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Glycosylation reactions of the ethylthio, bromo and chloro derivatives of 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranose were studied applying different acceptors under different conditions. Elimination side-reactions affording exo- and endoglycals occured in all cases, however, with different proportions. Glycosyl chloride donor was applied to glycosylate a trisaccharide acceptor obtaining a new sulfonic acid mimetic of the sialyl Lewis X tetrasaccharide in high yield.

Chromatographic separation of a crude extract obtained from the fungus Aspergillus sp., isolated from the Mediterranean sponge Tethya aurantium, yielded five new meroterpenoid metabolites, austalides M–Q (1–5), together with nine known compounds (6–13). The structures of the new compounds were unambiguously elucidated on the basis of extensive 1D and 2D NMR methods and by mass spectral analysis. Furthermore, the absolute configurations of 1 and 4 were determined by time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations, allowing the assignment of the absolute configuration of analogous compounds 2, 3, and 5. The calculations revealed that the conformation of the benzene-fused phthalide chromophore, which is sensitive to even minor changes in its proximity, is decisive for the ECD parameters, rendering a simple ECD comparison of related homochiral austalides difficult. All compounds were evaluated for their cytotoxic activity against murine cancer cell line L5178Y by using the MTT method. Compounds 8 and 11 exhibited moderate to pronounced cytotoxicity, with IC50 values of 39.4 and 0.2 μM, respectively, whereas the remaining investigated compounds showed either weak or no activity in this assay.

An efficient one-pot synthesis of hydroxynaphthyl-substitutedglycine derivatives from 2- or 1-naphthol, glyoxylic acid, and benzylcarbamate via a modified Mannich reaction is described. The enantiomerswere successfully separated on analytical and semipreparative HPLCcolumns. Their absolute configurations were determined by CD analysissupported by TDDFT CD calculations.

Six unusual xanthone-chromanone dimers, versixanthones A-F (1-6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1-6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone-chromanone dimers and supported the assignments of their absolute configurations. Compounds 1-6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 μM. Compound 5 showed further inhibitory activity against topoisomerase I.

One new resorcylic acid derivative (IV), and five new loop-opened resorcylic acid-related congeners, including brocapyrone A (III), and brocaketones A-D (structure examples (I) and (II)) are isolated together with three known compounds.

Dihydroaltersolanol B (Ia), dihydroaltersolanol C (Ib), acetylalterporriol D (II) and the atropisomer acetylalterporriol E are isolated from the title fungus.

The alkaloid varioexpine A (I) is isolated from the marine fungus Paecilomyces variotii and its structure is characterized by NMR spectroscopy and X-ray analysis.

The three new brocaeloids (I)-(III) are isolated from the cultures of penicillium brocae MA-192.

Two new pyridine-containing limonoids, xylogranatopyridines A (I) and B (II) and their formal precursor, prexylogranatopyridine (III), are isolated and evaluated for their protein tyrosine phosphatase 1B (PTP1B) activity.

Two new sarsolenane diterpenes, dihydrosarsolenone (2), methyl dihydrosarsolenoneate (3), and two new capnosane diterpenes, sarsolilides B (5) and C (6), were isolated together with the known analogue, sarsolilide A (4), from the Hainan soft coral Sarcophyton trocheliophorum Marenzeller. Their structures were elucidated by detailed spectroscopic analysis and by comparison with reported data, leading to a structure revision of sarsolenone (1). The absolute configurations of 2 and 5 were determined by TDDFT ECD calculations, and they could be used as ECD reference compounds in the determination of the absolute configuration of their related derivatives. Compounds 4 and 5 exhibited inhibitory activity in vitro against protein tyrosine phosphatases 1B (PTP1B), representing the first report of PTP1B inhibitory activity for capnosane diterpenes.

