Selective enhancement of (6-4) photoproduct formation in dithymine dinucleotides driven by specific sugar puckering.

Four dinucleotide analogs of thymidylyl(3'-5')thymidine (TpT) have been designed and synthesized with a view to increase the selectivity, with respect to CPD, of efficient UV-induced (6-4) photoproduct formation. The deoxyribose residues of these analogs have been modified to increase north and south conformer populations at 5'- and 3'-ends, respectively. Dinucleotides whose 5'-end north population exceeds ca. 60% and whose 3'-end population is almost completely south display a three-fold selective enhancement in (6-4) adduct production when exposed to UV radiation, compared to TpT. These experimental results undoubtedly provide robust foundations for studying the singular ground-state proreactive species involved in the (6-4) photoproduct formation mechanism.

Facile green in situ hemisynthesis of new chiral chromeno-pyrimidine derivatives: antibacterial, antioxidant activities and molecular docking study.

A hemisynthesis 'in situ' reaction of (thio)barbituric acids with an α,ß-unsaturated aldehyde using perillaldehyde from Ammodaucus leucotrichus essential oil, afforded chromeno-pyrimidine derivatives B-1 and B-2. The reaction was carried out in water and water/ethanol medium without a catalyst. The obtained pyrimidines were identified by their spectral 1H,13C, Dept-135, HMBC, HSQC, COSY, and NOESY 2D. The antioxidant activity of both compounds was evaluated using different in vitro methods (DPPH, ABTS, and CUPRAC). The hemisynthesized molecules exhibited a bacteriostatic effect against ten tested gram (+) and gram (-) strains. According to the molecular docking analysis, B-1 showed lower binding energies compared to B-2 against (PDB: 1HD2) and (PDB: 1KZN) targets, which is in agreement with the ABTS and E. Coli assays. Furthermore, a probable promising anti-HIV activity was noticed against reverse transcriptase (PDB: 2RKI), a key enzyme for HIV replication. The ADME properties calculations showed no Lipinski's rule violation for both compounds.

A new triterpene saponin and known compounds from the polar extract of Salvia argentea L. and evaluation of their antioxidant activity.

A new triterpene saponin, 2, 3, 21, 23-tetrahydroxyolean-12-en-28-oic-acid-28-O-ß-D- glucosyl-(2''→1')-ß-D-glucoside (1), was isolated from the n-butanol extract of dried aerial parts of Salvia argentea L. (Lamiaceae) in addition to two known flavonoids, apigenin 7-O-ß-D-glucoside (2), threo-guaiacylglycerol 3-O-[6-O-p-hydroxybenzoyl]-ß-D-glucoside (3), luteolin 7-O-ß-D-glucoside (4), verbascoside (5) and rosmarinic acid (6). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D-, 2D-NMR and HR-ESI-MS techniques and by comparing their NMR data with those reported in the literature. Compound 6 exhibited the highest antioxidant activity in DPPH assay (IC50<3.00 µg/mL) which was better than the standards BHA, BHT, Trolox and ascorbic acid.

Transcriptomic analysis of lignocellulose degradation by Streptomyces coelicolor A3(2) and elicitation of secondary metabolites production.

Streptomyces coelicolor A3(2) is considered as the model strain among the Streptomyces and has the capacity to produce several natural molecules. Our hypothesis was that cultivation of the strain onto a complex carbon source such as wheat bran (WB) would induce the production of various secondary metabolites due to the presence of complex polysaccharides. A multiapproach has been performed in order to investigate: (1) whether that strain could degrade lignocellulose; (2) which enzymatic and metabolic pathways secondary were over-expressed when grown on WB. The transcriptomic approach showed the expression of several CAZymes significantly expressed when grown on WB such as endoglucanases (encoding for GH74, GH5_8, and GH12) and xylanases (GH11 and CE4 encoding for respectively endo-1,4-beta-xylanase and an acetyl-xylan esterase). Enzymatic activities showed an expression of xylanase (115.3 ± 32.2 mUI/ml) and laccase-peroxidase (101.5 ± 10.9 mUI/ml) during WB degradation by S. coelicolor A3(2). Metabolomics showed that the production of secondary metabolites differed between growth on either glucose or WB as carbon source, which may be correlated to the complexity of carbon compounds within WB, which are similar to the ones encountered in soils and should represent more the in situ carbon conditions which Streptomyces might face off. This opens opportunities for the bioproduction of molecules of interest from WB.

Co-elicitation of lignocelluloytic enzymatic activities and metabolites production in an Aspergillus-Streptomyces co-culture during lignocellulose fractionation.

