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3. Ex vivo potential of a quinoline-derivative nail lacquer as a new alternative for dermatophytic onychomycosis treatment

Author

Marilene Henning Vainstein, Pierre van de Weghe, Denise Diedrich, Simone Jacobus Berlitz, Alexandre Meneghello Fuentefria, Simone Cristina Baggio Gnoatto, Bruna Pippi, Mickael Jean, Diego Defferrari, Gabriella da Rosa Monte Machado, Irene Clemes Külkamp-Guerreiro, William Lopes, Saulo Fernandes de Andrade, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), AlexandreMeneghello Fuentefria , FAPERGS , (Award 16/2551-0000517-6), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
0301 basic medicine, Microbiology (medical), dermatophytes, 030106 microbiology, Nail lacquer, Trichophyton rubrum, Pharmacology, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, medicine, onychomycosis, [CHIM]Chemical Sciences, Inhibitory effect, Ergosterol, biology, Quinoline, General Medicine, biology.organism_classification, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, chemistry, fungicidal effect, Nail (anatomy), ex vivomodel, quinoline derivative, Ex vivo, Derivative (chemistry)
Abstract

Introduction. Onychomycosis infections currently show a significant increase, affecting about 10 % of the world population. Trichophyton rubrum is the main agent responsible for about 80 % of the reported infections. The clinical cure for onychomycosis is extremely difficult and effective new antifungal therapy is needed. Hypothesis/Gap Statement. Ex vivo onychomycosis models using porcine hooves can be an excellent alternative for evaluating the efficacy of new anti-dermatophytic agents in a nail lacquer. Aim. Evaluation of the effectiveness of a nail lacquer containing a quinoline derivative on an ex vivo onychomycosis model using porcine hooves, as well as the proposal of a plausible antifungal mechanism of this derivative against dermatophytic strains. Methodology. The action mechanism of a quinoline derivative was evaluated through the sorbitol protection assay, exogenous ergosterol binding, and the determination of the dose-response curves by time-kill assay. Scanning electron microscopy evaluated the effect of the derivative in the fungal cells. The efficacy of a quinoline-derivative nail lacquer on an ex vivo onychomycosis model using porcine hooves was evaluated as well. Results. The quinoline derivative showed a time-dependent fungicidal effect, demonstrating reduction and damage in the morphology of dermatophytic hyphae. In addition, the ex vivo onychomycosis model was effective in the establishment of infection by T. rubrum. Conclusion. Treatment with the quinoline-derivative lacquer showed a significant inhibitory effect on T. rubrum strain in this infection model. Finally, the compound presents high potential for application in a formulation such as nail lacquer as a possible treatment for dermatophytic onychomycosis.

Published
2021
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4. Quinolines derivatives as promising new antifungal candidates for the treatment of candidiasis and dermatophytosis

Author

Aline Rigon Zimmer, Thaís Carine Ruaro, Denise Diedrich, Luís Flávio de Oliveira, Simone Cristina Baggio Gnoatto, Pierre van de Weghe, Mickael Jean, Gabriella da Rosa Monte Machado, Mário Lettieri Teixeira, Saulo Fernandes de Andrade, Alexandre Meneghello Fuentefria, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Antifungal, medicine.medical_specialty, Antifungal Agents, Clinical Microbiology - Research Paper, medicine.drug_class, Cell Survival, Dermatophyte, [SDV]Life Sciences [q-bio], Microbial Sensitivity Tests, Pharmacology, Dermatófitos, medicine.disease_cause, Microbiology, Quinoline derivatives, 03 medical and health sciences, Medical microbiology, Chlorocebus aethiops, Media Technology, Medicine, Animals, [CHIM]Chemical Sciences, Toxicologia, Vero Cells, 030304 developmental biology, Candida, 0303 health sciences, 030306 microbiology, business.industry, Arthrodermataceae, Fungal resistance, Antifungal potential, Multiple drug resistance, análise [Compostos químicos], Quinolinas, Toxicity, Tinha, Candida spp, Quinolines, business, Antifúngicos
Abstract

