Itaconic acid derivatives and diketopiperazine from the marine-derived fungus Aspergillus aculeatus CRI322-03

Three metabolites, pre-aurantiamine (1), (−)-9-hydroxyhexylitaconic acid (4) and (−)-9-hydroxyhexylitaconic acid-4-methyl ester (5), together with two known compounds, paraherquamide E (6) and secalonic acid D (7), were isolated from the marine-derived fungus, Aspergillus aculeatus.     

Syntheses and characterization of titanium malonato and amino acid complexes: [Ti(cp)2(OOCCH2NMe2)] - The first structurally characterized α-amino acid titanium(III) complex

The reaction of [Ti(cp^∗)₂(BTMSA)] (1) (cp^∗ = η⁵-C₅Me₅, BTMSA = bis(trimethylsilyl)acetylene) with malonic acids ((HOOC)₂CR₂, R = H, Me) and N,N-dimethylglycine resulted in the formation of titanium(IV) dicarboxylato complexes [Ti(cp^∗)₂{(OOC)₂CR₂}] (R = H, 2; R = Me, 3) and an α-amino acid titanium(III) complex [Ti(cp^∗)₂(OOCCH₂NMe₂)] (4). The identities of complexes 2-4 were confirmed by microanalysis, ¹H and ¹³C NMR spectroscopy (2, 3), ESI-MS and CID experiments (2, 3) as well as by ESR and magnetic measurements (μ_eff = 1.81, 298 K) for 4. Single X-ray diffraction analyses of 2 and 4 exhibited monomolecular complexes in which the titanium atom is distorted tetrahedrally coordinated by two η⁵-C₅Me₅ rings and by the chelating bound malonato-κ²O,O′ (2) and N,N-dimethylglycinato-κ²O,O′ ligand (4).     

Synthesis, structures and ligating properties of 2,6-bis(phosphino)thiophenol derivatives

New t-butyl-aryl thioethers where the aryl group is 2,6-bis(phosphino)phenyl have been synthesized. The syntheses were completed via sequential ortho-lithiations of t-butylphenylsulfide, followed by chlorophosphine (ClPR₂) quenches; symmetric (2,6-bis(diphenylphosphino)phenyl, (4a)) and unsymmetric (2-diisopropylphosphino-6-diphenylphosphino)phenyl, (4b) aryl groups were obtained. Treatment of 4a with Li or Na naphthalenide yielded 2,6-bis(diphenylphosphino)thiophenol 5. Reactions of 4a or 5 with NiCl₂ · 6H₂O yielded nickel bis(phosphinothiophenolate) 6. Compounds 4a,b, 5 and 6 were characterized by ¹H and ³¹P NMR, and by mass-spectrometry. In addition, 4a, 5 and 6 were characterized by single crystal X-ray diffraction methods.     

Phenolic compounds with NF-κB inhibitory effects from the fungus Phellinus baumii

Chemical investigation of the fungus Phellinus baumii has resulted in characterization of five previously undescribed hispidin derivatives, phellibaumins A-E (1-5), as well as two pairs of new non-equivalent epimeric benzyl dihydroflavones, methylphelligrin A (9), epi-methylphelligrin A (10), methylphelligrin B (11), and epi-methylphelligrin B (12), together with five known compounds, interfungin B (6), phelligridin H (7), phelligridimer A (8), phelligrin A (13), and epi-phelligrin A (14). Phellibaumin A (1) was a novel hispidin derivative with a unique 3,4-dihydroxybenzofuran unit. These compounds exhibited NF-κB inhibitory activity with IC₅₀ values of 52.96 μM (1), 41.40 μM (2), 52.92 μM (5), 36.44 μM (9 and 10), and 22.46 μM (11 and 12), respectively.     

Tetra-acylated cyanidin 3-sophoroside-5-glucosides from the flowers of Iberis umbellata L. (Cruciferae)