Lignocellulose, the most abundant biomass on Earth, is a complex recalcitrant material mainly composed of three fractions: cellulose, hemicelluloses and lignins. In nature, lignocellulose is efficiently degraded for carbon recycling. Lignocellulose degradation involves numerous microorganisms and their secreted enzymes that act in synergy. Even they are efficient, the natural processes for lignocellulose degradation are slow (weeks to months). In this study, the objective was to study the synergism of some microorganisms to achieve efficient and rapid lignocellulose degradation. Wheat bran, an abundant co-product from milling industry, was selected as lignocellulosic biomass. Mono-cultures and co-cultures involving one A.niger strain fungi never sequenced before (DSM 1957) and either one of three different Streptomyces strains were tested in order to investigate the potentiality for efficient lignocellulose degradability. Comparative genomics of the strain Aspergillus niger DSM 1957 revealed that it harboured the maximum of AA, CBM, CE and GH among its closest relative strains. The different co-cultures set-up enriched the metabolic diversity and the lignocellulolytic CAZyme content. Depending on the co-cultures, an over-expression of some enzymatic activities (xylanase, glucosidase, arabinosidase) was observed in the co-cultures compared to the mono-cultures suggesting a specific microbial cross-talk depending on the microbial partner. Moreover, metabolomics for each mono and co-culture was performed and revealed an elicitation of the production of secondary metabolites and the activation of silent biosynthetic cluster genes depending on the microbial co-culture. This opens opportunities for the bioproduction of molecules of interest from wheat bran.

SN- and NS-puckered sugar conformers are precursors of the (6-4) photoproduct in thymine dinucleotide.

Some amount of furanose in a southern conformation, possibly in both, but certainly in one of the two adjacent nucleotides of a dipyrimidine site, is necessary for (6-4) photoproduct formation in oligonucleotides. To explore the necessity, role, and most favorable location of each South sugar conformer in the formation of the (6-4) adduct in the thymine dinucleotide TpT, the photochemical behavior of two synthetic analogues, in which the South sugar conformation is prohibited for one of their two sugars, has been examined. Herein, we experimentally demonstrate that the presence of one sugar presenting some amount of South puckering, at any of the extremities, is sufficient to trigger (6-4) adduct formation. Nonetheless, the photochemical behavior of the dinucleotide with a South-puckered conformation at the 5'-end, mimics more closely that of TpT. In addition, using the 5' North 3' South-dilocked dinucleotide, we demonstrate that the flexibility of the South pucker at the 3'-end has little influence on the (6-4) adduct formation.

Tuning the Regioselective Functionalization of Trifluoromethylated Dienes via Lanthanum-Mediated Single C-F Bond Activation.

The development of new fluorine-containing building blocks and their efficient synthetic access is currently a challenging research field. Herein, the highly regio- and stereoselective addition of a large range of aldehydes onto trifluoromethylated benzofulvenes was achieved using a simple La/I2 /DIBAL-Cl system via a selective C-F bond activation process. This versatile methodology provided homodienyl alcohols bearing a terminal CF2 -alkene with potential further applications, as shown by the dehydration to the first benzofulvenes carrying a difluorovinyl group. In addition, for certain electron-poor aldehydes, unprecedented ipso substitution of the CF3 group in a diene was observed, which, according to DFT studies, is related to the presence of the large, Lewis-acidic lanthanum metal.

Pyrroloquinolone A, a new alkaloid and other phytochemicals from Atractylis cancellata L. with antioxidant and anticholinesterase activities.

A new alkaloid pyrroloquinolone A (1), along with fifteen known compounds 2-16 were isolated from the petroleum ether, EtOAc and n-BuOH extracts of the whole plant Atractylis cancellata L. Their structures were elucidated on the basis of extensive spectroscopic analysis including 1D- and 2D-NMR and HR-ESI-MS techniques. This is the first report of alkaloids in the genus Atractylis. Some of the isolated compounds and extracts were evaluated for their antioxidant potential (scavenging activity of DPPH and ABTS radicals, and reducing Fe+3 and Cu+2 power assays) and acetylcholinesterase and butyrylcholinesterase inhibitory activities. Compounds 8 and 11 showed good antioxidant capacity compared to ascorbic acid, BHA, and BHT used as standards, whereas compounds 1 and 2 exhibited good anticholinesterase activities compared to galantamine used as standard.

Glucosinolates of Lepidium graminifolium L. (Brassicaceae) from Croatia.