Fungal infections have emerged as a current serious global public health problem. The main problem involving these infections is the expansion of multidrug resistance. Therefore, the prospection of new compounds with efficacy antifungal becomes necessary. Thus, this study evaluated the antifungal profile and toxicological parameters of quinolines derivatives against Candida spp. and dermatophyte strains. As a result, a selective anti-dermatophytic action was demonstrated by compound 5 (geometric means (GM = 19.14 μg ml−1)). However, compounds 2 (GM = 50 μg ml−1) and 3 (GM = 47.19 μg ml−1) have presented only anti-Candida action. Compounds 3 and 5 did not present cytotoxic action. Compound 5 did not produce dermal and mucosal toxicity. In addition, this compound showed the absence of genotoxic potential, suggesting safety for topical and systemic use. Quinolines demonstrated a potent anti-dermatophytic and anti-yeast action. Moreover, compound 5 presented an excellent toxicological profile, acting as a strong candidate for the development of a new effective and safe compound against dermatophytosis of difficult treatment. Electronic supplementary material The online version of this article (10.1007/s42770-020-00348-4) contains supplementary material, which is available to authorized users.

Published
2020
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5. Synthesis and evaluation of 1,3,4-oxadiazole derivatives for development as broad-spectrum antibiotics

Author

Annie Trautwetter, Gwennola Ermel, Cédric Tresse, Jean-Christophe Giard, Carlos Blanco, Richard Radigue, Pierre van de Weghe, Marion Thepaut, Reynald Gillet, Rafael Gomes Von Borowski, Fanny Demay, Sylvie Georgeault, Hong Hanh Le, Anne Dhalluin, Mickael Jean, Laboratoire de chimie moléculaire (LCM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Lille, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was supported by the Direction Générale de l’Armement (#ANR-14-ASTR-0001, France) and the Agence Nationale pour la Recherche under the frame of the Joint JPI-EC-AMR Project named 'Ribotarget - Development of novel ribosome-targeting antibiotics' (SNF No. 40AR40_185777, Europe)., ANR-14-ASTR-0001,antibio,Une nouvelle classe d'antibiotiques inhibiteurs de la trans-traduction bactérienne(2014), Jonchère, Laurent, Accompagnement spécifique des travaux de recherches et d’innovation défense - Une nouvelle classe d'antibiotiques inhibiteurs de la trans-traduction bactérienne - - antibio2014 - ANR-14-ASTR-0001 - ASTRID - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1)

Subjects
tmRNA, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, medicine.drug_class, Cell Survival, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Clinical Biochemistry, Antibiotics, Pharmaceutical Science, Oxadiazole, Microbial Sensitivity Tests, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, Gram-Positive Bacteria, 01 natural sciences, Biochemistry, Ribosome, chemistry.chemical_compound, Antibiotic resistance, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Cell Line, Tumor, Drug Discovery, Gram-Negative Bacteria, medicine, Humans, Molecular Biology, Oxadiazoles, biology, 010405 organic chemistry, Organic Chemistry, Pathogenic bacteria, Drug Synergism, Antimicrobial, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 0104 chemical sciences, Anti-Bacterial Agents, 010404 medicinal & biomolecular chemistry, chemistry, Trans-translation, Drug Design, Molecular Medicine, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacteria
Abstract

International audience; The reality and intensity of antibiotic resistance in pathogenic bacteria calls for the rapid development of new antimicrobial drugs. In bacteria, trans-translation is the primary quality control mechanism for rescuing ribo-somes arrested during translation. Because trans-translation is absent in eukaryotes but necessary to avoid ri-bosomal stalling and therefore essential for bacterial survival, it is a promising target either for novel antibiotics or for improving the activities of the protein synthesis inhibitors already in use. Oxadiazole derivatives display strong bactericidal activity against a large number of bacteria, but their effects on trans-translation were recently questioned. In this work, a series of new 1,3,4-oxadiazole derivatives and analogs were synthesized and assessed for their efficiency as antimicrobial agents against a wide range of gram-positive and gram-negative pathogenic strains. Despite the strong antimicrobial activity observed in these molecules, it turns out that they do not target trans-translation in vivo, but they definitely act on other cellular pathways.

