Stereochemical challenges in characterizing nitrogenous spiro-axane sesquiterpenes from the Indo-Pacific sponges Amorphinopsis and Axinyssa

An investigation was conducted to identify the structures and bioactive properties of five compounds isolated from the Halichondrida sponges Amorphinopsis foetida and Axinyssa aplysinoides. All compounds possessed the spiro-axane sesquiterpene core and all were substituted at C-2 with nitrogen containing functionality. The stereochemistry of one known compound has been revised to (2R,5R,10S)-2-formamido-6-axene (3). It exhibited mild selective solid tumor and mild antibacterial activity and was found from Axinyssa. A second known substance whose stereochemistry has also been revised, (2R,5R,10S)-2-isothiocyanato-6-axene (4) plus its undescribed diastereomer (5) were isolated from Amorphinopsis. Both sponges were the source of two new N-phenethyl-2-formamido-6-axene diastereomeric compounds 6 and 7. No solid tumor or antibacterial activity was found for 4-7.     

Kunzeanones A, B, and C: novel alkylated phloroglucinol metabolites from Kunzea ambigua

Three new metabolites, kunzeanones A (1), B (2), and C (3), along with three known compounds, cryptostrobin (4), (+)-spathulenol (5), and (−)-globulol (6), were isolated from the non-polar fraction of the dried leaves of Kunzea ambigua (Myrtaceae), which shows ichthyotoxicity toward a small fish, medaka. The structures of these new compounds were elucidated as condensates of alkylated phloroglucinol with methylflavanone and germacrane-type sesquiterpene, respectively, on the basis of spectral analyses including 1-D and 2-D NMR spectra. The stereochemistries of kunzeanones A and B were determined by X-ray crystallographic analysis. A sesquiterpene, (+)-spathulenol (5), among the isolates was characterized as the ichthyotoxic principle of the extract.     

Chemical and genetic diversity of Ligularia virgaurea collected in northern Sichuan and adjacent areas of China. Isolation of 13 new compounds

Root chemicals and DNA sequences were analyzed for Ligularia virgaurea collected in the northern Sichuan Province and adjacent areas of China. Thirty-eight samples were found to contain five chemotypes, two known and three new ones. From samples of the new chemotypes, 13 new compounds were isolated, including 3 sesquiterpene dimers and some rearranged eremophilanes. The DNA sequences suggested that the chemotype differentiation had a genetic origin.     

New sesquiterpenes from the red alga Laurencia microcladia

Three new aromatic sesquiterpenes (1, 2, and 4), one new dimeric sesquiterpene of the cyclolaurane-type (3), one sesquiterpene alcohol of bisabolene type (8) along with three previously reported metabolites (5-7), were isolated from the organic extracts of Laurencia microcladia, collected from the Chios island in the North Aegean Sea. The structures of the new natural products, as well as their relative stereochemistries, were established by means of spectral data analyses, including 2D experiments. The cytotoxicity of the isolated metabolites was evaluated against five human tumor cell lines.     

Unusual sesquiterpene glucosides from Amaranthus retroflexus

Implementing the phytochemical study of the weed Amaranthus retroflexus, four new sesquiterpene glucosides were isolated from the methanolic extract of the plant. The structures of these metabolites are determined on the basis of the mass spectrometry, and 1D and 2D NMR spectroscopies (DQ-COSY, TOCSY, HSQC, HSQC-TOCSY, HMBC, and NOESY). Two compounds are characterized by a new aglycone and differed from the site of glucosylation. The other two compounds are dimeric diastereoisomers.All the glucoside sesquiterpenes were tested on the wild species Taraxacum officinale to evaluate the role of this weed in the habitat and on the seed of A. retroflexus to verify the potential autotoxic effect of the plant.     

New cytotoxic sesquiterpenes from the red algae Laurencia obtusa and Laurencia microcladia

Three new sesquiterpenes (1-3), along with five known (5-9), were isolated from the organic extract of the red alga Laurencia obtusa, collected from the coastal rocks of Serifos in the Aegean Sea. A new dimeric sesquiterpene of the cyclolaurane-type (4) along with four previously reported (7, 10-12) metabolites, were isolated from the extract of Laurencia microcladia, collected at Chios island in the North Aegean Sea. The structures and the relative stereochemistry of the compounds are proposed on the basis of their spectral data. The cytotoxicity of the isolated metabolites was evaluated against several cell lines including human tumor cell lines.     

Pseudoguaiane-type sesquiterpenes and inhibitors on nitric oxide production from Dichrocephala integrifolia

Three new pseudoguaiane-type sesquiterpenes, dichrocepholides A-C, and two new pseudoguaiane-type sesquiterpene dimers, dichrocepholides D and E, were isolated from the aerial part of Dichrocephala integrifolia. Their stereostructures were determined on the basis of chemical and physicochemical evidence. In addition, the extract and its principal sesquiterpene constituent, parthenin, showed an inhibitory activity on nitric oxide (NO) production and on induction of inducible NO synthase.     

