereochemical factors that determine the characteristic ECD data. Chirality 24:789–795, 2012. © 2012 Wiley Periodicals, Inc.     

Two New Abietane Diterpenoids from Selaginella moellendorffii Hieron.

Two new abietane diterpenoids, (3S,5R,10S)‐3‐hydroxy‐12‐O‐demethyl‐11‐deoxy‐19(4→3)‐abeo‐cryptojaponol, 12,19‐dihydroxyabieta‐8,11,13‐trien‐7‐one, were isolated from Selaginella moellendorffii Hieron., together with one known abietane diterpenoid and four known tetracyclic triterpenoids. Their structures were characterized by their 1D‐ and 2D‐NMR, ECD and mass spectral studies. All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non‐small‐cell lung carcinoma cell lines A549 and human breast adenocarcinoma cell lines MDA‐MB‐231 and MCF‐7) in vitro. Among them, three compounds displayed modest cytotoxic activities against the above three human cancer cell lines with IC₅₀ values ranging from 16.28 to 40.67 μM.     

Cuceolatins A–D: New Bioactive Diterpenoids from the Leaves of Cunninghamia lanceolata

Four new diterpenoids named cuceolatins A–D, including three labdane‐type ( 1 – 3 ) and one abietane‐type ( 4 ) as well as three known labdane analogs ( 5 – 7 ), were reported from the leaves of Cunninghamia lanceolata. Structural assignments for these compounds were conducted by analyses of spectroscopic data, and their absolute configurations were determined by time‐dependent density functional theory (TD‐DFT) based electronic circular dichroism (ECD) calculations. Among them, the abietane‐type diterpenoid (11‐hydroxy‐12‐methoxyabieta‐8,11,13‐trien‐3‐one ( 4 )) showed significant cytotoxicity against human MDA‐MB‐231, MCF‐7, and HeLa tumor cell lines with IC₅₀ measurements of 4.3, 2.8 and 4.5 μm , respectively, while the labdane‐type diterpenoids with a 4α‐carboxy group ( 1 – 3 and 5 ) exhibited moderate antibacterial activity towards Bacillus subtilis and Staphylococcus aureus with IC₅₀ values all below 25 μm .     

Diterpenes from the Roots of Oryza sativa L. and Their Inhibition Activity on NO Production in LPS‐Stimulated RAW264.7 Macrophages

Two new pimarane diterpenoids, momilactone D ( 3 ) and momilactone E ( 5 ), along with three known diterpenoids, momilactone A ( 1 ), sandaracopimaradien‐3‐one ( 2 ), and oryzalexin A ( 4 ) were isolated from Oryza sativa roots. The chemical structures of the compounds were determined by spectroscopic data analysis. The isolated diterpenoids were evaluated for their ability to inhibit NO production and iNOS mRNA and protein expression in LPS‐stimulated RAW264.7 macrophages. Compound 4 showed strong inhibition activity on NO production, and compounds 1 and 4 decreased the expression of iNOS mRNA and protein levels.     

Neuroprotective Activities of Constituents from Phyllosticta capitalensis,an Endophyte Fungus of Loropetalum chinense var. rubrum

One new dioxolanone derivative, guignardianone G ( 1 ) and twelve known compounds ( 2 – 13 ) were isolated from the 95 % ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Among these known compounds, isoaltenuene ( 3 ), brassicasterol ( 7 ), 5,6-epoxyergosterol ( 8 ), citreoanthrasteroid A ( 9 ), demethylincisterol A ( 10 ), and chaxine C ( 11 ) were reported from Phyllosticta sp. for the first time. The structure of 1 was elucidated by 1D- and 2D-NMR experiments and HR-ESI-MS data analysis, and its absolute configuration was established through the comprehensive use of the methods of modified Mosher methods, calculations of ECD spectra and optical rotation values. The neuroprotective activity of compounds ( 1 – 9 , 11 – 13 ) were evaluated on PC12 cells damage induced by glutamate, and compounds 9 and 12 showed potential neuroprotective activities with half effective concentration (EC₅₀) of 24.2 and 33.9 μM, respectively.     