The dimeric anthracene derivative torrubiellin B ( 1 ) was isolated from the endophytic fungus Acremonium sp. that had been obtained from leaves of the Mangrove plant Sonneratia caseolaris . The absolute configuration of 1 was established as (5′ R ,10′ S ,10a′ R ) for the first time on the basis of its electronic circular dichroism (ECD) spectra aided with TDDFT-ECD calculations. Torrubiellin B ( 1 ) exhibited strong anti-tumor activity when tested in vitro against several solid cancer cell lines including cells that are resistant against the widely used cytostatic drug cisplatin. The IC 50 values of 1 against cisplatin sensitive and cisplatin resistant cells were in the range of 0.2–2.6 μM depending on cell line investigated.

The absolute configuration of the resolved axially chiral pyridine- N -oxide derivative, (±)- trans -2,6-di- ortho -tolyl-3,4,5-trimethylpyridine- N -oxide, has been determined by VCD and ECD analyses supported by TD-DFT calculations carried out at different levels of theory. DFT calculations confirmed that in spite of the two biaryl axes, the compound is conformationally less flexible and the major conformer is stabilized by two weak hydrogen bonds formed between the hydrogen of the methyl group of the tolyl moieties and the nitroxide oxygen. The experimental VCD spectra of this compound and the previously studied (±)-2,6-di-sec-butyl-4-methylpyridine-N-oxide with two stereogenic centers were compared in the frequency range 1200–1300 cm −1 . A (+,−,+)/(−,+,−) pattern of bands was observed in both cases. By replacing the sec -butyl moieties with tolyl ones, the VCD peaks shifted toward higher frequencies and the intensities were increased.

The marine-derived fungus Penicillium sp. (strain IO1) isolated from the Mediterranean sponge Ircinia oros yielded a new fusarielin analogue ( 1 ) together with the known compounds griseofulvin ( 4 ) and dechlorogriseofulvin ( 5 ). The structure of 1 was unambiguously elucidated by comprehensive spectroscopic analysis (1D and 2D NMR, and mass spectrometry) as well as by comparison with the literature, while the absolute configuration of 1 was determined on the basis of TDDFT ECD calculations. A further Penicillium sp. (strain IO2) that was isolated from the same sponge I. oros yielded the known compounds dehydrocurvularin ( 6 ), curvularin ( 7 ), and trichodimerol ( 8 ). Co-cultivation of both Penicillium strains (IO1 and IO2) was found to induce the accumulation of the known norlichexanthone ( 2 ) and monocerin ( 3 ) that were not detected in either of the two axenic fungal controls. Compounds 3 and 6 showed pronounced cytotoxicity against the murine lymphoma (L5178Y) cell line with IC 50 values of 8.4 and 4.7 μM, respectively.

Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silico conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity.

Four new tetrahydroanthraquinone derivatives, namely, dihydroaltersolanol B (1), dihydroaltersolanol C (2), and the atropisomers acetylalterporriol D (3) and acetylalterporriol E (4), were obtained from the endophytic fungus Stemphylium globuliferum, which was isolated from Juncus acutus growing in Egypt. The structures of the new compounds were unambiguously elucidated on the basis of one- and two-dimensional NMR spectroscopy, as well as by high-resolution mass spectrometry and electronic circular dichroism (ECD) spectroscopy. In addition, seven known anthraquinone derivatives 5–11 were isolated and identified on the basis of their spectral characteristics and by comparison with literature data. Compounds 2, 4–7, 9, and 11 showed strong cytotoxicity against the murine lymphoma cell line L5178Y with IC50 values ranging from 1.25 to 10.4 μM. Compounds 1–4 were also tested for their antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Only 2 exhibited moderate growth inhibition against S. aureus with a minimum inhibitory concentration (MIC) of 49.7 μM.

The endophytic fungus Xylaria sp. was isolated from healthy leaves of Curcuma xanthorrhiza, collected on the island of Timor, Indonesia. Two new compounds (1 and 2), together with the known resacetophenone (3), were isolated and their structures were elucidated on the basis of comprehensive NMR and mass spectral analyses. The enantiomers of rac-1 were separated by chiral HPLC and their HPLC-ECD spectra were recorded to determine the absolute configuration on the basis of TDDFT-ECD calculations. The (3R,3aR, 9aR) absolute configuration of the optically active 2 was established by comparing the experimental solution ECD spectrum with the TDDFT ones computed for the gas phase and solution (PCM solvent model) conformers.

