Absolute configuration of tropane alkaloids from Schizanthus species by vibrational circular dichroism

The absolute configuration (AC) of 6β-hydroxy-3α-senecioyloxytropane (1), 3α-hydroxy-6β-tigloyloxytropane (2), 3α-hydroxy-6β-senecioyloxytropane (3), and 3α-hydroxy-6β-angeloyloxytropane (4) was assigned as (1R,3R,5S,6R) using density functional theory (DFT) calculations at the B3LYP/DGDZVP level of theory in combination with experimental vibrational circular dichroism (VCD) measurements and comparison with the spectra of similar tropanes. The AC of 1 followed from a sample isolated from Schizanthus grahamii, while those of the mixture of 2 and 3, isolated from the same source, were determined by comparing the VCD measurement to a weighted calculation of the individual VCD spectra according to a 69:31 ratio of 2:3 determined by ¹H NMR signal integration. In turn, Schizanthus pinnatus provided a 7:3 mixture of 1:4 whose AC was determined using the experimental VCD absorptions in the 1150-950 cm⁻¹ spectral region which were compared with those observed for 1-3 and with those described for other 3α,6β-tropanediol derivatives.     

Prenylated acetophenones from Melicope obscura and Melicope obtusifolia ssp. obtusifolia var. arborea and their distribution in Rutaceae

Four prenylated acetophenones 2,6-dihydroxy-4-geranyloxyacetophenone (1), 4-geranyloxy-2,6,β-trihydroxyacetophenone (2), 2,6-dihydroxy-4-geranyloxy-3-prenylacetophenone (3), and 4-geranyloxy-3-prenyl-2,6,β-trihydroxyacetophenone (4) have for the first time been isolated from Melicope obscura (1 and 2) and Melicope obtusifolia ssp. obtusifolia var. arborea (3 and 4). The distribution of prenylated acetophenones in Rutaceae is reviewed and the results, including the new records, indicate that prenylated acetophenones are valuable as chemotaxonomic markers for the subfamily Rutoideae, tribe Xanthoxyleae sensu Engler.     

Phomoeuphorbins A-D, azaphilones from the fungus Phomopsis euphorbiae

Four azaphilones, named phomoeuphorbins A-D (1-4) were isolated from cultures of Phomopsis euphorbiae, an endophytic fungus isolated from Trewia nudiflora. Structures of 1-4 were established on the basis of spectroscopic analyses, including application of 2D NMR spectroscopic techniques. Phomoeuphorbins A and C exhibited very weak inhibitory activities against HIV replication in C8166 cells in vitro.     

2-(1-(Dimethylamino)ethyl)phenylpalladium(II) complexes 5-functionalized with fluorous silyl tails

New fluorous-organometallics based on the chiral ligand α-methyl-N,N-dimethylbenzylamine (TMBA) were prepared by treatment of fluorous silyl bromide reagents with in situ 4-lithiated TMBA to give fluorous N,N-dimethyl(α-methyl-4-trialkylsilylbenzyl)amine ligands 1a-1c that vary in the number of fluorous tails attached to the Si atom. Ligands 1a-1c were successfully cyclo-palladated by treatment with Pd(OAc)₂/LiCl in methanol to furnish the corresponding chloride-bridged dimeric arylpalladium(II) complexes 2a-2c in good yields. The latter derivatives could be converted into monomeric Lewis-base adducts by complexation with pyridine (3a-3c), or triphenylphosphine (4a-4c). The crystal structure of triphenylphosphine complex 4a has been elucidated. To probe their fluorophilicity, the partition coefficient of each of the derivatives in the fluorous biphasic solvent (FBS) system perfluoromethylcyclohexane/n-octane has been determined.     

Virulence Gene Regulation by l-Arabinose in Salmonella enterica

Invasion of the intestinal epithelium is a critical step in Salmonella enterica infection and requires functions encoded in the gene cluster known as Salmonella Pathogenicity Island 1 (SPI-1). Expression of SPI-1 genes is repressed by l-arabinose, and not by other pentoses. Transport of l-arabinose is necessary to repress SPI-1; however, repression is independent of l-arabinose metabolism and of the l-arabinose-responsive regulator AraC. SPI-1 repression by l-arabinose is exerted at a single target, HilD, and the mechanism appears to be post-translational. As a consequence of SPI-1 repression, l-arabinose reduces translocation of SPI-1 effectors to epithelial cells and decreases Salmonella invasion in vitro. These observations reveal a hitherto unknown role of l-arabinose in gene expression control and raise the possibility that Salmonella may use L-arabinose as an environmental signal.     