Published
2019
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6. Probing the side chain tolerance for inhibitors of the CD95/PLCγ1 interaction

Author

Patrick Legembre, Ha Thanh Nguyen, Jean-Philippe Guégan, Pierre van de Weghe, Nicolas Levoin, Daniel Best, Mickael Jean, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Bioprojet-Biotech, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National Du Cancer, Ligue Contre le Cancer, Fondation ARC pour la Recherche sur le Cancer, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
Models, Molecular, Protein Conformation, Surface Properties, Peptidomimetic, Stereochemistry, [SDV]Life Sciences [q-bio], Static Electricity, Clinical Biochemistry, Druggability, Pharmaceutical Science, Lupus, Arginine, 01 natural sciences, Biochemistry, Protein–protein interaction, chemistry.chemical_compound, symbols.namesake, Drug Discovery, Side chain, Cell migration, Amino Acid Sequence, fas Receptor, Phospholipase, Molecular Biology, chemistry.chemical_classification, Phospholipase C gamma, 010405 organic chemistry, Hydrogen bond, Organic Chemistry, Hydrogen Bonding, Peptoid, Fas, 3. Good health, 0104 chemical sciences, Amino acid, 010404 medicinal & biomolecular chemistry, chemistry, Mutagenesis, symbols, CD95, Protein protein interaction, Thermodynamics, Molecular Medicine, van der Waals force, Hydrophobic and Hydrophilic Interactions, Aromatic, Protein Binding
Abstract

International audience; Proceeding our effort to study protein-protein interaction between the death receptor CD95 and phospholipase PLCγ1, we present in the current work chameleon-like traits of peptidomimetic inhibitors. Minute analysis of the interaction suggests that most of the binding energy relies on van der Waals contacts rather than more specific features, such as hydrogen bonds or salt bridges. The two most important positions of the peptoid for its interaction with PLCγ1 (Arg184 and Arg187) were modified to test this hypothesis. While Arg184 proves to be exchangeable for Trp, with no alteration in affinity, the nature of the amino acid replacing Arg187 is more dependent on its positive charge. However, affinity can be partially recovered by increasing van der Waals interactions. Overall, this study shows that for both positions, a subtle balance exists between hydrophobicity, surface contacts and affinity for CD95/PLCγ1, and provides information for the generation of new therapeutic compounds toward this druggable target.

Published
2019
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7. Correction to A Novel Covalent mTOR Inhibitor, DHM25, Shows in Vivo Antitumor Activity against Triple-Negative Breast Cancer Cells

Author

Hariniaina Rampanarivo, Mickael Jean, Amélie Fouqué, Patrick Legembre, Mac Dinh Hung, Kenji F. Shoji, Yves Collette, Marine Malleter, Rémy Castellano, Emmanuelle Josselin, Pierre van de Weghe, Olivier Delalande, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Structures et interactions moléculaires, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CRLCC Eugène Marquis (CRLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), and Bidaut, Ghislain

Subjects
Antitumor activity, Chemistry, In vivo, Covalent bond, Drug Discovery, Cancer research, Molecular Medicine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Discovery and development of mTOR inhibitors, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Triple-negative breast cancer, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract

International audience

Published
2019
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8. Lichen butyrolactone derivatives disrupt oral bacterial membrane

Author

Agnès Burel, Marylène Chollet-Krugler, Julien Vallet, Ali Chokr, Alaa Sweidan, Zohreh Tamanai-Shacoori, Latifa Bousarghin, Nolwenn Oliviero, Aurélie Sauvager, Sophie Tomasi, Nicolas Gouault, Pierre van de Weghe, Imen Smida, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Centre de Microscopie de Rennes (MRic), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Lebanese University [Beirut] (LU), Rennes I University, Association of Specialization and Scientific Orientation, Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Lichens, Metabolite, Cell, Lichen, Microbial Sensitivity Tests, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 01 natural sciences, Microbiology, Cell wall, Lactones, chemistry.chemical_compound, Drug Discovery, medicine, Pharmacology, Hplc analysis, Molecular Structure, biology, 010405 organic chemistry, Cell Membrane, Streptococcus gordonii, General Medicine, Porphyromanas gingivalis, biology.organism_classification, Anti-Bacterial Agents, 3. Good health, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, medicine.anatomical_structure, Membrane, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Butyrolactone, Antibacterial activity, Porphyromonas gingivalis, Bacteria
Abstract

International audience; We have previously demonstrated that out of the butyrolactones series synthesized based on the natural lichen metabolite lichesterinic acid, compound (B-13) was the most effective against oral bacteria. However, its antibacterial mechanism is still unknown. In this study, we have investigated its bacterial localization by synthesizing a fluorescently labeled B-13 with NBD while maintaining its antibacterial activity. We showed that this compound binds to Streptococcus gordonii cell surface, as demonstrated by HPLC analysis. By adhering to cell surface, B-13 induced cell wall disruption leading to the release of bacterial constituents and consequently, the death of S. gordonii, a Gram-positive bacterium. A Gram-negative counterpart, Porphyromanas gingivalis, showed also cracked and ruptured cells in the presence of B-13. Besides, we also demonstrated that the analog of B-13, B-12, has also induced disruption of P. gingivalis and S. gordonii. This study revealed that butyrolactones can be considered as potent antibacterial compounds against oral pathogens causing medical complications.