The [4+2] cycloaddition remains one of the most intriguing transformations in synthetic and natural products chemistry. In nature, however, there are remarkably few enzymes known to have this activity. We herein report an unprecedented enzymatic [4+2] cyclization cascade that has a central role in the biosynthesis of pyrroindomycins, which are pentacyclic spirotetramate natural products. Beginning with a linear intermediate that contains two pairs of 1,3-diene and alkene groups, the dedicated cyclases PyrE3 and PyrI4 act in tandem to catalyze the formation of two cyclohexene rings in the dialkyldecalin system and the tetramate spiro-conjugate of the molecules. The two cyclizations are completely enzyme dependent and proceed in a regio- and stereoselective manner to establish the enantiomerically pure pentacyclic core. Analysis of a related spirotetronate pathway confirms that homologs are functionally exchangeable, establishing the generality of these findings and explaining how nature creates diverse active molecules with similar rigid scaffolds.

Pierre Chandon writes: In 2003, what can we learn from what happened to Clamoxyl in France in 1996? The Clamoxyl story shows that pharmaceutical brands can have considerable equity and can thus put up a successful defence against generics. This is a lesson that many pharmaceutical companies should ponder, given how little respect they generally have for their brands. For example, we too often see newly merged corporations happily forfeiting esteemed old brands in favour of new acronyms with zero awareness and weak image. A market-savvy company would not give up that easily on these fantastic brands and on the value that they have, inside and outside the company. Similarly, too few pharmaceutical companies know how to leverage the power of their brands through careful brand extensions or coherent brand architecture (the relationship between the corporate brand and all the product brands). Finally, pharmaceutical companies are still learning how to brand the total customer experience, that is, not just the product, but the name, the packaging, the delivery system, and the preand post-consumption information search. Another lesson from the Clamoxyl story is the importance of replacing a narrow problem definition (price competition from generics) in favour of a real understanding of the goals and constraints of the key stakeholder (in this case, the French social security system’s goal of reducing the growth in antibiotic reimbursements). This lesson still holds today, although the specific strategy implemented in 1996 is no longer valid. Consider Augmentin, whose patent expired in France in 2002. The new law introduced in 1999 shifted a significant amount of power from the doctor to the pharmacists, who are now allowed to change a prescription to any cheaper generic. Most generics offer higher unit margins and therefore Augmentin would not gain if they were to reduce the price. Doctors would be more likely to prescribe it but pharmacists would continue to sell generics instead (and would be irritated at the lower margins for Augmentin). GSK therefore decided to license Augmentin to three generic makers six months before the end of the patent protection period. In exchange for royalties, these generics producers obtained manufacturing know-how and, most importantly, a head start deterring entry of other generic makers and hence reducing price competition.

Recent trends of patent enforcement in the pharmaceutical industry are discussed with particular reference to chemical process patents, formulation patents, patented salts and derivatives, polymorph patents, second indication inventions, metabolite patents and dosage regimen patents. The basic principles of patent rights are summarised and practical recommendations are disclosed on the patentability, enforceability and invalidation of the patent types discussed above. Some tactical advice is presented for generics companies on how to endeavour to avoid patent conflicts and what to do in case of an infringement suit. The importance of patenting the R&D results of generic companies, in terms of the creation of chemical and biological generic products, is emphasised.

The oxidation of enol acetate of flavone (I) results in the formation of two products whereas, the ratio of flavone (II) and isoflavone (III) strongly depends on the reaction conditions used.