5α,8α-Epidioxysterols from the gorgonian Eunicella cavolini and the ascidian Trididemnum inarmatum: Isolation and evaluation of their antiproliferative activity

Three new (1, 4, 9) and nine previously reported (2, 3, 5-8, 10-12) 5α,8α-epidioxysterols were isolated from the organic extracts of the gorgonian Eunicella cavolini and the ascidian Trididemnum inarmatum. The structures and relative configurations of 1-12 were established on the basis of detailed NMR spectroscopic analyses and comparison with the literature. The growth inhibitory effects of 1-12 were evaluated against MCF-7 human breast cancer cells. Compound 1, bearing a cyclopropyl moiety in the side chain, exhibited the highest antiproliferative activity.     

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.     

Oxygenated verticillene derivatives from Bursera suntui

Medium polarity fractions of the hexane extracts of the stems of Bursera suntui afforded six previously known (1-6) and four hitherto unknown verticillane derivatives: (1S,3Z,7S,8S,11S,12S)-(+)-7,8-epoxyverticill-3-en-12,20-diol (7), (1S,3Z,7S,8S,11S,12S)-(+)-7,8-epoxyverticill-3-en-12,20-diol 20-acetate (8), (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol (9), and (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol 20-acetate (10). Acetylation of 9 and 10 yielded (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol 7,20-diacetate (11), while hydrolysis of 8 gave 7. The structures and stereochemistry of 7-11 were established by spectroscopic analyses, particularly by 1D and 2D NMR spectra and HRESIMS. The conformational preferences of 7-11 were studied by molecular mechanics modelling employing the Monte Carlo protocol followed by B3LYP/DGDZVP DFT calculation, thus supporting the observed ¹H NMR NOESY cross peaks.     

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.     

Sesquiterpene constituents from the essential oils of the liverworts Mylia taylorii and Mylia nuda

The essential oils and extracts of Mylia taylorii and M. nuda were investigated by gas chromatography, mass spectrometry, NMR spectroscopy and chemical correlations. Beside several known compounds 13 new constituents including three new carbon skeletons could be identified. Four hydrocarbons with a molecular formula of C₁₅H₂₂ (m/z 202) were identified as myli-4(15)-ene (1), aromadendra-1(10),4(15)-diene (19), aromadendra-4,10(14)-diene (20) and aromadendra-4,9-diene (21). Three oxaspiro-compounds were identified as 7-epi-bourbon-3-en-5,11-oxide (22), guai-3,10(14)-dien-5,11-oxide (23) and guai-3,9-dien-5,11-oxide (24). The absolute configuration of myli-4(15)-en-3-one (5) could be established by chemical correlation. Together with α-taylorione (7) the corresponding 6,11-seco-compound taylopyran (25) with a new carbon skeleton was identified which serves as a precursor to taylocyclane (26) and taylofuran (27). Taynudol (28) contains a new carbon skeleton with a cyclobutenyl structure.     

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.     

Khayanolides from African mahogany Khaya senegalensis (Meliaceae): A revision

Five khayanolides (1-O-acetylkhayanolide B 1, khayanolide B 2, khayanolide E 3, 1-O-deacetylkhayanolide E 4, 6-dehydroxylkhayanolide E 5) were isolated from the stem bark of African mahogany Khaya senegalensis (Meliaceae). Their structures and absolute configurations were determined through extensive spectroscopic analyses including MS, NMR, and single-crystal X-ray diffraction experiments. The results established that two previously reported khayanolides, 1α-acetoxy-2β,3α,6,8α,14β-pentahydroxy-[4.2.1^10,30.1^1,4]-tricyclomeliac-7-oate 6 and 1α,2β,3α,6,8α,14β-hexahydroxy-[4.2.1^10,30.1^1,4]-tricyclomeliac-7-oate 7, were, in fact, 1-O-acetylkhayanolide B 1 and khayanolide B 2, and that the two reported phragmalin derivatives, methyl 1α-acetoxy-6,8α,14β,30β-tetrahydroxy-3-oxo-[3.3.1^10,2.1^1,4]-tricyclomeliac-7-oate 8 and methyl 1α,6,8α,14β,30β-pentahydroxy-3-oxo-[3.3.1^10,2.1^1,4]-tricyclomeliac-7-oate 9, were, in fact, khayanolide E 3 and 1-O-deacetylkhayanolide E 4, respectively. Based on the results from this study and consideration of the biogenetic pathway, the methyl 6-hydroxyangolensate in African mahogany K. senegalensis should have a C-6 S configuration while methyl 6-hydroxyangolensate in genuine mahogany Swietenia species should have a C-6 R configuration.     