Published
2019
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9. Synthesis of peptidomimetics and chemo-biological tools for CD95/PLCγ1 interaction analysis

Author

Nicolas Levoin, Patrick Legembre, Amanda Poissonnier, Pierre van de Weghe, Ha Thanh Nguyen, Daniel Best, Mickael Jean, Pierre Vacher, Jean-Philippe Guégan, Florence Jouan, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe labellisée Ligue contre le Cancer, Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioprojet-Biotech, INCa PLBIO, Ligue Contre le Cancer, Fondation ARC, ANR PRCE, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], and UNICANCER-UNICANCER

Subjects
Peptidomimetic, Clinical Biochemistry, Pharmaceutical Science, Lupus, Biotin, Peptide, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Phospholipase, 01 natural sciences, Biochemistry, Cell Movement, Cell Line, Tumor, Drug Discovery, medicine, Humans, Cell migration, fas Receptor, Receptor, Molecular Biology, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 010405 organic chemistry, Chemistry, Phospholipase C gamma, Organic Chemistry, Fas, Fas receptor, 3. Good health, 0104 chemical sciences, Cell biology, Molecular Docking Simulation, 010404 medicinal & biomolecular chemistry, Apoptosis, CD95, Molecular Medicine, Th17, Peptidomimetics, medicine.symptom, Protein Multimerization, PPI inhibitor, Protein Binding
Abstract

The death receptor CD95 (also known as Fas) induces apoptosis through protein/protein association and the formation of the death-inducing signaling complex. On the other hand, in certain biological conditions, this receptor recruits different proteins and triggers the formation of another complex designated motility-inducing signaling complex, which promotes cell migration and inflammation. This pathway relies on a short sequence of CD95, called calcium-inducing domain (CID), which interacts with the phospholipase PLCγ1. To better understand how CID/PLCγ1 interaction occurs, we synthesized different α-AA peptides mimicking CID. Some of these peptidomimetics are as potent as the natural peptide to disrupt the CID/PLCγ1 interaction and cell migration, and showed improved pharmacokinetic properties. We also generated biotinyl- and palmitoyl-labelled peptidomimetics, useful chemico-biological tools to further explore the pro-inflammatory signal of CD95, which plays an important role in the pathogenesis of lupus and other autoimmune diseases.

Published
2019
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10. Modular Synthesis of Arylacetic Acid Esters, Thioesters, and Amides from Aryl Ethers via Rh(II)-Catalyzed Diazo Arylation

Author

Pierre van de Weghe, Daniel Best, Mickael Jean, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Aromatic compounds, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Chemical reaction, Catalysis, Arylations, Electron-rich arenes, Rhodium, Diazo reagents, chemistry.chemical_compound, Meldrum's acids, Chemical reactions, [CHIM]Chemical Sciences, Organic chemistry, Aryl ether, Modular synthesis, 010405 organic chemistry, Aryl, Organic Chemistry, Esters, Amides, 0104 chemical sciences, Anticancer compounds, chemistry, Reagent, Diazo, Arylacetic acids
Abstract

International audience; One-pot formation of arylacetic acid esters, thioesters, and amides via Rh(II)-catalyzed arylation of a Meldrum's acid-derived diazo reagent with electron-rich arenes is described. The methodology was used to efficiently synthesize an anticancer compound. © 2016 American Chemical Society.

Published
2016
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11. Disrupting the CD95-PLC gamma 1 interaction prevents Th17-driven inflammation

Author

Patrick Blanco, Amanda Poissonnier, Nicolas Levoin, Patrick Legembre, Lucie Morere, Pierre van de Weghe, Guennadi Kozlov, Sophie Martin, Isabelle Douchet, Ha Thanh Nguyen, Estibaliz Lazaro, Daniel Best, Raphael Pineau, Melissa Thomas, Jean-Philippe Guégan, Mickael Jean, Thomas Ducret, Pierre Vacher, Florence Jouan, Kalle Gehring, CRLCC Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Bioprojet-Biotech, McGill University = Université McGill [Montréal, Canada], Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, INCa PLBIO, Ligue Contre le Cancer, Fondation ARC, ANR PRCE, Fondation Arthritis, Canadian Institutes of Health Research [FRN-156276], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], and UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Lupus erythematosus, biology, Chemistry, Peptidomimetic, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Fas receptor, medicine.disease, 3. Good health, Cell biology, 03 medical and health sciences, 030104 developmental biology, biology.protein, medicine, HIV Protease Inhibitor, Ritonavir, FADD, medicine.symptom, Signal transduction, Molecular Biology, medicine.drug
Abstract