The glucosinolate (GSL) profiles (inflorescence, stem, root, and fruit) of the wild-growing plant Lepidium graminifolium L. (Brassicaceae) from Croatia was established by LC-MS analysis. During this investigation, we confirmed the presence of benzyl- (1), 3-methoxybenzyl- (2), 4-hydroxybenzyl- (4), 4-methoxyindol-3-ylmethyl- (7) GSLs and reported for the first time in the plant the presence of (2 R)-hydroxybut-3-enyl- (11), (2S)-hydroxybut-3-enyl- (12), but-3-enyl- (13), and 2-phenylethyl- (14) GSLs. Finally, 3-hydroxybenzyl GSL (3) was isolated for the first time from L. graminifolium inflorescence and characterised by spectroscopic data interpretation.

Semipapposides A-M, triterpenoid bidesmosides saponins from the roots of Scabiosa semipapposa.

Phytochemical investigations of the roots of Scabiosa semipapposa Salzem ex D.C. have led to the isolation of 12 undescribed triterpenoid saponins named semipapposides A-L, one undescribed saponin semipapposide M obtained as an inseparable mixture, together with three known oleanolic acid glycosides. Their structures were elucidated by analysis of 1D and 2D-NMR (1H-1H COSY, TOCSY, HSQC-TOCSY, HSQC, ROESY or NOESY, and HMBC) spectroscopic data and mass spectrometry (HR-ESI-MS), and by comparison with those of related metabolites. All saponins possess a partial sequence rhamnopyranosyl-(1 â†’ 2)-xylopyranosyl or rhamnopyranosyl-(1 â†’ 2)-arabinopyranosyl- at C-3 of the aglycon and a gentiobiose unit at C-28. These results represent a contribution to the knowledge of the saponins of Scabiosa species and their chemotaxonomy.

Triterpene saponins from Silene gallica collected in North-Eastern Algeria.

Eleven previously undescribed triterpene saponins, named silenegallisaponin A-K (1-11), were isolated from the aerial parts of Silene gallica L. Their structures were elucidated by analysis of 1D and 2D-NMR spectroscopic data and mass spectrometry (HR-ESI-MS). The saponins comprised caulophyllogenin, echinocystic acid, or quillaic acid substituted at C-3 by a ß-d-glucuronic acid or ß-d-galactopyranosyl-(1 â†’ 3)-ß-d-glucuronopyranoside and at C-28 by a ß-d-fucopyranose substituted at C-2 by a ß-d-glucose and at C-3 by a ß-d-glucose or a ß-d-quinovose.

Investigation of the glucosinolates in Hesperis matronalis L. and Hesperis laciniata All.: Unveiling 4'-O-ß-d-apiofuranosylglucomatronalin.

The glucosinolate (GSL) profiles of wild-growing plants from the genus Hesperis, i.e. Hesperis laciniata All. (leaf, stem, flower, and root) from Croatia and Hesperis matronalis L. (leaf, stem, flower, seed, and root) from Canada, were established by LC-MS. During this investigation, 5-(methylsulfanyl)pentyl- (3), 6-(methylsulfanyl)hexyl- (4), 6-(methylsulfinyl)hexyl- (6), and 4'-α-l-rhamnopyranosyloxybenzyl- (17) GSLs were identified. In addition, the presence of 7-(methylsulfinyl)heptyl GSL (18), hydroxy-(α-l-rhamnopyranosyloxy)benzyl GSL, and of one d-apiosylated analogue of 17 were suggested. Moreover, one new GSL, 4'-O-ß-d-apiofuranosylglucomatronalin (19) was isolated from H. laciniata (flower, steam and leaf) and characterized by spectroscopic data interpretation. Finally, we report the presence of 3, 4, 6, 19, glucosinalbin (12), and 4-hydroxyglucobrassicin (20) in H. matronalis and hypothesize the presence of glucomatronalin (13) and 3-hydroxy-6-(methylsulfanyl)hexyl GSL (21).

6"'-O-acetylisospinosin, a new C-glycosylflavone and known compounds from the aerial parts of Cladanthus mixtus.

A new C-glycosylflavone, identified as 6"'-O-acetylisospinosin (1), was isolated from the aerial parts of Cladanthus mixtus together with 30 known compounds. The structures of these compounds were established by interpretation of their spectral data, mainly UV, 1D and 2D NMR spectroscopic methods including (1H and 13C NMR, COSY, ROESY, HSQC and HMBC experiments), ESI-MS, and by comparison with the literature data.

New Oleanane-type glycosides and secoiridoid glucoside from Aptandra zenkeri.