The structures of 11 acylated cyanidin 3-sophoroside-5-glucosides (pigments 1-11), isolated from the flowers of Iberis umbellata cultivars (Cruciferae), were elucidated by chemical and spectroscopic methods. Pigments 1-11 were acylated with malonic acid, p-coumaric acid, ferulic acid, sinapic acid and/or glucosylhydroxycinnamic acids.Pigments 1-11 were classified into four groups by the substitution patterns of the linear acylated residues at the 3-position of the cyanidin. In the first group, pigments 1-3 were determined to be cyanidin 3-O-[2-O-(2-O-(acyl)-β-glucopyranosyl)-6-O-(trans-p-coumaroyl)-β-glucopyranoside]-5-O-[6-O-(malonyl)-β-glucopyranoside], in which the acyl moiety varied with none for pigment 1, ferulic acid for pigment 2 and sinapic acid for pigment 3. In the second one, pigments 4-6 were cyanidin 3-O-[2-O-(2-O-(acyl)-β-glucopyranosyl)-6-O-(4-O-(β-glucopyranosyl)-trans-p-coumaroyl)-β-glucopyranoside]-5-O-[6-O-(malonyl)-β-glucopyranoside], in which the acyl moiety varied with none for pigment 4, ferulic acid for pigment 5 and sinapic acid for pigment 6. In the third one, pigments 7-9 were cyanidin 3-O-[2-O-(2-O-(acyl)-β-glucopyranosyl)-6-O-(4-O-(6-O-(trans-feruloyl)-β-glucopyranosyl)-trans-p-coumaroyl)-β-glucopyranoside]-5-O-[6-O-(malonyl)-β-glucopyranoside], in which the acyl moiety varied with none for pigment 7, ferulic acid for pigment 8, and sinapic acid for pigment 9. In the last one, pigments 10 and 11 were cyanidin 3-O-[2-O-(2-O-(acyl)-β-glucopyranosyl)-6-O-(4-O-(6-O-(4-O-(β-glucopyranosyl)-trans-feruloyl)-β-glucopyranosyl)-trans-p-coumaroyl)-β-glucopyranoside]-5-O-[6-O-(malonyl)-β-glucopyranoside], in which acyl moieties were none for pigment 10 and ferulic acid for pigment 11.The distribution of these pigments was examined in the flowers of four cultivars of I. umbellata by HPLC analysis. Pigment 1 acylated with one molecule of p-coumaric acid was dominantly observed in purple-violet cultivars. On the other hand, pigments (9 and 11) acylated with three molecules of hydroxycinnamic acids were observed in lilac (purple-violet) cultivars as major anthocyanins. The bluing effect and stability on these anthocyanin colors were discussed in relation to the molecular number of hydroxycinnamic acids in these anthocyanin molecules.     

Bioactive saponins from Microsechium helleri and Sicyos bulbosus

Eleven oleanane-type saponins (1-11) have been isolated from Microsechium helleri and Sicyos bulbosus roots and were evaluated for their antifeedant, nematicidal and phytotoxic activities. Saponins {3-O-β-d-glucopyranosyl (1 → 3)-β-d-glucopyranosyl-2β,3β,16α,23-tetrahydroxyolean-12-en-28-oic acid 28-O-α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-xylopyranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranoside} (1), and {3-O-β-d-glucopyranosyl-2β,3β,16α,23-tetrahydroxyolean-12-en-28-oic acid 28-O-α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-xylopyranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranoside} (2) were also isolated from M. helleri roots together with the two known compounds 3 and 4. Seven known structurally related saponins (5-11) were isolated from S. bulbosus roots. The structures of these compounds were established as bayogenin and polygalacic glycosides using one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds 7, 10, bayogenin (12) and polygalacic acid (13) showed significant (p < 0.05) postingestive effects on Spodoptera littoralis larvae, compounds 5-11 and 12 showed variable nematicidal effects on Meloydogyne javanica and all tested saponins had variable phytotoxic effects on several plant species (Lycopersicum esculentum, Lolium perenne and Lactuca sativa). These are promising results in the search for natural pesticides from the Cucurbitaceae family.     

Bioactive polyhydroxylated sterols from the marine sponge Haliclona crassiloba

Four new polyhydroxylated sterols, named halicrasterols A–D (1–4), together with six known analogs (5–10) were isolated from the marine sponge Haliclona crassiloba. Compounds 1 and 2 represented rare examples of steroids featuring 17(20)E-double bonds. The structures of 1–10 were elucidated by spectroscopic analysis and comparison with reported data. This is the first report of a steroid profile for this species. The antimicrobial activities of 1–10 were evaluated against a panel of bacterial and fungal strains in vitro, and compounds 4 and 9 showed moderate activity against some of the Gram-positive strains with MICs ranging from 4 to 32 μg/mL.     