International audience; CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca2+ response via docking of PLC gamma 1 to the calcium-inducing domain (CID) within CD95. This signaling pathway induces accumulation of inflammatory Th17 cells in damaged organs of lupus patients, thereby aggravating disease pathology. A large-scale screen revealed that the HIV protease inhibitor ritonavir is a potent disruptor of the CD95-PLC gamma 1 interaction. A structure-activity relationship approach highlighted that ritonavir is a peptidomimetic that shares structural characteristics with CID with respect to docking to PLC gamma 1. Thus, we synthesized CID peptidomimetics abrogating both the CD95-driven Ca2+ response and transmigration of Th17 cells. Injection of ritonavir and the CID peptidomimetic into lupus mice alleviated clinical symptoms, opening a new avenue for the generation of drugs for lupus patients.

Published
2018
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12. Disrupting the CD95-PLCγ1 interaction prevents Th17-driven inflammation

Author

Amanda, Poissonnier, Jean-Philippe, Guégan, Ha Thanh, Nguyen, Daniel, Best, Nicolas, Levoin, Guennadi, Kozlov, Kalle, Gehring, Raphael, Pineau, Florence, Jouan, Lucie, Morere, Sophie, Martin, Mélissa, Thomas, Estibaliz, Lazaro, Isabelle, Douchet, Thomas, Ducret, Pierre, van de Weghe, Patrick, Blanco, Mickael, Jean, Pierre, Vacher, and Patrick, Legembre

Subjects
Inflammation, Male, Ritonavir, Phospholipase C gamma, Anti-Inflammatory Agents, Non-Steroidal, Drug Evaluation, Preclinical, Mice, Mutant Strains, Molecular Docking Simulation, Disease Models, Animal, Structure-Activity Relationship, Thiazoles, Protein Domains, Animals, Humans, Lupus Erythematosus, Systemic, Th17 Cells, Female, Peptidomimetics, fas Receptor
Abstract

CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca

Published
2018

13. Antibacterial activities of natural lichen compounds against Streptococcus gordonii and Porphyromonas gingivalis

Author

Alaa Sweidan, Marylène Chollet-Krugler, Aurélie Sauvager, Sophie Tomasi, Latifa Bousarghin, Martine Bonnaure-Mallet, Ali Chokr, Pierre van de Weghe, Lebanese University [Beirut] (LU), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Rennes I University, UMR CNRS 6226 (France), and Association of Specialization and Scientific Orientation (Lebanon) were behind supporting this research., Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Vulpinic acid (Vul) (PubChem CID: 54690323), Antibiotics, (+)-acetylportentol (A) (PubChem CID: 101282317), Lichen, 01 natural sciences, Methyl-beta-orcinolcarboxylate (M) (PubChem CID: 78435), chemistry.chemical_compound, antibacterial activity, Drug Discovery, (+)-Erythrin (E) (PubChem CID: 12308905), biology, Molecular Structure, Chemistry, Broth microdilution, Streptococcus gordonii, Variolaric acid (Var) (PubChem CID: 12444681), General Medicine, Lepraric acid (L) (PubChem CID: 12304992), 3. Good health, Anti-Bacterial Agents, Screening, Antibacterial activity, Porphyromonas gingivalis, Lichens, medicine.drug_class, Microbial Sensitivity Tests, Microbiology, Conhypoprotocetraric acid (C) (PubChem CID: 101282317), Cell Line, Tumor, medicine, Humans, [CHIM]Chemical Sciences, (+)-Roccellic acid (R) (PubChem CID: 11449446), Periodontal Diseases, Pharmacology, Mouth, Psoromic acid (P) (PubChem CID: 23725), Demethylbarbatic acid (D) (PubChem CID: 10450302), 010405 organic chemistry, Depsidone, Biofilm, biology.organism_classification, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, stomatognathic diseases, Biofilms, Hypoprotocetraric acid (H) (PubChem CID: 627044), Bacteria
Abstract