A new 3H-oxepine-containing alkaloid, varioxepine A (1), characterized by a structurally unprecedented condensed 3,6,8-trioxabicyclo[3.2.1]octane motif, was isolated from the marine algal-derived endophytic fungus Paecilomyces variotii. Due to the low proton/carbon ratio, the unambiguous assignment of the planar structure and relative configuration was precluded by NMR experiments and solved by single crystal X-ray analysis. The absolute configuration was established by DFT conformational analysis and TDDFT-ECD calculations. Compound 1 inhibited plant pathogenic fungus Fusarium graminearum.

The isolation, structure elucidation and biosynthetic pathway of the title compound are described.

Eleganketal A (1), a naturally occurring aromatic polyketide possessing a rare highly oxygenated spiro[isobenzofuran-1,3'-isochroman] ring system, was isolated from the fungus Spicaria elegans KLA03 by culturing it in a modified mannitol-based medium. The structure of 1 including the absolute configuration was determined by combining spectroscopic analysis, synthesis of the racemic permethylated analogue, chiral-phase HPLC separation, and TDDFT-ECD analysis.

The title compound (I) exhibits substantial antibacterial activity against a broad spectrum of Gram-positive bacterial species (e.g. staphylococci, streptococci, enterococci, B.

Condensed O,N-heterocycles containing tetrahydro-1,4-benzoxazepine and tetrahydroquinoline moieties were prepared by a regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction of a 4-aryl-2-phenyl-1,4-benzoxazepine derivative obtained from flavanone. The relative configuration of products were determined by the correlation of 3JH,H coupling data with the geometry of major conformers accessed by DFT conformational analysis. Separated enantiomers of the products were characterized by HPLC-ECD data, which allowed their configurational assignment on the basis of TDDFT-ECD calculation of the solution conformers. Two compounds showed neuroprotective activities against hydrogen peroxide (H2O2) or β-amyloid25–35 (Aβ25–35)-induced cellular injuries in human neuroblastoma SH-SY5Y cells in the range of those of positive controls.

A novel pyrrolizidine alkaloid, penibruguieramine A (1), characterized by an unprecedented 1-alkenyl-2- methyl-8-hydroxymethylpyrrolizidin-3-one skeleton, was isolated from the endophytic fungus Penicillium sp. GD6, associated with the Chinese mangrove Bruguiera gymnorrhiza. The absolute configuration of penibruguieramine A (1) was established by TDDFT ECD calculations of the vacuum and solution conformers, exploiting the transitions of the lactam chromophore. A plausible pathway for its biosynthesis has been proposed.

Two new pyridine-containing limonoids, xylogranatopyridines A and B (1 and 2) and their formal precursor, prexylogranatopyridine (3) were isolated from the twigs and leaves of the Chinese mangrove, Xylocarpus granatum. Xylogranatopyridine B (2) possesses an unprecedented rearranged B-ring together with a seco-ring A, supporting the biogenetic connection of 1–2 with 3. The chemical structures were elucidated by means of detailed spectroscopic analysis and X-ray single-crystal diffraction. The absolute configurations were assigned using electronic solid-state circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) ECD calculations and X-ray analysis. Xylogranatopyridine A (1) exhibited a significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 22.9 μM. This is the first report of PTP1B inhibitory activity of limonoids.

Neosartorin ( 1 ) was isolated from the endophytic fungus Aspergillus fumigatiaffinis . The absolute configuration of 1 , including both axial and central chirality elements, was established as (a R ,5 S ,10 R ,5′ S ,6′ S ,10′ R ) for the first time on the basis of its electronic circular dichroism (ECD) spectra aided with TDDFT–ECD calculations. Neosartorin ( 1 ) exhibited substantial antibacterial activity against a broad spectrum of Gram-positive bacterial species including staphylococci, streptococci, enterococci, and Bacillus subtilis with minimal inhibitory concentrations in the range of 4–32 μg/mL. When the toxicity of 1 against eukaryotic cells was measured using a panel of different cancer cell lines such as HELA and BALB/3T3, the average IC 50 values exceeded 32 μg/mL.