Synthesis of Neu5Ac-Gal-functionalized gold glyconanoparticles

Neu5Ac-Gal-containing neoglycoside 1 was convergently synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition of methyl (6-azidohexyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-O-α-d-glycero-d-galacto-2-nonulopyranosyl)uronate and 11-thioacetylundecyl 2,4,6-tri-O-benzoyl-3-O-propargyl-β-d-galactopyranoside. The stable and water-soluble gold glyconanoparticle 2 (d = 3.4 nm) has been successfully prepared from neoglycoside 1 and characterized by NMR, IR, and TEM techniques.     

Determination of the hydroxycinnamate profile of 12 members of the Asteraceae family

The hydroxycinnamates of the leaves of 12 plants of the Astreraceae family, Achillea millefolium, Arnica montana, Artemesia dracunculus, Cichorium intybus, Cnicus benedictus, Cynara scolymus, Echinops humilis, Inula helenium, Lactuca sativa, Petasites hybridus, Solidago virgaurea, and Tanacetum parthenium were investigated qualitatively by LC-MSⁿ. Thirty-nine chlorogenic acids were detected and all characterized to regioisomeric level on the basis of their fragmentation pattern in the tandem MS spectra, most of them for the first time from these sources with two of them previously not reported in nature. Both chlorogenic acids based on trans and cis-cinnamic acid substituents were identified. Assignment to the level of individual regioisomers was possible for seven caffeoylquinic acids (1-7), 11 dicaffeoylquinic acids (17-27), six feruloylquinic acids (9-14), two p-coumaroylquinic acids (15-16), two caffeoyl-feruloylquinic acids (28 and 29), four caffeoyl-p-coumaroylquinic acids (30-33), three dicaffeoyl-succinoylquinic acids (34-36), two dicaffeoyl-methoxyoxaloylquinic acids (37 and 38), and one tricaffeoylquinic acid (39). Furthermore, one caffeoylshikimic acid (40), one caffeoyltartaric acid (41), three dicaffeoyltartaric acids (42-44), and three caffeoyl-feruloyltartaric acids (45-47) were detected and shown to possess characteristic tandem MS spectra and were tentatively assigned on the basis of their retention time and previously developed hierarchical keys.     

β-Diiminatolanthanoid(III) halides revisited

The crystalline compounds [LnCl₂(L)(thf)₂] [Ln = Ce (1), Tb (2), Yb (3)], [NdI₂(L)(thf)₂] (4), [LnCl(L′)₂] [Ln = Tb (5), Yb (6) (a known compound)] and [YbCl(L′′)(μ-Cl)₂Li(OEt₂)₂] (7) have been prepared [L = {N(C₆H₃Prⁱ₂-2,6)C(H)}₂CPh, L′ = {N(SiMe₃)C(Ph)}₂CH, L′′ = {N(SiMe₃)C(C₆H₄Ph-4)}₂CH]. The X-ray molecular structures of 2-7 have been established; in each, the monoanionic ligand L, L′ or L′′ is N,N′-chelating and essentially π-delocalised. Each of 1-7 was prepared from the appropriate LnCl₃, or for 4 [NdI₃(thf)₂], and an equivalent portion of the appropriate alkali metal [Li for 7, Na for 2, 3 and 5, or K for 1, 4 and 6] β-diiminate in thf; the isolation of exclusively 5 and 6 (rather than the L′ analogues of 2 or 3) is noteworthy, as is the structure of 7 which has no precedent in Group 3 or 4f metal β-diiminato chemistry.     

Bis-sesquiterpenes and diterpenes from Chloranthus henryi

Bis-sesquiterpenes, henriols A (1), B (2), C (3), and D (4), and three diterpenes, henrilabdanes A (5), B (6), and C (7), together with two known bis-sesquiterpenes and three known labdane diterpenes, were isolated from the ethanol extract of the roots of Chloranthushenryi. Their structures and absolute configurations were elucidated by NMR spectroscopic, X-ray crystallographic and CD analyses. Compounds 1, 5, 6 and 7 showed moderate hepatoprotective activities with IC₅₀ values of 0.19, 0.66, 0.09 and 0.18 μM, respectively. They were not studied further due to the weak effects noted. Compounds 3 and 8 exhibited cytotoxic activities against three types of cancer cell lines including the hepatoma (BEL-7402), human gastric carcinoma (BGC-823), and colon cancer (HCT-8).     