Neolemnane and eremophilane sesquiterpenoids from the pacific soft coral lemnalia africana

Two new sesquiterpenoids of the unprecedented neoiemnane ring system, and one eremophflane-derived sesquiterpene diol have been isolated from the pacific soft-coral Lemnalia africana. The structure of the novel neolemnane compounds, 4 and 5, were confirmed by X-ray crystallography, and the diol, 6, has been described based upon spectral analysis and chemical modification.     

13-Chloro-3-O-β-d-glucopyranosylsolstitialin from Leontodon palisae: the first genuine chlorinated sesquiterpene lactone glucoside

Apart from a number of known sesquiterpenoids, a novel chlorinated sesquiterpene lactone glucoside--13-chloro-3-O-β-d-glucopyranosylsolstitialin--has been isolated from the Southwestern European plant Leontodon palisae (Asteraceae, tribe Lactuceae). The structure has been established by high resolution mass spectrometry and 1D as well as 2D NMR spectroscopy. The compound represents the first naturally occurring chlorinated sesquiterpene lactone glucoside. The cytotoxicity of the new compound and related ones was evaluated using the MTT assay.     

Pestalustaines A and B,unprecedented sesquiterpene and coumarin derivatives from endophytic fungus Pestalotiopsis adusta

Pestalustaines A (1) and B (2), one unique sesquiterpene possessing an unusual 5/6/7-fused tricyclic ring system and one unprecedented coumarin derivative bearing 6/6/5/5-fused tetracyclic ring system, were isolated from the plant-derived Pestalotiopsis adusta. Their structures with absolute configurations were established by extensive NMR analysis, X-ray crystallography, and CD spectra associated with TD-DFT calculation. Hypothetical biosynthetic pathways for compounds 1 and 2 are proposed. Compounds 1 and 2 showed weak to moderate cytotoxic activities against three human tumor cell lines HeLa, HCT116, and A549, whose IC₅₀ values were ranged from 21.01 to 55.43?μM.     

Ecological leads for natural product discovery: novel sesquiterpene hydroquinones from the red macroalga Peyssonnelia sp.

Pharmacologically-motivated marine natural product investigations have yielded a large variety of structurally unique compounds with interesting biomedical properties, but the natural roles of these molecules often remain unknown. While secondary metabolites may function as antimicrobial chemical defenses, few studies have examined this hypothesis. In the present investigation, chromatographic fractions from 69 collections of Fijian red macroalgae representing at least 43 species were evaluated for growth inhibition of three microbial pathogens and saprophytes of marine macrophytes. At least one microbe was suppressed by fraction(s) of all evaluated algae, suggesting that antimicrobial defenses are common among tropical seaweeds. From these leads, peyssonoic acids A-B (1-2), novel sesquiterpene hydroquinones, were isolated from the crustose red alga Peyssonnelia sp. At ecologically realistic concentrations, both compounds inhibited growth of Pseudoalteromonas bacteriolytica, a bacterial pathogen of marine algae, and Lindra thalassiae, a fungal pathogen of marine algae, and exhibited modest antineoplastic activity against ovarian cancer cells. The peyssonoic acids included one novel carbon skeleton and illustrated the utility of ecological studies in natural product discovery.     

Novel sesquiterpenes and norergosterol from the soft corals Nephthea erecta and Nephtheachabroli

Chemical investigations on the acetone extract of the Formosan soft coral Nephthea erecta have afforded a new calamenene-type sesquiterpene with a mercaptan group at C-15, erectathiol (1), and a previously reported sesquiterpenoid, (+)-trans-calamenene (2). A novel sec-germacrane sesquiterpene (3), along with a novel norergosterol, chabrosterol (4), possessing a 19-norergostane skeleton, was isolated from the other soft coral Nephthea chabroli. The structures of these metabolites were elucidated through extensive spectroscopic analyses. In vitro anti-inflammatory activity of 1 and 4 (10 μM) significantly reduced the levels of the iNOS protein (58.0 ± 6.5% and 12.4 ± 2.9%) and COX-2 protein (108.7 ± 4.5% and 45.2 ± 5.4%). In addition, metabolite 1 (166 μg/disk) exhibited antimicrobial activities against a small panel of bacterial strains.     

Nor-dehydrodeguelin and nor-dehydrorotenone, C22 coumaronochromones from Lonchocarpus nicou

Lonchocarpus nicou roots lipophile extract yielded, among isoflavonoids, two coumaronochromones isomers. Spectroscopic analysis assigned the structure of nor-dehydrodeguelin to the former and (−)-nor-dehydrorotenone to the latter, the two products only differing by the cyclization of the C₅ side chain. Biogenetically, the two compounds could be considered as resulting either from cyclization of the corresponding 2′-hydroxyisoflavones and/or from oxidative ring-B contraction of the dehydrorotenoids parents.     