International audience; The oral bacteria not only infect the mouth and reside there, but also travel through the blood and reach distant body organs. If left untreated, the dental biofilm that can cause destructive inflammation in the oral cavity may result in serious medical complications. In dental biofilm, Streptococcus gordonii, a primary oral colonizer, constitutes the platform on which late pathogenic colonizers like Porphyromonas gingivalis, the causative agent of periodontal diseases, will bind. The aim of this study was to determine the antibacterial activity of eleven natural lichen compounds belonging to different chemical families and spanning from linear into cyclic and aromatic structures to uncover new antibiotics which can fight against the oral bacteria. The compounds were screened by broth microdilution assay. Three compounds were shown to have promising antibacterial activities where the depsidone core with certain functional groups constituted the best compound, psoromic acid, with the lowest MICs=11.72 and 5.86μg/mL against S. gordonii and P. gingivalis, respectively. The compounds screened had promising antibacterial activity which might be attributed to some important functional groups as discussed in our study. The best compounds did not induce the death of gingival epithelial carcinoma cells (Ca9-22). These results introduce new compounds having potent antibacterial activities against oral pathogens causing serious medical complications.

Published
2017
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14. Dynemicin A, Uncialamycin and Analogues

Author

Daniel Best, Mickael Jean, Pierre Van De Weghe, Daniel Best, Mickael Jean, and Pierre Van De Weghe

Subjects
Antineoplastic antibiotics
Abstract

Enediynes are natural products with highly active cytotoxicity and antibacterial activity, and thus have significant potential in the development of anti-cancer treatments. However, they are not readily available and can degrade rapidly during isolation; one solution is to produce them using total synthesis.Dynemicin A and uncialamycin are two such enediynes, with similar structures, for which total synthesis has been achieved. This book presents the isolation and preparation of these two compounds and their analogues through various synthesis strategies. Details of the structural elements essential to their anti-cancer activity are presented, with the objective of explaining and optimizing their biological activities and potential development as drugs. - Presents two natural ènediynes with similar structures whose total syntheses have been accomplished - Explores structural analogs of preparation for purposes of optimizing the anti-cancer activity - Describes the total syntheses of dynemicin A, the uncialamycine, as well as analogs by emphasizing the synthesis strategies adopted - Features studies of the biological activities and data to bring out the structural elements of these essential compounds

Published
2016

15. Cyclopentadienyliron dicarbonyl dimer: A simple tool for the hydrosilylation of aldehydes and ketones under air

Author

Pierre van de Weghe, Thais Cordeiro Jung, Gilles Argouarch, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), We thank Université de Rennes 1 and CNRS for financial support., Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Aldehydes, 010405 organic chemistry, Cyclopentadienyliron dicarbonyl dimer, Hydrosilylation, Iron, Process Chemistry and Technology, General Chemistry, Ketones, 010402 general chemistry, 01 natural sciences, Catalysis, 3. Good health, 0104 chemical sciences, chemistry.chemical_compound, chemistry, [CHIM]Chemical Sciences, Organic chemistry, Iron complex, Reduction
Abstract

International audience; The readily available iron complex [CpFe(CO)2]2 (1) exhibits good catalytic activity in the hydrosilylation of aldehydes and ketones in the presence of diethoxymethylsilane. The procedure described is air-tolerant and applicable to a wide range of substrates

Published
2016
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16. Design, synthesis and biological evaluation of potential antibacterial butyrolactones

Author

Marylène Chollet-Krugler, Pierre van de Weghe, Alaa Sweidan, Ali Chokr, Latifa Bousarghin, Sophie Tomasi, Martine Bonnaure-Mallet, Faculty of Engineering, Beirut, Lebanon, Microbiologie : Risques Infectieux, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Faculté de Chirurgie Dentaire de Rennes-Faculté d'Odontologie-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), FundingThe research was supported by Rennes I University, CNRS (France), Association of Specialization and Scientific Orientation (Liban) and Melanolichen Grant (France).AcknowledgmentsWe acknowledge Prof. J. Boustie (Head of PNSCM team) for his helpful discussion. We would also like to thank C. Le Lann and N. Oliviero (EA 1254—Rennes I university), and Nathalie Legrave (UMR CNRS 6226—Rennes I University) for their technical assistance., Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes - UFR d'Odontologie (UR Odontologie), Université de Rennes (UR)-Université de Rennes (UR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, medicine.drug_class, Stereochemistry, Cell Survival, Cytotoxicity, 030106 microbiology, Clinical Biochemistry, Antibiotics, Pharmaceutical Science, Lichen, Microbial Sensitivity Tests, 01 natural sciences, Biochemistry, Cell Line, 03 medical and health sciences, Lactones, Structure-Activity Relationship, Drug Discovery, medicine, [CHIM]Chemical Sciences, Humans, Molecular Biology, Alkyl, chemistry.chemical_classification, biology, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Chemistry, Macrophages, Organic Chemistry, Streptococcus gordonii, Butyrolactones, biology.organism_classification, In vitro, 0104 chemical sciences, Anti-Bacterial Agents, Antibacterial, Mechanism of action, Cell culture, Drug Design, Molecular Medicine, medicine.symptom, Antibacterial activity
Abstract