A chiral tetralin norsesquiterpenoid, ligukangtinol, was isolated from the plant Ligularia kangtingensis. Its planar structure was determined by extensive analysis of spectroscopic data (MS, IR, and NMR), and (1S,3R) absolute configuration of the tetralin ring was established by TDDFT-ECD calculations of the solution conformers. Conformational analysis and ECD calculations proved that the semiempirical helicity rules of 6-hydroxytetralins correlating the (1)L(b) Cotton effect and P/M helicity of the fused carbocyclic ring correctly predicts the absolute configuration and thus can be used for the configurational assignment of related substituted tetralin derivatives.

Four tetrahydroxanthone dimers (1-4) and four biogenetically related monomers (5-8), including the new derivatives 4-6, were isolated from the endophyte Phomopsis longicolla. The absolute configurations of 2-4 were established for the first time by TDDFT electronic circular dichroism calculations, and that of phomoxanthone A (1) was revised by X-ray crystallography. Phomoxanthone A (1) showed the strongest pro-apoptotic activity when tested against a panel of human cancer cell lines, including cisplatin-resistant cells, whereas it was up to 100-fold less active against healthy blood cells. It was also the most potent activator of murine T lymphocytes, NK cells, and macrophages, suggesting an activation of the immune system in parallel to its pro-apoptotic activity. This dual effect in combating cancer cells could help in fighting resistance during chemotherapy. Preliminary structure-activity studies of isolated compounds and derivatives obtained by semisynthesis (9a-11) hinted at the location of the biaryl axis and the presence of acetyl groups as important structural elements for the biological activity of the studied tetrahydroxanthones.

An unprecedented complementarity of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectroscopic techniques is demonstrated by showing that each technique reveals the structure of a different molecular segment. Using a flexible molecule of biological significance we show that the synergetic use of ECD and VCD yields more complete structural characterization as it provides improved and more reliable conformer resolution.

isolation, structure determination and cytotoxicity of 13 new 12-membered macrolides, dendrodolides A—M

Dendrodolides A-M (1-13), 13 new 12-membered macrolides, were isolated from Dendrodochium sp., a fungus associated with the sea cucumber Holothuria nobilis Selenka, which was collected from the South China Sea. The structures of the dendrodolides were elucidated by means of detailed spectroscopic analysis and X-ray single-crystal diffraction. The absolute configurations were assigned using the modified Mosher method, exciton-coupled circular dichroism (ECCD), electronic solution and solid-state circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) ECD calculations, and X-ray analysis. A detailed conformational analysis of the 13 derivatives indicated that the conformation of the flexible macrolide ring plays a decisive role in their chiroptical properties. Thus, it is highly recommended to apply advanced levels of theory and to avoid simple comparison of ECD spectra to determine the absolute configurations of these derivatives. In an in vitro bioassay, compounds 1-5, 7-9, 11, and 12 exhibited different levels of growth inhibitory activity against SMMC-7721 and HCT116 cells. This is the first report of 12-membered macrolides from the fungus of the genus Dendrodochium . The coisolation of four pairs of epimers is extremely interesting and indicates the complexity of β-ketoreductase stereospecificity in the biosynthesis of enigmatic iterative fungal polyketides.

The photophysical properties of a new naphthalene based fluorophore, namely the 1-amino-5-isocyanonaphthalene (ICAN) investigated by steady-state and time-resolved fluorescence methods are reported. The molecule showed positive solvatochromic properties, that is a more than Δ v ¯ = 4800 cm − 1 red-shift of the emission maximum was observed (from 409 nm in hexane to 513 nm in water). The fluorescence quantum efficiency was found to decrease with increasing solvent polarity, from an excellent ΦF = 0.95 in 1,4-dioxane to ΦF = 0.04 in water. The Kamlet–Taft theory turned out to give the most appropriate description of the solvatochromic properties of the ICAN in various solvents including both protic and non-protic solvents. By carrying out experiments in cyclohexane/tetrahydrofuran binary mixtures of different compositions, evidence was found for the preferential solvation of ICAN. Based on laser light flash photometry measurements the radiative decay rate of ICAN was determined for six different solvents of largely different polarity. The decay rates show only minor solvent dependence and the life-times of the excited states are in the order of 10 ns which are in good agreement with the calculated values. The practical applicability of ICAN was demonstrated by determining the critical micelle concentration of sodium laurylsulfate in water.

