Smectic E,C and A free radicals

Some new paramagnetic liquid crystals are described. Their mesophases have been identified, by isomorphism with known phases, as smectic mesophases of types S_E, S_C and S_A.     

Total synthesis of (+)-Z-deoxypukalide, a furanobutenolide-based cembranoid isolated from the pacific octocoral Leptogorgia spp.

A total synthesis of (+)-Z-deoxypukalide 3 using a combination of Stille and Nozaki-Hiyama-Kishi(NHK) coupling reactions as key steps, is described. During this study a new practical synthesis of the substituted butenolide intermediate 10, based on a combination of RCM and CM reactions from the cyclobutene ester 21 in the presence of 2-methylpropenol was also developed. Attempts to apply the intramolecular NHK reaction to the substrates 8a and 8b containing an ester group adjacent to the reacting aldehyde functionality gave disappointing low yields (<6%) of the corresponding coupled products 9. The synthetic (+)-Z-deoxypukalide 3 was correlated with naturally derived material, and also with pukalide 1, the first member of the furanobutenolide-based cembranoids to be isolated from corals.     

Cembrenene and mayol,two new cembranoid diterpenes from the soft coral sinularia mayi

Two new cembranoid diterpenes, cembrenene (1) and mayol (2), have been isolated from Sinularia mayi L?ttschw, along with the first reported cembrene (3) from marine organism. The structures were determined from spectral data and chemical transformations.     

Deconvolution of E/Z tetrahydroisoquinoline amide rotamers and conformers from a marine-derived Streptomyces strain

A collaborative program to discover new specialized metabolites from aquatic environments of Iceland led to the deconvolution of tetrahydroisoquinoline amide E/Z rotamers [(E/Z)-N-acetyl-MY336-a; 1] and conformers produced by a Streptomyces sp. All structures were elucidated by NMR and MS analysis, and interpretation of electronic circular dichroism (ECD) data. ECD and optical rotation (OR) simulations permitted the unequivocal assignment of the absolute configuration of compound 1 and provided an important example of delineating the spectroscopic contributions of equilibrating rotamers and boat/chair conformers of a common natural product scaffold.     

Novel cytotoxic nine-membered macrocyclic polysulfur cembranoid lactones from the soft coral Sinularia sp.

One novel nine-membered macrocyclic polysulfur cembranoid lactone, sinulariaoid A (1); three new multioxygenated cembranoids, sinulariaoid B (2), sinulariaoid C (3), sinulariaoid D (4); and four known cembranoids, capilloloid (5), dihydrosinularin (6), sinularin (7), and dihydrosinuflexolide (8) were isolated from the soft coral Sinularia sp. collected off of Sanya Bay in the South China Sea. Their stereochemical structures were determined on the basis of extensive spectroscopic methods, including single crystal X-ray diffraction analysis. Sinulariaoid A (1) is the first reported nine-membered macrocyclic polysulfur cembranoid from soft coral. The cytotoxic activities of compounds 1–8 were determined in four human cancer cell lines (HepG2, HepG2/ADM, MCF-7, and MCF-7/ADM). Of these, sinulariaoid A (1) exhibited the most potent anticancer activity in vitro, and its cytotoxicity in HepG2/ADM was more potent than in the other three cell lines. Furthermore, it was found that sinulariaoid A (1) induced apoptosis, and its selective toxicity toward HepG2/ADM cells was not related to P-glycoproteins.     

New 8-hydroxybriarane diterpenoids from the gorgonians Junceella juncea and Junceella fragilis (Ellisellidae)

Four new 8-hydroxybriarane diterpenoids, including junceols A-C (1-3) and fragilide D (4), have been isolated from the gorgonian corals Junceella juncea and Junceella fragilis, respectively. The structures of briaranes 1-4 were elucidated by the interpretations of spectral data analysis. Briaranes 1-3 have displayed inhibitory effects on superoxide anion generation by human neutrophils.     