International audience; Novel butyrolactone analogues were designed and synthesized based on the known lichen antibacterial compounds, lichesterinic acids (B-10 and B-11), by substituting different functional groups on the butyrolactone ring trying to enhance its activity. All synthesized butyrolactone analogues were evaluated for their in vitro antibacterial activity against Streptococcus gordonii. Among the derivatives, B-12 and B-13 had the lowest MIC of 9.38 μg/mL where they have shown to be stronger bactericidals, by 2–3 times, than the reference antibiotic, doxycycline. These two compounds were then checked for their cytotoxicity against human gingival epithelial cell lines, Ca9–22, and macrophages, THP-1, by MTT and LDH assays which confirmed their safety against the tested cell lines. A preliminary study of the structure–activity relationships unveiled that the functional groups at the C4 position had an important influence on the antibacterial activity. An optimum length of the alkyl chain at the C5 position registered the best antibacterial inhibitory activity however as its length increased the bactericidal effect increased as well. This efficiency was attained by a carboxyl group substitution at the C4 position indicating the important dual role contributed by these two substituents which might be involved in their mechanism of action. © 2016 Elsevier Ltd

Published
2016
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18. The Prins Reaction Using Ketones: Rationalization and Application toward the Synthesis of the Portentol Skeleton

Author

Pierre van de Weghe, Nicolas Levoin, Maiwenn Jacolot, Mickael Jean, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Rennes Métropole, Région Bretagne, Université de Rennes 1, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
MESH: Molecular Structure, MESH: Ketones, 010402 general chemistry, 01 natural sciences, Biochemistry, Kinetic resolution, Computational chemistry, Spiro Compounds, MESH: Cyclization, MESH: Pyrans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Physical and Theoretical Chemistry, Pyrans, Molecular Structure, MESH: Kinetics, 010405 organic chemistry, Chemistry, Organic Chemistry, Rationalization (psychology), Stereoisomerism, Ketones, Prins reaction, MESH: Stereoisomerism, 0104 chemical sciences, Kinetics, MESH: Spiro Compounds, Cyclization
Abstract

International audience; We report a TMSI-promoted Prins cyclization reaction with ketones as carbonyl partners to prepare polysubstituted chiral spirotetrahydropyrans. In the presence of racemic 2-methylcyclohexanone a dynamic kinetic resolution occurred affording one stereoisomer. The observed enantiospecificity has been rationalized by DFT calculation.

Published
2011
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19. Intramolecular Imino Diels−Alder Reaction: Progress toward the Synthesis of Uncialamycin

Author

Sandy Desrat, Pierre van de Weghe, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Intramolecular reaction, Stereochemistry, Chemistry, Pharmaceutical, Chemistry, Organic, Anthraquinones, Alkenes, 010402 general chemistry, 01 natural sciences, Chemical synthesis, Medicinal chemistry, chemistry.chemical_compound, Anti-Infective Agents, X-Ray Diffraction, Enediyne, [CHIM]Chemical Sciences, Moiety, Diels–Alder reaction, Molecular Structure, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Organic Chemistry, Quinoline, Stereoisomerism, 0104 chemical sciences, 3. Good health, Oxygen, Models, Chemical, chemistry, Alkynes, Intramolecular force, Quinolines, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone
Abstract

International audience; We herein described an intramolecular imino Diels−Alder reaction promoted with BF3·OEt2/DDQ affording substituted quinolines. Using this procedure, we prepared the chiral quinoline moiety of the uncialamycin, a new enediyne natural product.