Anti-inflammatory activity of constituents from Glechoma hederacea var. longituba

Rosmarinic acid, its analogues, and a phenolic compound were obtained from G. hederacea var. longituba. There were two new compounds, methyl isoferuloyl-7-(3,4-dihydroxyphenyl) lactate (1) and benzyl-4′-hydroxy-benzoyl-3′-O-β-d-glucopyranoside (4), and four known compounds (2, 3, 5 and 6). The structures of these compounds were determined on the basis of spectroscopic methods. Each compound was tested by NF-κB luciferase assay and three rosmarinic acid analogues inhibited NF-κB production and the induction of COX-2 and iNOS mRNA in HepG2 cells.     

Identification and in vitro anti-esophageal cancer activity of a series of halogenated monoterpenes isolated from the South African seaweeds Plocamium suhrii and Plocamium cornutum

Five known (1, 2, 4, 6 and 7) halogenated monoterpenes together with 1Z,3R^∗,4S^∗,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene (3) and (3R^∗,4S^∗)-3,4,6,7-tetrachloro-3,7-dimethyl-octen-1-ene (5) were isolated from the red macroalga Plocamium suhrii and their structures deduced from their spectroscopic data. The seven compounds from P. suhrii together with five related compounds from Plocamium cornutum have been evaluated for their cytotoxic effects on an esophageal cancer cell line (WHCO1). Compounds 1-6 showed greater cytotoxicity in this assay as compared to the known anticancer drug cisplatin.     

Compounds from Kadsura angustifolia with anti-HIV activity

Four new cycloartane triterpenoids, angustific acid A (1), angustific acid B (2), angustifodilactone A (3) and angustifodilactone B (4) were isolated from the branches of Kadsura angustifolia together with six known compounds, micranoic acid B (5), nigranoic acid (6), schisandrin (7), schisantherin D (8), interiotherin B (9), schisantherin B (10). Their structures were established on the basis of extensive spectroscopic data analyses and comparison with spectroscopic data reported. Compound 1, characterized by the presence of a C-16/C-17, C-20/C-21 conjugated diene and a C-1/C-7 ester bridge formed in rings A and B, provided a novel structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, the anti-HIV activities of these compounds were determined in infected C8166 cells, and it was found that angustific acid A (1) exhibited the most potent anti-HIV activity with an EC₅₀ value of 6.1 μg/mL and a therapeutic index of more than 32.8.     

Diheteroarylmethyl substituted titanocenes: A novel class of possible anti-cancer drugs

From the reaction of tert-butyl lithium or n-butyl lithium with N-methylpyrrole (1a), furan (1b) or 2-bromo-thiophen (1c), 2-N-methylpyrrolyl lithium (2a), 2-furyl lithium (2b) or 2-thiophenyl lithium (2c), respectively, was obtained. When reacted with 6-(2-N-methylpyrrolyl) fulvene (3a), 6-(2-furyl) fulvene (3b) or 6-(2-thiophenyl) fulvene (3c), the corresponding lithiated intermediates were formed (4a-c). Titanocenes (5a-c) were obtained through transmetallation with titanium tetrachloride. When these titanocenes were tested against pig kidney epithelial (LLC-PK) cells, inhibitory concentrations (IC₅₀) of 32 μM, 140 μM, and 240 μM, respectively, were observed. These values represent improved cytotoxicity against LLC-PK, compared to their ansa-analogues.     

Anthocyanins in Caprifoliaceae

The qualitative and relative quantitative anthocyanin content of 19 species belonging to the genera Sambucus, Lonicera and Viburnum in the family Caprifoliaceae has been determined. Altogether 12 anthocyanins were identified; the 3-O-glucoside (2), 3-O-galactoside (5), 3-O-(6″-O-arabinosylglucoside) (7), 3-O-(6″-O-rhamnosylglucoside) (9), 3-O-(2″-O-xylosyl-6″-O-rhamnosylglucoside) (10), 3-O-(2″-O-xylosylgalactoside) (11), 3-O-(2″-O-xylosylglucoside) (12), 3-O-(2″-O-xylosylglucoside)-5-O-glucoside (14), 3-O-(2″-O-xylosyl-6″-O-Z-p-coumaroylglucoside)-5-O-glucoside (15) and 3-O-(2″-O-xylosyl-6″-O-E-p-coumaroylglucoside)-5-O-glucoside (16) of cyanidin, in addition to the 3-O-glucosides of pelargonidin and delphinidin (1 and 3). Pigment 7 is the first complete identification of the disaccharide vicianose, 6″-O-α-arabinopyranosyl-β-glucopyranose, linked to an anthocyanidin.     