Membrane chromatography: Protein purification from E. coli lysate using newly designed and commercial anion-exchange stationary phases

This contribution describes the purification of anthrax protective antigen (PA) protein from Escherichia coli lysate using bind-and-elute chromatography with newly designed weak anion-exchange membranes. Protein separation performance of the new AEX membrane adsorber was compared with the commercial Sartobind^® D membrane adsorber and HiTrap™ DEAE FF resin column under preparative scale conditions. Dynamic protein binding capacities of all three stationary phases were determined using breakthrough curve analysis. The AEX membrane showed higher binding capacities than the Sartobind^® D membrane at equivalent volumetric throughput and higher capacities than the HiTrap™ DEAE FF resin column at 15 times higher volumetric throughput. Anion-exchange chromatography was performed using all three stationary phases to purify PA protein. Quantitative SDS-PAGE analysis of effluent fractions showed that the purity of PA protein was higher for membrane adsorbers than the HiTrap™ DEAE FF resin column and was the same for the new AEX membrane and Sartobind^® D membrane adsorbers. The effects of E. coli lysate load volume and volumetric flow rate on PA protein separation resolution using the membrane adsorbers were minor, and the peak elution profile remained un-changed even under conditions where >75% of the total protein dynamic binding capacity of the membranes had been utilized. PA protein peak resolution was higher using pH-gradient elution than with ionic strength gradient elution. Overall, the results clearly demonstrate that membrane chromatography is a high-capacity, high-throughput, high-resolution separation technique, and that resolution in membrane chromatography can be higher than resin column chromatography under preparative conditions and at much higher volumetric throughput.     

Laurefurenynes A-F, new Cyclic Ether Acetogenins from a Marine Red Alga, Laurencia sp.

We report here on the discovery and structure determination of three new diastereomeric pairs of cyclic ether acetogenins, laurefurenynes A-F, isolated from the aqueous extract of the alga Laurencia sp. collected in the Philippines. Extensive use was made of NMR spectroscopic data and high resolution MS to determine the structures of the pure compounds. The most stable and the lowest energy conformation was determined using molecular modelling, and their cytotoxic activity was tested against different tumour cells, a significant indication that laurefurenyne C and F are moderately cytotoxic, but non-selective whilst the others are inactive.     

Marine bacterial inhibitors from the sponge-derived fungus Aspergillus sp.

Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium, yielded a new tryptophan derived alkaloid, 3-((1-hydroxy-3-(2-methylbut-3-en-2-yl)-2-oxoindolin-3-yl)methyl)-1-methyl-3,4-dihydrobenzo[e][1,4]diazepine-2,5-dione (1), and a new meroterpenoid, austalide R (2), together with three known compounds (3–5). The structures of the new compounds were unambiguously elucidated on the basis of extensive one and two-dimensional NMR (¹H, ¹³C, COSY, HMBC, and ROESY) and mass spectral analysis. Interestingly, the compounds exhibited antibacterial activity when tested against a panel of marine bacteria, with 1 selectively inhibiting Vibrio species and 2 showing a broad spectrum of activity. In contrast, no significant activity was observed against terrestrial bacterial strains and the murine cancer cell line L5178Y.     

Marine natural products: fistularin-1, -2 and -3 from the sponge Aplysina fistularis forma fulva

Three new high molecular weight bromotyrosine-related metabolites, $\text{3a}$, $\text{4a}$ and $\text{5a}$, were isolated from the sponge Aplysina ( Verongia) fistularis forma fulva, and their structures were determined from high resolution ¹H NMR and other spectroscopic data. The new metabolites are formally derived by combination of major segments of two known Aplysina metabolites $\text{1a}$ and $\text{2}$.     

Absolute stereochemistry of antifouling cembranoid epimers at C-8 from the Caribbean octocoral Pseudoplexaura flagellosa. Revised structures of plexaurolones

Eight cembranoid epimers at C-8 (1-8) were isolated from the organic extract of the Colombian Caribbean octocoral Pseudoplexaura flagellosa. Compounds 2, 4, and 6 are reported for the first time. Although compounds 1, 3, 5, 7, and 8 have been reported previously, their structures and NMR assignments are revised, completed or corrected. The structures of these compounds were established on the basis of detailed analysis of their spectroscopic data. Furthermore, the relative configurations of compounds 1-3 and 7 were confirmed by single-crystal X-ray diffraction. The absolute configurations of compounds 1-8 were determined using a combination of the modified Mosher method and unambiguous chemical interconversions. Evaluation of their antifouling properties using quorum sensing inhibition (QSI) and biofilm inhibition bioassays showed that compounds 3, 6, and 7 have excellent QSI activity against Chromobacterium violaceum, as measured by inhibition of the production of violacein pigment, without interfering with its growth. Furthermore, compounds 3, 5, 6, and 8 exhibited inhibition of biofilm maturation without interfering in the growth of Pseudomonas aeruginosa, Vibrio harveyi, and Staphylococcus aureus. This is the first report of cembranoids as inhibitors of bacterial biofilm and as compounds that interfere with QS in C. violaceum.     