Synthesis and characterization of platinum(IV) complexes with N,S and S,S heterocyclic ligands

The reactions of [PtMe₃(OAc)(bpy)] (4) with the N,S and S,S containing heterocycles, pyrimidine-2-thione (pymtH), pyridine-2-thione (pytH), thiazoline-2-thione (tztH) and thiophene-2-thiol (tptH), resulted in the formation of the monomeric complexes [PtMe₃(-κS)(bpy)] ( = pymt, 5; pyt, 6; tzt, 7; tpt, 8), where the heterocyclic ligand is coordinated via the exocyclic sulfur atom. In contrast, in the reactions of [PtMe₃(OAc)(Me₂CO)_x] (3, x = 1 or 2) with pymtH, pytH, tztH and tptH dimeric complexes [{PtMe₃(μ-)}₂] (μ- = pymt, 9; pyt, 10; tzt, 11) and the tetrameric complex [{PtMe₃(μ₃-tpt-κS)}₄] (12), respectively, were formed. The complexes were characterized by microanalyses, ¹H and ¹³C NMR spectroscopy and negative ESI-MS (12) measurements. Single-crystal X-ray diffraction analysis of [PtMe₃(pymt-κS)(bpy)] (5) exhibited a conformation where the pymt ligand lies nearly perpendicular to the complex plane above the bpy ligand that was also confirmed by quantum chemical calculations on the DFT level of theory.     

Kuguacins F-S, cucurbitane triterpenoids from Momordica charantia

Chemical investigation of the vines and leaves of Momordica charantia resulted in isolation of fourteen cucurbitane triterpenoids, kuguacins F-S (1-14), including two pentanorcucurbitacins (6 and 7), one octanorcucurbitacin (8), and two trinorcucurbitacins (11 and 12), along with six known analogues. Their structures were elucidated on the basis of extensive spectroscopic and single-crystal X-ray diffraction analyses. Compounds 1-14 exhibited weak anti-HIV-1 activities in vitro.     

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 regioisomeric 17β-N-phenylpyrazolyl steroid derivatives and their inhibitory effect on 17α-hydroxylase/C17,20-lyase

The reaction of 3β-hydroxy-21-hydroxymethylidenepregn-5-en-3β-ol-20-one (1) with phenylhydrazine (2a) affords two regioisomers, 17β-(1-phenyl-3-pyrazolyl)androst-3-en-3β-ol (5a) and 17β-(1-phenyl-5-pyrazolyl)androst-5-en-3β-ol (6a). The direction of the ring-closure reactions of 1 with p-substituted phenylhydrazines (2b-e) depends strongly on the electronic features of the substituents. Oppenauer oxidation of 3β-hydroxy-17β-exo-heterocyclic steroids 5a-e and 6a-e yielded the corresponding Δ⁴-3-ketosteroids 9a-e and 10a-e. The inhibitory effects (IC₅₀) of these compounds on rat testicular C_17,20-lyase were investigated by means of an in vitro radioligand incubation technique.     

Aspergilones A and B, two benzylazaphilones with an unprecedented carbon skeleton from the gorgonian-derived fungus Aspergillus sp

Two novel benzylazaphilone derivatives with an unprecedented carbon skeleton, aspergilone A (1), and its symmetrical dimer with a unique methylene bridge, aspergilone B (2), have been isolated from the culture broth of a marine-derived fungus Aspergillus sp. from a gorgonian Dichotella gemmacea. Their structures and relative stereochemistries of 1 and 2 were elucidated using a combination of NMR spectroscopy and X-ray crystallography. Compound 1 not only exhibited in vitro selective cytotoxicity but also showed potent antifouling activity.     

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.     

Steroidal alkaloid saponins and steroidal saponins from Solanum surattense

A rare 16β-H steroidal alkaloid saponin (1), an avenacoside-type saponin (2), two steroidal saponins (4, 5), one revised-structure steroidal saponin (3) and six known compounds (6-11) were isolated from aerial parts of Solanum surattense Burm. f. Their structures were established on the basis of physical data, as well as by using spectroscopic (HRESIMS, 1D and 2D NMR), and chemical analysis methods. Compounds 1 and 11 showed cytotoxicity against A549 cell line with IC₅₀ values of 20.3 and 15.7 μM, respectively.     

Synthesis, characterization of [{(N-methyl-N-benzyl)amino}methyl]ferrocenes and their cyclopalladated complexes: Crystal structure of σ-Pd[(η-C5H5)Fe(η-C5H3CH2N(CH3)CH2C6H4NO2-4)]Cl(PPh3)

Condensation of aminomethylferrocene (1) and substituted benzaldehydes resulted in aldimines 2a-c which followed by reduction with sodium borohydride to give 3a-c. N-methylation of 3a-c with HCHO/NaCNBH₃/HOAc led to 4a-c. Treatment of 4a-c with sodium palladium tetrachloride in the presence of sodium acetate afforded cleanly cyclopalladated 5a-c in which configurations consisted of the R_NR_C, S_NS_C. The preferable activation of C_Ferrocenyl-H bond over C_Phenyl-H bond was also observed. All compounds 2-5 were characterized by elemental analysis, IR and ¹H NMR. In addition, the molecular structure of 5c was confirmed by single crystal X-ray diffraction. The possible mechanism for the formation of 5 was also discussed.