application-elemental-lanthanides-selective-c-f-activation

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 ...

Université de Reims Champagne Ardenne

UV irradiation of 5-azido-2'-deoxyuridine in water provides up to seven products. All likely result from a pivotal azirene, formed by the intramolecular rearrangement of the initially formed nitrene, that undergoes nucleophilic addition at its C5 position. This study strongly suggests that only nucleophilic amino acid residues in close proximity are cross-linkable in photolabeling experiments by using the 5-azidouracil photophore.

Unraveling the photochemistry of the 5-azido-2'-deoxyuridine photoaffinity label.

The stereo- and regioselectivity of triplet-sensitised radical reactions of furanone derivatives have been investigated. Furanones 7a,b were excited to the (3)pipi* state by triplet energy transfer from acetone. Intramolecular hydrogen abstraction then occurred such that hydrogen was transferred from the tetrahydropyran to the beta position of the furanone moiety. Radical combination of the tetrahydropyranyl and the oxoallyl radicals led to the final products 8a,b. In the intramolecular reaction, overall, a pyranyl group adds to the alpha position of the furanone. The effect of conformation was first investigated with compounds 9a,b carrying an additional substituent on the tether between the furanone and pyranyl moiety. Further information on the effect of conformation and the relative configuration at the pyranyl anomeric centre and the furanone moiety was obtained from the transformations of the glucose derivatives 12, 14, 17 and 18. Radical abstraction occurred at the anomeric centre and at the 5'-position of the glucosyl moiety. Computational studies of the hydrogen-abstraction step were carried out with model structures. The activation barriers of this step for different stereoisomers and the abstraction at the anomeric centre and at the 6'-position of the tetrahydropyranyl moiety were calculated. The results of this investigation are in accordance with experimental observations. Furthermore, they reveal that the reactivity and regioselectivity are mainly determined in the hydrogen-abstraction step. Intramolecular hydrogen abstraction (almost simultaneous electron and proton transfer) in (3)pipi* excited furanones only takes place under restricted structural conditions in a limited number of conformations that are defined by the relative configuration of the substrates. It is observed that in the biradical intermediate, back-hydrogen transfer occurs leading to the starting compound. In the case of glucose derivatives, this reaction led to epimerisation at the anomeric centre.

Stereoselective triplet-sensitised radical reactions of furanone derivatives.

Hydrolysis of TA photoproduct leads to two derivatives presenting different formation kinetic profiles depending on the oligomer content. The formation efficiency of TA photoproducts in UV-C-irradiated DNA slightly exceeds the formation of the trans,syn cyclobutane pyrimidine dimer at TT sites.

UV-induced TA photoproducts: formation and hydrolysis in double-stranded DNA.

The 2-azido analogue of 2'-deoxyuridine was prepared in three steps from 2'-deoxy-2-thiouridine. The sulfur atom of the 2-thio nucleoside was methylated and then displaced by hydrazine to furnish the corresponding 2-hydrazino derivative. After diazotization, the 2-azido compound that exists as its tetrazolo tautomer was obtained. Upon UV irradiation in aqueous solution, the title compound led to isocytosine.

Synthesis and photochemical behavior of the tetrazolo tautomer of 2-azido-4-pyrimidinone-2'-deoxyriboside.

Our goal in the search for potentially bioactive analogues of KRN 7000 was to design an easy synthetic approach to a library of analogues using a strategy recently developed in our laboratory based on a Nucleophilic addition followed by an Epoxide Opening (the NEO strategy). Through the use of a common pivotal structure, a new C-galactoside ester analogue (23) was synthesized which showed an encouraging T(H)2 biased response during preliminary biological tests.

Use of the NEO strategy (Nucleophilic addition/Epoxide Opening) for the synthesis of a new C-galactoside ester analogue of KRN 7000.

This paper describes the implementation of the pure absorption ALPESTRE processing of 2D homonuclear J-resolved NMR spectra. The method relies on the computation of the missing information at negative evolution times by means of backward linear prediction. The paper also shows that resolution can be improved by application of time-symmetric apodization functions. The resulting spectra clearly display negative peaks at F(2) chemical shifts that correspond to strong coupling artifacts, thus making it possible to identify them as such. The processing scripts are freely available for downloading, use and modification.