Highly Oxygenated Labdane Diterpenoids from Stevia rebaudiana and Their Anti-Atherosclerosis Activities

Five unknown labdane diterpenoids Stevelins A–E ( 1–5 ), three known labdane diterpenoids ( 6–8 ) and three labdane norditerpenoids ( 9–11 ) were isolated from the Stevia rebaudiana. The structures were determined primarily via NMR spectroscopic data and HR-ESI-MS experiments. X-ray crystallography using CuK_α radiation was used to determine the absolute configurations of 1 , and the absolute configurations of 2–5 were deduced by electronic circular dichroism (ECD) calculations. The potential anti-atherosclerosis activities of all compounds were evaluated by measuring their inhibitory effects on the macrophage foam cell formation. As a result, most isolated compounds could significantly inhibit oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment for atherosclerosis.     

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

A new phloroglucinol derivative, named eucalyptin B ( 1 ), along with five related known compounds ( 2 – 6 ), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D‐ and 2D‐NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds ( 1 – 6 ) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B ( 1 ) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B ( 1 ), the apoptosis factor proteins (Bcl2 and Bax) and caspase‐3 levels in A549 cells were also determined by Western‐blot analysis. By cytotoxic assay, eucalyptin B ( 1 ) exhibited potent cytotoxicity against A549 cells with an IC₅₀ value of 1.51 μm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B ( 1 ) inhibited 5‐fold and increased 10‐folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11‐fold increase in the level of caspase‐3 confirmed eucalyptin B ( 1 ) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B ( 1 ) has promising cytotoxic activity in tumor cells, especially in A549.     

A Novel Sulfated Holostane Glycoside from Sea Cucumber Holothuria leucospilota

A new sulfated holostane glycoside, leucospilotaside B ( 1 ), together with the two related structurally known compounds holothurin B₂ ( 2 ) and holothurin B ( 3 ), was isolated from sea cucumber Holothuria leucospilota collected from the South China Sea. The structure of 1 was elucidated by spectral analysis (¹H‐, ¹³C‐, and 2D‐NMR, ESI‐MS, and HR‐ESI‐MS) and chemical methods. The compounds 1 – 3 possess the same disaccharide moiety, but were different in the side chains of the triterpene aglycone. Compound 1 showed significant cytotoxicities against four human tumor cell lines, HL‐60, MOLT‐4, A‐549, and BEL‐7402.     

Chiroptical study of cryptophanes subjected to self‐encapsulation

In 1,1,2,2‐tetrachloroethane‐d₂, the ¹²⁹Xe NMR spectrum of the Xe@cryptophane‐223 complex bearing seven acetate groups (Xe@ 1 complex) shows an unusually broad signal compared with that of its congeners (Chapellet, LL. et al. J. Org. Chem. 2015 ;80:6143–6151). To interpret this unexpected behaviour, a ¹H NMR analysis and a thorough study of the chiroptical properties of 1 as a function of the nature of the solvent have been performed. The ¹H NMR spectra of 1 reveal that a self‐encapsulation phenomenon takes place in DMSO‐d₆ and 1,1,2,2‐tetrachloroethane‐d₂ solvents. Thanks to the separation of the two enantiomers of 1 by HPLC on chiral stationary phase, the two enantiomers of 1 have been studied in detail by polarimetry, electronic (ECD), and vibrational (VCD) circular dichroism spectroscopies. Except for ECD spectroscopy, these chiroptical techniques reveal spectroscopic changes as a function of the nature of the solvent. For instance, in DMSO and 1,1,2,2‐tetrachloroethane, in which the self‐encapsulation phenomenon takes place, the sign of the specific optical rotation of [CD(?)₂₅₄]‐ 1 and [CD(+)₂₅₄]‐ 1 is changed. These results have then been compared with those obtained with cryptophane‐223 bearing only one acetate group on the propylenedioxy linker (compound 2 ) and with cryptophane‐223 bearing six acetate groups (compound 3 ). A self‐encapsulation phenomenon is also observed with compound 2 . Finally, compounds 2 and 3 show different chiroptical properties compared with those obtained with the two enantiomers of compound 1 .     