Effusin A (1), a spirobicyclic N,O-acetal derivative with an unprecedented 3',3a',5',6'-tetrahydrospiro[piperazine-2,2'-pyrano[2,3,4-de]chromene] ring system, and a spiro-polyketide-diketopiperazine hybrid dihydrocryptoechinulin D (2) were isolated from a mangrove rhizosphere soil derived fungus, Aspergillus effuses H1-1. Their structures were determined by detailed spectroscopic analysis. Effusin A (1) and dihydrocryptoechinulin D (2) occurred as racemates, the enantiomers of which were separated and characterized by online HPLC-ECD analysis and their absolute configurations were determined by the solution TDDFT ECD calculation approach. The cytotoxic effects of 1 and 2 were preliminarily evaluated and 2 showed potent activity on P388 cells with an IC(50) value of 1.83 μM. The target of racemic 2 was also investigated and the (12R,28S,31S)-2 enantiomer showed selectivity against topoisomerase I.

Three new polyketides ((-)-1, (+)-1, and 2) were isolated from the EtOAc extract of the fungus Embellisia eureka, an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae). The structures of these new compounds were determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of (-)-1, (+)-1, and 2 were determined by TDDFT ECD calculations of solution conformers, online HPLC-ECD analysis, and the modified Mosher method.

The aflatoxin mycotoxins are particularly hazardous to health when present in food. Therefore, from an analytical point of view, knowledge of their mass spectrometric properties is essential. The aim of the present study was to describe the collision-induced dissociation behavior of the four most common aflatoxins: B1, B2, G1 and G2.Protonated aflatoxins were produced using atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) combined with high-performance liquid chromatography (HPLC). For the tandem mass spectrometry (MS/MS) experiments nitrogen was used as the collision gas and the collision energies were varied in the range of 9-44 eV (in the laboratory frame).The major APCI-MS/MS fragmentations of protonated aflatoxins occurred at 30 eV collision energy. The main fragmentation channels were found to be the losses of a series of carbon monoxide molecules and loss of a methyl radical, leading to the formation of radical-type product ions. In addition, if the aflatoxin molecule contained an ether- or lactone-oxygen atom linked to a saturated carbon atom, loss of a water molecule was observed from the [M + H](+) ion, especially in the case of aflatoxins G1 and G2.A relatively small modification in the structure of aflatoxins dramatically altered the fragmentation pathways and this was particularly true for aflatoxins B1 and B2. Due to the presence of a C = C double bond connected to the ether group in aflatoxin B1 no elimination of water was observed but, instead, formation of radical-type product ions occurred. Fragmentation of protonated aflatoxin B1 yielded the most abundant radical-type cations.

Indotertine A (1), a hybrid isoprenoid with a condensed pentacyclic skeleton, together with two related hybrid isoprenoids, drimentines F (2) and G (3), were isolated from a reeds rhizosphere soil derived actinomycete Streptomyces sp. CHQ-64. Their structures including absolute configurations were elucidated by spectroscopic methods, X-ray single crystal diffraction analysis, and TDDFT ECD calculations. Drimentines G (3) showed strong cytotoxicity against human cancer cells lines with IC(50)'s down to 1.01 μM, while 1 and 2 showed no significant activity.

Four known hydroxyanthraquinones (1-4) together with four new derivatives having a tetralone moiety, namely coniothyrinones A-D (5-8), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations of coniothyrinones A (5), B (6), and D (8) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C (7) as well. Coniothyrinones A (5), B (6), and D (8) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives. This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp. These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium.