Natural anti-HIV agents. Part 3: Litseaverticillols A-H, novel sesquiterpenes from Litsea verticillata

Bioassay directed-fractionation led to the identification of litseaverticillols A-H (1-8) from the leaves and twigs of Litsea verticillata Hance. These new sesquiterpenes possess a unique skeleton that was recently designated as ‘litseane’. The structures of these compounds were determined by spectroscopic means including 1D and 2D NMR data. Structural configurations were determined by ROESY experiments. Mosher ester reactions and optical rotation measurements established the sesquiterpenes 1-8 as racemates. Isolates 1-8 inhibited HIV-1 replication in HOG.R5 cells with IC₅₀ values ranging from 2 to 15 μg/ml (8-58 μM) while affecting the growth of HOG.R5 at concentrations 2-3-fold higher. Based on this data, structure-activity relationships can be discerned, suggesting compounds of this class are good candidates for analog production.     

Bacterial detection using carbohydrate-functionalised CdS quantum dots: a model study exploiting E. coli recognition of mannosides

Mannose-coated CdS quantum dots (Man-QDs) were prepared in a facile aqueous, one-pot process that exploits the self-assembly of thiolated mannose in the presence of CdS under reducing conditions. The resulting ∼15 nm diameter nanoparticles produce an intense, broad luminescence emission centred at 550 nm. These Man-QDs induce luminescent aggregates of Escherichia coli which can be used to detect bacteria in cell suspensions containing as few as 10⁴E. coli per mL. The aggregation process is dependent on the E. coli cell surface FimH mannose-specific lectin. The recognition and subsequent detection of the E. coli using the Man-QD has been shown to be specific as aggregation does not occur either with an E. coli strain defective in the FimH lectin or with galactose-coated QDs.     

Sol-gel luminescence biosensors: Encapsulation of recombinant E. coli reporters in thick silicate films

A class of sensing elements based on the encapsulation of genetically engineered bioluminescent Escherichia coli (E. coli) reporter strains in sol-gel derived silicates is described. We demonstrate the concept by the immobilization of these bacterial cells in thick silicate films. Heat shock, oxidative stress, fatty acids, peroxides, and genotoxicity reporting bacteria were incorporated in the sol-gel silicates and their luminescence response was compared to that of the non-immobilized culture. All the immobilized bacteria maintained viability and luminescence activity for several months. The bacteria-silicate hybrids can be used either as disposable sensors or in multiple use sensing test-kits, and they can be also integrated in early warning devices operated in continuous flow conditions.     

Microwave-assisted solid phase synthesis of Imatinib, a blockbuster anticancer drug

An expeditious, high yield and convenient synthesis of Imatinib was carried out on an aldehydic, super acid-sensitive resin, through an efficient, microwave-assisted synthetic protocol. The high versatility of the reaction scheme may enable the straightforward preparation of libraries of potential protein kinase inhibitors endowed with large molecular diversity.     

Fourier transform infrared microspectroscopy as a bacterial source tracking tool to discriminate fecal E. coli strains

The aim of this work was to use the FT-IR microspectroscopy technique, a union of a FT-IR spectrometer with a microscope, to discriminate fecal Escherichia coli strains from cows, chickens and humans and to compare the efficiency of this method with the genomic fingerprinting method, BOX-PCR. The obtained BOX-PCR profiles were able to correctly discriminate 93.75% of the chicken strains, 80% of the cow strains and 65% of the human strains. An efficient PLS-DA model was developed, using orthogonal signal correction and the second derivate of the FT-IR spectra. This model allowed the correct discrimination, according to the animal source, of all the E. coli strains analyzed. The bands in the FT-IR spectra that were responsible for the strains discrimination were in the region between 2816 and 3026 cm⁻¹ wavenumber, described as fatty acids. It was demonstrated that FT-IR microspectroscopy can be a suitable tool for fecal E. coli discrimination, because it is fast, easy to carry out and presents a flexible discrimination power.     

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.