Trichodermaloids A–C,Cadinane Sesquiterpenes from a Marine Sponge Symbiotic Trichoderma sp. SM16 Fungus

Three new cadinane sesquiterpenes, trichodermaloids A ( 1 ), B ( 2 ), and C ( 5 ) were isolated from a symbiotic fungus Trichoderma sp. SM16 derived from the marine sponge Dysidea sp., together with three known ones, aspergilloid G ( 3 ), rhinomilisin E ( 4 ), and rhinomilisin G ( 6 ). The complete structures of three new compounds were determined by HR‐MS and NMR spectroscopic analyses coupled with ECD calculations. The absolute configurations of two known compounds ( 4 and 6 ) were determined for the first time. The six isolates were inactive as antibacterial agents. However, trichodermaloids A and B have shown cytotoxicity on human NCIH‐460 lung, NCIC‐H929 myeloma, and SW620 colorectal cancer cell lines with IC₅₀ values at the range of 6.8–12.7 μm .     

Synthesis,Structural Characterization,and Chiroptical Studies of Bidentate Salen‐Type Lanthanide (III) Complexes

The salen‐type ligand prepared with (R,R) diphenylethan‐1,2‐diamine and salicylaldehyde provides stable and inert complexes KLnL₂ upon simple reaction with lanthanide halides or pseudohalides LnX₃ (Ln = Tb³⁺‐Lu³⁺; X = Cl^? or TfO^?) of its potassium salt. All the complexes were completely characterized through nuclear magnetic resonance (NMR), electronic circular dichroism (ECD) in the UV and some (Er³⁺, Tm³⁺, Yb³⁺) also with Near‐IR ECD (NIR‐ECD) and luminescence (Tb³⁺, Tm³⁺). Careful analysis of the NMR shifts demonstrated that the complexes are isostructural in solution and afforded an accurate geometry. This was further confirmed by means of Density Functional Theory (DFT) optimization of the Lu³⁺ complex, and by comparing the ligand‐centered experimental and time‐dependent TD‐DFT computed UV‐ECD spectra. As final validation, we used the NIR‐ECD spectrum of the Yb³⁺ derivative calculated by means of Richardson's equations. The excellent match between calculated and experimental ECD spectra confirm the quality of the NMR structure.  Chirality 27:857–863, 2015. © 2015 Wiley Periodicals, Inc.     

Three New Indole Diketopiperazine Alkaloids from Aspergillus ochraceus

Asperochramides A – D ( 1  –  4 ), a new natural product and three new indole diketopiperazine alkaloids, along with seven known analogs ( 5  –  11 ), were isolated from the ethyl acetate extract of Aspergillus ochraceus. Their structures were elucidated by extensive spectroscopic analyses, ECD calculation, and single‐crystal X‐ray diffraction analysis. Compounds 3 and 4 represent a rare group of indole diketopiperazine alkaloid with a 3‐hydroxyl‐2‐indolone moiety. The in vitro anti‐inflammatory effects of compounds 1 and 3  –  11 were investigated by using LPS‐stimulated murine macrophage RAW 264.7 cells. Compounds 1 , 8 , 10 , and 11 showed potential anti‐inflammatory activities.     

Pyriculins A and B,two monosubstituted hex‐4‐ene‐2,3‐diols and other phytotoxic metabolites produced by Pyricularia grisea isolated from buffelgrass (Cenchrus ciliaris)

Pyricularia grisea has been identified as a foliar pathogen on buffelgrass (Cenchrus ciliaris ) in North America and was studied as a potential source of phytotoxins for buffelgrass control. Two monosubstituted hex‐4‐ene‐2,3‐diols, named pyriculins A and B, were isolated from its culture filtrate organic extract together with (10S ,11S )‐(−)‐epipyriculol, trans ‐3,4‐dihydro‐3,4,8‐trihydroxy‐1(2H )‐napthalenone, and (4S )‐(+)‐isosclerone. Pyriculins A and B were characterized by spectroscopic (essentially nuclear magnetic resonance [NMR], High‐resolution electrospray ionization mass spectrometry [HRESIMS]) and chemical methods such as (4E )‐1‐(4‐hydroxy‐1,3‐dihydroisobenzofuran‐1‐yl)hex‐4‐ene‐2,3‐diols. The relative and absolute configuration of these compounds was determined by a combination of spectroscopic (NMR, electronic circular dichroism [ECD]) and computational tools. When bioassayed in a buffelgrass coleoptile and radicle elongation test, (10S ,11S )‐(−)‐epipyriculol proved to be the most toxic compound. Seed germination was much reduced and slowed with respect to the control and radicles failed to elongate. All five compounds delayed germination, but only (10S ,11S )‐(−)‐epipyriculol was able to prevent radicle development of buffelgrass seedlings. It had no effect on coleoptile elongation, while the other four compounds caused significantly increased coleoptile development relative to the control.     