Chemical investigation of the ethyl acetate extract of Corynespora cassiicola, isolated from leaf tissues of the Chinese mangrove medicinal plant Laguncularia racemosa, yielded four new secondary metabolites, including three decalactones, xestodecalactones D–F (1–3) as well as corynesidone C (4), in addition to four known compounds. The structures of the new compounds were determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. Absolute configurations of the optically active compounds 1–3 were determined by TDDFT ECD calculations of their solution conformers, proving that they belong to the (11S) series of xestodecalactones, opposite to the (11R) configuration of the known xestodecalactones A–C. All compounds were tested against a panel of human protein kinases. Among the isolated compounds, two inhibited several kinases such as IGF1-R and VEGF-R2 with IC50 values mostly in the low micromolar range.

Four new indolo-sesquiterpenes dixiamycins A (1) and B (2), oxiamycin (3), and chloroxiamycin (4) were isolated from a marine-derived Actinomycete and characterized, together with the known compound xiamycin A (5). Dixiamycins A (1) and B (2) are the first examples of atropisomerism of naturally occurring N-N-coupled atropo-diastereomers, with a dimeric indolo-sesquiterpene skeleton and a stereogenic N-N axis between sp3-hybridized nitrogen atoms. Solution TDDFT ECD calculations were utilized to ascertain the axial chirality of 1 and 2, and rotational barriers and transitions states of the inversion were calculated. Oxiamycin (3) contains a seven-membered 2,3,4,5-tetrahydrooxepine ring. The two dimeric compounds 1 and 2 showed better antibacterial activities than the monomers 35.

NMDA receptors form a major subdivision of the ionotropic glutamate receptor family that mediates excitatory synaptic transmission in the brain. Series of 1-substituted 1,2-dihydroimidazo[5,1- b ]quinazolinediones were synthesized and found to have potent nanomolar activity at the glycine site of the NMDA receptor. Imidazoquinazolinediones were prepared by cyclocondensation of 4-oxo-quinazoline-2-carboxamide with aldehydes and orthoesters with good yields. The formed enantiomers were separated by chiral HPLC. The absolute configuration of pure enantiomers is elucidated by combined CD/Quantumchemical time-dependent DFT calculation method (TDDFT).

Palmarumycins BG1-BG7 (1-7), seven new compounds related to palmarumycins, were isolated from the aerial parts of Bruguiera gymnorrhiza as well as a new preussomerin derivative BG1 (8). The structures of these compounds were determined mainly by the analysis of their NMR and MS data, and their relative configurations were assigned on the basis of their (3)J(H,H) coupling constants. Compounds 4 and 7 have a sulfate group that is unprecedented among members of spirodioxynaphthalene-type natural products. The absolute configurations of 1-8 were determined by TDDFT CD calculations of the solution conformers. Compound 5 displayed inhibitory activity against HL 60 and MCF-7 cell lines.

The potential energy surface for dioxolane ring-opening and hydride donation for the title compound has been mapped. The transition state (TS) was determined at various levels of theories and it has been proven by intrinsic reaction coordinate calculations that it connects the reactant to the product. The breaking of the O3–Cacetal bond and formation of the new H–C bond seems to occur in one (rate limiting) elementary step, which is, however, rather asynchronous.

Two novel chlorinated sorbicillinoids named chloctanspirones A ( 1 ) and B ( 2 ), possessing an unprecedented bicyclo[2.2.2]octane-2-spiro cyclohexane skeleton, together with their quasi-precursors terrestrols K ( 3 ) and L ( 4 ), two additional new chlorinated compounds, were isolated from a marine sediment derived fungus Penicillium terrestre . Their structures including absolute stereochemistries were elucidated by analysis of NMR, MS data, and TDDFT CD calculations. The cytotoxic effects of 1 – 4 were preliminarily evaluated in HL-60 and A-549 cells. Compound 1 was active against both HL-60 and A-549 cells with IC 50 s 9.2 and 39.7 μM, respectively, while 2 showed weaker activity only against HL-60 cells (IC 50 37.8 μM).