High-resolution and high-sensitivity 2D homonuclear J-resolved NMR spectroscopy.

Botrytis cinerea is a fungal plant pathogen of grape berries, leading to economic and quality losses in wine production. The global metabolite changes induced by B. cinerea infection in grape have not been established to date, even though B. cinerea infection is known to cause significant changes in chemicals or metabolites. In order to better understand metabolic mechanisms linked to the infection process and to identify the metabolites associated with B. cinerea infection, (1)H NMR spectroscopy was used in global metabolite profiling and multivariate statistical analysis of berries from healthy and botrytized bunches. Pattern recognition methods, such as principal component analysis, revealed clear metabolic discriminations between healthy and botrytized berries of botrytized bunches and healthy berries of healthy bunches. Significantly high levels of proline, glutamate, arginine, and alanine, which are accumulated upon plant stress, were found in healthy and botrytized berries of botrytized bunches. Moreover, largely degraded phenylpropanoids, flavonoid compounds, and sucrose together with markedly produced glycerol, gluconic acid, and succinate, all being directly associated with B. cinerea growth, were only found in botrytized berries of botrytized bunches. This study reports that B. cinerea infection causes significant metabolic changes in grape berry and highlights that both the metabolic perturbations associated with the plant defence system and those directly derived from fungal pathogen growth should be considered to better understand the interaction between metabolic variation and biotic pathogen stress in plants.

Metabolomics reveals simultaneous influences of plant defence system and fungal growth in Botrytis cinerea-infected Vitis vinifera cv. Chardonnay berries.

Technological advances in the field of biological imaging now allow multi-modal studies of human embryo anatomy. The aim of this study was to assess the high magnetic field μMRI feasibility in the study of small human embryos (less than 21mm crown-rump) as a new tool for the study of human descriptive embryology and to determine better sequence characteristics to obtain higher spatial resolution and higher signal/noise ratio.

Human developmental anatomy: microscopic magnetic resonance imaging (μMRI) of four human embryos (from Carnegie Stage 10 to 20).

The aqueous-ethanolic extract of Tephrosia purpurea seeds is currently exploited in the cosmetic industry as a natural ingredient of skin lotions. The aim of this study was to chemically characterize this ingredient by combining centrifugal partition extraction (CPE) as a fractionation tool with two complementary identification approaches involving dereplication and computer-assisted structure elucidation. Following two rapid fractionations of the crude extract (2 g), seven major compounds namely, caffeic acid, quercetin-3-O-rutinoside, ethyl galactoside, ciceritol, stachyose, saccharose, and citric acid, were unambiguously identified within the CPE-generated simplified mixtures by a recently developed (13)C NMR-based dereplication method. The structures of four additional compounds, patuletin-3-O-rutinoside, kaempferol-3-O-rutinoside, guaiacylglycerol 8-vanillic acid ether, and 2-methyl-2-glucopyranosyloxypropanoic acid, were automatically elucidated by using the Logic for Structure Determination program based on the interpretation of 2D NMR (HSQC, HMBC, and COSY) connectivity data. As more than 80% of the crude extract mass was characterized without need for tedious and labor-intensive multistep purification procedures, the identification tools involved in this work constitute a promising strategy for an efficient and time-saving chemical profiling of natural extracts. 

Exploiting the Complementarity between Dereplication and Computer-Assisted Structure Elucidation for the Chemical Profiling of Natural Cosmetic Ingredients: Tephrosia purpurea as a Case Study.

Dirucotide is a synthetic drug candidate for the treatment of multiple sclerosis. This 17-aminoacid peptide was successfully purified by ion exchange centrifugal partition chromatography. The optimized conditions involved the biphasic methyl tert-butyl ether/acetonitrile/n-butanol/water (2:1:2:5, v/v) solvent system in the descending mode, the di(2-ethylhexyl)phosphoric acid cation-exchanger with an exchanger (di(2-ethylhexyl)phosphoric acid)/dirucotide mole ratio of 100 and Ca ions in aqueous solution as displacer. Critical impurities were efficiently eliminated and dirucotide was recovered in high yield and purity (69% and 98%, respectively) and with a productivity of 2.29g per liter of stationary phase per hour.