Vibrational and chiroptical spectroscopic characterization of γ‐turn model cyclic tetrapeptides containing two β‐Ala residues

The optical spectroscopic characterization of γ‐turns in solution is uncertain and their distinction from β‐turns is often difficult. This work reports systematic ECD and vibrational circular dichroism (VCD) spectroscopic studies on γ‐turn model cyclic tetrapeptides cyclo(Ala‐β‐Ala‐Pro‐β‐Ala) ( 1 ), cyclo(Pro‐β‐Ala‐Pro‐β‐Ala) ( 2 ) and cyclo(Ala‐β‐Ala‐Ala‐β‐Ala) ( 3 ). Conformational analysis performed at the 6‐31G(d)/B3LYP level of theory using an adequate PCM solvent model predicted one predominant conformer for 1‐3 , featuring two inverse γ‐turns. The ECD spectra in ACN of 1 and 2 are characterized by a negative n→π* band near 230 nm and a positive π→π* band below 200 nm with a long wavelength shoulder. The ECD spectra in TFE of 1‐3 show similar spectra with blue‐shifted bands. The VCD spectra in ACN‐d₃ of 1 and 2 show a +/?/+/? amide I sign pattern resulting from four uncoupled vibrations in the case of 1 and a sequence of two positive couplets in the case of 2 . A ?/+/+/? amide I VCD pattern was measured for 3 in TFE‐d₂. All three peptides give a positive couplet or couplet‐like feature (+/?) in the amide II region. VCD spectroscopy, in agreement with theoretical calculations revealed that low frequency amide I vibrations (at ～1630 cm^?1 or below) are indicative of a C₇ H‐bonded inverse γ‐turns with Pro in position 2, while γ‐turns encompassing Ala absorb at higher frequency (above 1645 cm^?1). Chirality, 2010. © 2010 Wiley‐Liss, Inc.     

Insecticidal Metabolites from the Rhizomes of Veratrum album against Adults of Colorado Potato Beetle,Leptinotarsa decemlineata

The dried rhizomes of Veratrum album were individually extracted with CHCl₃, acetone, and NH₄OH/benzene to test the toxic effects against the Colorado potato beetle, Leptinotarsa decemlineata, which is an important agricultural pest. Fifteen compounds in various amounts were isolated from the extracts using column and thin‐layer chromatography. The chemical structures of 14 compounds were characterized as octacosan‐1‐ol ( 1 ), β‐sitosterol ( 2 ), stearic acid ( 3 ), diosgenin ( 4 ), resveratrol ( 5 ), wittifuran X ( 6 ), oxyresveratrol ( 7 ), β‐sitosterol 3‐O‐β‐D ‐glucopyranoside ( 8 ), diosgenin 3‐O‐α‐L ‐rhamnopyranosyl‐(1→2)‐β‐D ‐glucopyronoside ( 9 ), oxyresveratrol 3‐O‐β‐D ‐glucopyranoside ( 10 ), jervine ( 11 ), pseudojervine ( 13 ), 5,6‐dihydro‐1‐hydroxyjervine ( 14 ), and saccharose ( 15 ) using UV, IR, MS, ¹H‐ and ¹³C‐NMR, and 2D‐NMR spectroscopic methods. However, the chemical structure of 12 , an oligosaccharide, has not fully been elucidated. Compounds 4, 6, 9 , and 10 were isolated from V. album rhizomes for the first time in the current study. The toxic effects of three extracts (acetone, CHCl₃, and NH₄OH/benzene) and six metabolites, 2, 2 + 4, 5, 7, 8 , and 11 , were evaluated against the Colorado potato beetle. The assay revealed that all three extracts, and compounds 7, 8 , and 11 exhibited potent toxic effects against this pest. This is the first report on the evaluation of the toxic effects of the extracts and secondary metabolites of V. album rhizomes against L. decemlineata. Based on these results, it can be concluded that the extracts can be used as natural insecticides.     