Four new saponins, camelliagenin A and B derivatives, and one new secoiridoid glucoside were isolated from the stem bark of Aptandra zenkeri Engl. (Aptandraceae) together with two known secoiridoid glucosides. Their structures were determined based on a combination of 1D- and 2D-NMR experiments techniques and HR-ESI-MS analysis. This is the first report on saponins in genus Aptandra.

The remarkable UV light invulnerability of thymine GNA dinucleotides.

We herein demonstrate the UV resistance of glycol nucleic acid (GNA) dinucleotides. This resistance sustains the hypothesis of GNA as a nucleic acid prebiotic ancestor on early Earth, a time of intense solar UV light. Such photorobustness, due to the absence of intrastrand base stacking, could offer an opportunity for nanodevice development requiring challenging UV conditions.

Comparison of MRI Properties between Multimeric DOTAGA and DO3A Gadolinium-Dendron Conjugates.

The inherent lack of sensitivity of MRI needs the development of new Gd contrast agents in order to extend the application of this technique to cellular imaging. For this purpose, two multimeric MR contrast agents obtained by peptidic coupling between an amido amine dendron and GdDOTAGA chelates (premetalation strategy, G1-4GdDOTAGA) or DO3A derivatives which then were postmetalated (G1-4GdDO3A) have been prepared. By comparison to the monomers, an increase of longitudinal relaxivity has been observed for both structures. Especially for G1-4GdDO3A, a marked increase is observed between 20 and 60 MHz. This structure differs from G1-4GdDOTAGA by an increased rigidity due to the aromatic linker between each chelate and the organic framework. This has the effect of limiting local rotational movements, which has a positive impact on relaxivity.

Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia.

Heisteria parvifolia Sm. is prescribed in traditional medecine against numerous diseases in Côte d'Ivoire. Due to the shortcoming in scientifical knowledge of use of this species, our investigations revealed five undescribed cyclopeptide alkaloids added to one known derivative namely anorldianine. These compounds were elucidated by 1D and 2D-NMR experiments and comparison with literature data, and confirmed by HR-ESI-MS. Cytotoxic activity evaluation of these compounds against the chronic myeloid leukemia (K565) cell line exhibited an antiproliferative activity with cell growth inhibition from 13% to 46%.

Triterpene saponins from the roots of Parkia bicolor A. Chev.

Five undescribed triterpene-type saponins, parkibicolorosides A-E, a cassane-type diterpene, and a known trimethoxy benzene glucoside were isolated from the roots of Parkia bicolor A. Chev. Their structures were elucidated by different spectroscopic methods including 1D- and 2D-NMR experiments as well as HR-ESI-MS analysis. Their cytotoxic activity against the chronic myeloid leukemia (K562) cell line was evaluated. The monosaccharides saponins exhibited a moderate antiproliferative activity with IC50 ranging from 48.49 ±â€¯0.16 to 81.66 ±â€¯0.17 µM.

Aerobic and Ligand-Free Manganese-Catalyzed Homocoupling of Arenes or Aryl Halides via in Situ Formation of Aryllithiums.

Ligand-free manganese-catalyzed homocoupling of arenes or aryl halides can be carried out under aerobic conditions via the in situ formation of the corresponding aryllithiums. A wide range of biaryls and derivatives has been obtained, and a mechanism involving monomeric manganese-oxo complexes has been proposed on the basis of DFT calculations.

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes.

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the possibility of accessing unique fluorine-containing molecules, which are difficult to obtain by other synthetic pathways. Among various metals, which can undergo C-F activation, lanthanides (Ln) are good candidates as they form strong Ln-F bonds. Lanthanide metals are strong reducing agents with a redox potential Ln3+/Ln of approximately -2.3 V, which is comparable to the value of the Mg2+/Mg redox couple. In addition, lanthanide metals display a promising functional group tolerance and their reactivity can vary along the lanthanide series, making them suitable reagents for fine-tuning reaction conditions in organic and organometallic transformations. However, due to their oxophilicity, lanthanides react readily with oxygen and water and therefore require special conditions for storage, handling, preparation, and activation. These factors have limited a more widespread use in organic synthesis. We herein present how dysprosium metal - and by analogy all lanthanide metals - can be freshly prepared under anhydrous conditions using glovebox and Schlenk techniques. The freshly filed metal, in combination with aluminum chloride, initiates the selective C-F activation in trifluoromethylated benzofulvenes. The resulting reaction intermediates react with nitroalkenes to obtain a new family of difluoroalkenes.