Synthesis of substituted [1,3]thiazolo[4,5-b]pyridines and [1,3]thiazolo[4,5-d][1,2,3]triazines

In this work, we described an easy preparation of substituted 4-amino-5-cyano-1,3-thiazoles. These compounds have been used as starting materials to obtain two classes of compounds. New substituted [1,3]thiazolo[4,5-e]pyridines were synthesized in one step via Friedländer reaction. Diazotation of 4-amino-5-cyano-1,3-thiazoles afforded 4-chloro[1,3]thiazolo[4,5-d][1,2,3]triazines in one step. The later was substituted by a secondary amine to obtain substituted 4-amino[1,3]thiazolo[4,5-d][1,2,3]triazines.     

Lacitemzine, a novel sesquiterpene acid from the Tunisian plant Pulicaria laciniata (Coss. et Kral.) Thell.

The flowers of Pulicaria laciniata (Coss. et Kral.) Thell. (Asteraceae) afforded a new sesquiterpene acid 1, named lacitemzine together with the three known compounds, 4-hydroxy-3-methoxypyridine 2, β-sitosterol-3-O-β-d-glucoside 3 and 1,3,5-trimethoxybenzene 4. The structure of compound 1, 2-(2,6-dimethyl-3,4,5,6,7,8,9,10-octahydro-5,8-oxaazulen-9-yl)acrylic acid, contains a guaiane skeleton and was elucidated by spectroscopic procedures including 2D-NMR and X-ray diffraction.     

6-endo Versus 5-exo radical cyclization: streamlined syntheses of carbahexopyranoses and derivatives by 6-endo-trig radical cyclization

Three factors that can direct 6-endo radical cyclization over 5-exo ring closure: substitution at C-5, vinyl radical cyclization and ring strain, have been considered in the context of the preparation of carbapyranoses from carbohydrate derivatives. As a result, alkyl radicals in substrates containing a strain inducing 2,3-O-isopropylidene ring, and vinyl radical in non-strained compounds undergo a completely regioselective 6-endo-trig ring closure leading to carbasugar derivatives.     

Two lignans,one alkaloid,and flavanone from the twigs of Feroniella lucida

Four new compounds, two lignans; lucidenal and lucidanin (1 and 2), one alkaloid (3), and one flavanone (4) together with 26 known compounds (5–30), were isolated from the twigs of Feroniella lucida. The structures of the new compounds were determined on the basis of spectroscopic analyses. Lucidenal 1 showed cytotoxicity against HuCCA-1, A549, MOLT-3 and HepG2 cancer cell lines with IC₅₀ values of 4.27, 9.59, 2.31, and 6.50 μg/mL, respectively. A plausible biosynthetic pathway of 1 was proposed.     

Synthesis and chromatographic study of methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d-ribofuranoside

The synthesis of two riboside-containing arsenic compounds, methyl-2,3-O-isopropylidene-5-dimethyl-arsinoyl-β-d-ribofuranoside and methyl-2,3-O-isopropylidene-5-deoxy-5-dimethyl-thioarsinoyl-β-d- ribofuranoside is presented in this paper. Intermediates and final products of the synthesis were examined by gas chromatography and thin layer chromatography. The purity of the products was assessed by NMR spectroscopy. Trimethylsilylation was used to volatilise sugar compounds and thus use of the costly HPLC–MS technique was avoided. The results affirmed the presence of tautomers in case of arsenosugars.     

Three practical approaches for the synthesis of novel 4,7-dihetarylpyrazolo[1,5-a][1,3,5]triazines

Novel 4,7-dihetarylpyrazolo[1,5-a][1,3,5]triazines were synthesized from three different approaches. The first one, involved a one-step reaction between 5-amino-3-hetaryl-1H-pyrazoles and O,S-diethyl hetaroylimidothiocarbonates or S,S-diethyl hetaroylimidodithiocarbonates under solvent-free conditions employing microwave irradiation as the energy source. In the second approach, conventional heating under reflux in DMF as solvent was used instead of the microwave irradiation; and the third one was achieved from a two-step sequence through the treatment of 5-amino-3-hetaryl-1H-pyrazoles with hetaroyl isothiocyanates and the subsequent S-alkylation and cyclization process in DMF as solvent. Some intermediates were isolated and characterized to support the regiochemistry of the studied reactions. The structures of the new compounds were unambiguously established by spectroscopic and analytical techniques.     

Mono- and sesquiterpenoids of the oleoresin ofPinus koraiensis andP. pumila. crystal structure of 1β,4αH,7αH,10βH-Guaiane-5α,14-diol

The composition of the mono- and sesquiterpenoids of the oleoresin of two species of conifers of thePinaceae family has been studied. In the oleoresin ofPinus koraiensis Sieb. et Zucc. 10 oxidized monoterpenoids, 18 sesquiterpene hydrocarbons, and six sesquiterpene alcohols have been identified. In theoleoresin ofPinus pumila (Pall.) Rg1. 10 monoterpene hydrocarbons, six oxidized monoterpenoids, 14 sesquiterpene hydrocarbons, and four sesquiterpene alcohols have been found. The structure of 1β,4αH,7αH,10βH-guaiane-5α,14-diol, one of the hydroboration-oxidation products of an unidentified sesquiterpene alcohol isolated from both oleoresins, has been determined by x-ray structural analysis.