Bioactive Brominated Metabolites from the Natural Habitat and Tank‐Maintained Cuttings of the Jamaican Sponge Aplysina fistularis

Cut specimens of the common reef sponge of the Verongid family, Aplysina fistularis, were retained in flow‐through seawater tanks over a six‐week period to assess the metabolite profile of the sponge when subjected to stress, compare the profile with the source material, and assess the preliminary feasibility of the protocol for sponge culture. The living specimens were harvested, extracted with MeOH/CH₂Cl₂ 1 : 1, and subjected to column chromatography to identify metabolites. The brominated isoxazoline compounds, aerothionin ( 1 ) and 11‐oxoaerothionin ( 2 ), along with aeroplysinin 2 ( 3 ) and 2‐(3,5‐dibromo‐4‐hydroxyphenol)acetamide ( 4 ), were detected in the cuttings from the tank‐maintained sponge. An examination of the metabolite profile of the sponge from the natural habitat showed that the compounds 1 and 2 were present. The identities of all the compounds were ascertained by analysis of the mass‐spectral data and NMR spectra (¹H, ¹³C, HMBC, and HSQC) of the compounds, which were compared with reported data. The survival rate was 44% with limited necrosis or exposed skeletal tissue being observed in eight of the 18 cuttings, suggesting that protocol modifications would be required for culturing the sponge.     

New Cytotoxic Bibenzyl and Other Constituents from Bauhinia ungulata L. (Fabaceae)

A new bibenzyl, 2′‐hydroxy‐3,5‐dimethoxy‐4‐methylbibenzyl ( 1 ) and four known compounds identified as 2′‐hydroxy‐3,5‐dimethoxybibenzyl ( 2 ), liquiritigenin ( 3 ), guibourtinidol ( 4 ) and fisetinidol ( 5 ) were isolated from the roots of Bauhinia ungulata L. Phytochemical investigations of the stems of B. ungulata led to the isolation of the known compounds identified as liquiritigenin ( 3 ), guibourtinidol ( 4 ), fisetinidol ( 5 ), taraxerol ( 6 ), betulinic acid ( 7 ), taraxerone ( 8 ), glutinol ( 9 ), a mixture of sitosterol ( 10 ) and stigmasterol ( 11 ), pacharin ( 12 ), naringenin ( 13 ) and eriodictyol ( 14 ). The structures of these compounds were elucidated on the basis of their spectral data (IR, MS, 1D‐ and 2D‐NMR). The cytotoxicity of the bibenzyl 1 has been evaluated against four human cancer cell lines, showing the IC₅₀ values of 4.3 and 6.5 μg ml^?1 against pro‐myelocytic leukemia (HL‐60) and cervical adenocarcinoma (HEP‐2) cell lines, respectively. This article also registers for the first time the ¹³C‐NMR data of the known bibenzyl 2 .     

Two New Eudesmane-Type Sesquiterpene from Clonostachys sp. Y6-1and Their Cytotoxic Activity

Two undescribed eudesmane-type sesquiterpenoids together with four known compounds were isolated from Clonostachys sp. Y6-1 associated. Their chemical structures were unambiguously determined by NMR, mass spectrometry, and ¹³C-NMR calculation as well as DP4+ probability analyses. The absolute configurations of compounds 1 and 2 were determined by ECD calculation and X-ray single-crystal diffraction methods. Furthermore, all isolates were evaluated for in vitro cytotoxic activities against MCF-7, HCT-116, MDA-MB-231, and SW620 cancer cells. Among them, bioactivity evaluation of compound 5 revealed that weak activity (IC₅₀=66.55±0.82 μM) against SW620.