Purification of dirucotide, a synthetic 17-aminoacid peptide, by ion exchange centrifugal partition chromatography.

Heavy metal on Lewis acid: The combination of lanthanide metals and AlCl has been employed for selective single C-F activation in benzofulvenes comprising an exocyclic CF substituent. Intermediate ϵ,ϵ-difluorinated metal-dienyl species react with a large variety of aldehydes in a highly regio- and diastereoselective fashion to afford 1,1-disubstituted indenes bearing a difluorovinyl group. These new building blocks have been further transformed through a hydrogenation-cyclization process into fluorinated heterocyclic spiro compounds.

Generation of ϵ,ϵ-Difluorinated Metal-Pentadienyl Species through Lanthanide-Mediated C-F Activation.

A new in silico method is introduced for the dereplication of natural metabolite mixtures based on HMBC and HSQC spectra that inform about short-range and long-range H-C correlations occurring in the carbon skeleton of individual chemical entities. Starting from the HMBC spectrum of a metabolite mixture, an algorithm was developed in order to recover individualized HMBC footprints of the mixture constituents. The collected H-C correlations are represented by a network of NMR peaks connected to each other when sharing either a H or C chemical shift value. The network obtained is then divided into clusters using a community detection algorithm, and finally each cluster is tentatively assigned to a molecular structure by means of a NMR chemical shift database containing the theoretical HMBC and HSQC correlation data of a range of natural metabolites. The proof of principle of this method is demonstrated on a model mixture of 3 known natural compounds and then on a real-life bark extract obtained from the common spruce (Picea abies L.).

Article	Year
Unraveling the photochemistry of the 5-azido-2'-deoxyuridine photoaffinity label. The Journal of organic chemistry\| PubMed ID: 19653622	2009
Stereoselective triplet-sensitised radical reactions of furanone derivatives. Chemistry (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 20151440	2010
UV-induced TA photoproducts: formation and hydrolysis in double-stranded DNA. Journal of the American Chemical Society\| PubMed ID: 20662506	2010
Synthesis and photochemical behavior of the tetrazolo tautomer of 2-azido-4-pyrimidinone-2'-deoxyriboside. The Journal of organic chemistry\| PubMed ID: 21306117	2011
Use of the NEO strategy (Nucleophilic addition/Epoxide Opening) for the synthesis of a new C-galactoside ester analogue of KRN 7000. Bioorganic & medicinal chemistry letters\| PubMed ID: 21392982	2011
High-resolution and high-sensitivity 2D homonuclear J-resolved NMR spectroscopy. Magnetic resonance in chemistry : MRC\| PubMed ID: 22271331	2012
Metabolomics reveals simultaneous influences of plant defence system and fungal growth in Botrytis cinerea-infected Vitis vinifera cv. Chardonnay berries. Journal of experimental botany\| PubMed ID: 22945941	2012
Human developmental anatomy: microscopic magnetic resonance imaging (μMRI) of four human embryos (from Carnegie Stage 10 to 20). Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft\| PubMed ID: 25107481	2014
Exploiting the Complementarity between Dereplication and Computer-Assisted Structure Elucidation for the Chemical Profiling of Natural Cosmetic Ingredients: Tephrosia purpurea as a Case Stud... Journal of natural products\| PubMed ID: 26103208	2015
Purification of dirucotide, a synthetic 17-aminoacid peptide, by ion exchange centrifugal partition chromatography. Journal of chromatography. A\| PubMed ID: 28739271	2017
Generation of ϵ,ϵ-Difluorinated Metal-Pentadienyl Species through Lanthanide-Mediated C-F Activation. Chemistry (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 28980352	2017
Reconstruction of HMBC Correlation Networks: A Novel NMR-Based Contribution to Metabolite Mixture Analysis. Journal of chemical information and modeling\| PubMed ID: 29320182	2018

Agathe Martinez

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