Methylated anthocyanidin glycosides from flowers of Canna indica

Methylated anthocyanin glycosides were isolated from red Canna indica flower and identified as malvidin 3-O-(6-O-acetyl-β-d-glucopyranoside)-5-O-β-d-glucopyranoside (1), malvidin 3,5-O-β-d-diglucopyranoside (2), cyanidin-3-O-(6″-O-α-rhamnopyranosyl-β-glucopyranoside (3), cyanidin-3-O-(6″-O-α-rhamnopyranosyl)-β-galactopyranoside (4), cyanidin-3-O-β-glucopyranoside (5) and cyanidin-O-β-galactopyranoside (6) by HPLC-PDA. Their structures were subsequently determined on the basis of spectroscopic analyses, that is, ¹H NMR, ¹³C NMR, HMQC, HMBC, ESI-MS, and UV-vis. Compounds (1-4) were found to be in major quantity while compounds (5-6) were in minor quantity.     

Ecdysteroids and a sucrose phenylpropanoid ester from Froelichia floridana

Phytoecdysteroid glycosides (1-5) and a phenylpropanoid ester of sucrose (6) were isolated from the whole plant of Froelichia floridana, along with eight known compounds including three ecdysteroids (7-9), four flavonoids (10-13), and one phenolic compound (14). Structures were determined using a combination of spectroscopic techniques. Compounds 1, 2 and 6-14 were tested in vitro for their activity against human DNA topoisomerase I. Compound 13 (diosmetin) showed marginal inhibition against topoisomerase I with IC₅₀ of 130 μM in conjunction with low intercalation ability.     

Synthesis and transition metal complexes of 3,3-bis(1-vinylimidazol-2-yl)propionic acid, a new N,N,O ligand suitable for copolymerisation

The new N,N,O heteroscorpionate ligand 3,3-bis(1-vinylimidazol-2-yl)propionic acid (Hbvip) (5) was synthesised in five steps starting from 1-vinylimidazole. This ligand is closely related to 3,3-bis(1-methylimidazol-2-yl)propionic acid (Hbmip), but contains two vinyl linker groups which can be used for radical-induced polymerisation reactions. The κ³-N,N,O coordination behaviour of 5 was proven by the synthesis of the tricarbonyl complexes [Re(bvip)(CO)₃] (6), [Mn(bvip)(CO)₃] (7) and [Cu(bvip)₂] (8). To obtain good yields of 6, it was synthesised in water instead of THF. The ligand as well as all three complexes were characterised by X-ray crystallography. Copolymerisation of 5 with pure methyl methacrylate (MMA) or a combination of MMA and ethylene glycol dimethacrylate (EGDMA) led to the solid phases P1 and P2. Polymer-bound rhenium and manganese tricarbonyl complexes could be obtained by the reaction of deprotonated P1 with [MBr(CO)₅] (M = Re, Mn) and also by copolymerisation of 6 and 7 with MMA. In both cases, the facial tripodal binding behaviour was evidenced by IR spectra of the polymers. Furthermore, the content of metal incorporated in the polymers was determined by elemental analysis, AAS or ICP-OES measurements. Reaction of the deprotonated solid phase P1 with copper(II) chloride led to a blue solid-phase (P1-Cu). The UV-Vis absorption maximum of P1-Cu is found at 615 nm, which is almost identical to that found for 8. Thereby, it seems likely that P1 is flexible enough to form bisligand complexes with copper(II). This means that the copper centres act as a kind of crosslinking agents. In contrast, the heterogeneous reaction of P2 with copper(II) chloride yielded a lime green solid phase (P2-Cu). The bathochromic shift of the absorption maximum by 102 nm suggests one-sided bound copper centres.     

Guaiane type sesquiterpenes and other constituents from Daucus carota L.

In a chemosystematic investigation of the fruits of Daucus carota L. we have isolated eleven compounds including four guaiane type sesquiterpenes (1–4), one eudesmane type sesquiterpene (5) and six other constituents (6–11). Among them, the five compounds 1–5 all are new for Daucus carota L. and all have been reported in Torilis japonica. The results show that Daucus carota L. is chemically similar with Torilis japonica providing chemical evidence for both species used as the same traditional Chinese medicine “nanheshi”.