Published
2009
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20. Novel Chiral Molecular Tweezer from (+)-Usnic Acid

Author

Loïc Toupet, Pierre van de Weghe, Béatrice Legouin, Philippe Uriac, Sophie Tomasi, Arnaud Bondon, Substances Lichéniques et Photoprotection, Université de Rennes (UR), Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Plate-forme Rennaise d'Imagerie et Spectroscopie Structurale et Métabolique (PRISM), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Interactions cellulaires et moléculaires (ICM), De Villemeur, Hervé, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Centre National de la Recherche Scientifique (CNRS)-IFR140-Université de Rennes 1 (UR1)

Subjects
Models, Molecular, Stereochemistry, MESH: Molecular Structure, Molecular Conformation, Stereoisomerism, Crystallography, X-Ray, 010402 general chemistry, Heterocyclic Compounds, 4 or More Rings, 01 natural sciences, Biochemistry, Molecular conformation, chemistry.chemical_compound, Cyclohexanes, Models, MESH: Fluorenes, Molecule, Physical and Theoretical Chemistry, Binding site, Benzofurans, MESH: Heterocyclic Compounds with 4 or More Rings, Fluorenes, MESH: Molecular Conformation, Binding Sites, Crystallography, Molecular Structure, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Organic Chemistry, Usnic acid, Molecular, MESH: Benzofurans, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [CHIM.ORGA] Chemical Sciences/Organic chemistry, MESH: Crystallography, X-Ray, MESH: Cyclohexanes, MESH: Stereoisomerism, 0104 chemical sciences, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Binding Sites, X-Ray, Heterocyclic Compounds with 4 or More Rings, MESH: Models, Molecular
Abstract

International audience; A new chiral molecular tweezer was synthesized with (1R,2R)-1,2-diaminocyclohexane as spacer and two molecules of (+)-usnic acid as pincers. The ability of this molecular tweezer to bind 2,4,7-trinitrofluorenone was studied. A charge-transfer complex was formed in which TNF was sandwiched between the two usnic acid units with pi-pi-stacked aromatic interactions.

Published
2009
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21. Synthesis of Alkaloids ofGalipea officinalisby Alkylation of an α-Amino Nitrile

Author

Saurabh Shahane, Jean-Pierre Hurvois, Jean-Luc Renaud, Thierry Roisnel, Fadila Louafi, Julie Moreau, and Pierre van de Weghe

Subjects
Nitrile, biology, Organic Chemistry, Diastereomer, Methylation, Alkylation, Galipea, biology.organism_classification, Catalysis, Umpolung, chemistry.chemical_compound, chemistry, Hydrogenolysis, Organic chemistry, Physical and Theoretical Chemistry
Abstract

A new synthetic approach directed towards the synthesis of naturally occurring 2-alkyl-tetrahydroquinolines is described. The C–C bonds in the α position relative to the nitrogen atom were formed by the reversal of the polarity of the C=N bond of α-amino nitrile 6, which was prepared electrochemically from 1-(phenylethyl)-tetrahydroquinoline. A NaBH4-mediated reductive decyanation process furnished benzylic amines 16a–d as mixtures of diastereomers (50–60 % de). The catalytic hydrogenolysis of these amines was performed in the presence of Pearlman's catalyst to give the tetrahydroquinolines 17a–d in yields ranging from 70 % to 95 %. Methylation of the free nitrogen atom afforded the title compounds 1–4 in 70–90 % yields.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Published
2008
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22. Synergistic Effect of the TiCl4/p-TsOH Promoter System on the Aza-Prins Cyclization

Author

Claudia Lalli, Thierry Roisnel, Pierre van de Weghe, Vianney Durel, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
010405 organic chemistry, Stereochemistry, Organic Chemistry, Diastereomer, Synergistic combination, Prins reaction, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, chemistry.chemical_compound, chemistry, [CHIM]Chemical Sciences, Amine gas treating, Piperidine, Lewis acids and bases, Brønsted–Lowry acid–base theory
Abstract

International audience; A novel aza-Prins cyclization promoted by a synergistic combination between a Lewis acid and a Brønsted acid to efficiently afford piperidines is described. Contrary to what has been previously reported in the literature, the generality of the reaction employing N-alkyl, N-aryl, and nonprotected homoallylamines has been demonstrated. The reaction is highly diastereoselective depending on the homoallylic amine used, N-PMP homoallyl amine leading preferentially to the trans diastereomer, and free homoallylamine affording the deprotected piperidine as single cis diastereomer

Published
2016
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24. Dynemicin A

Author

Daniel Best, Mickael Jean, and Pierre van de Weghe

Subjects
chemistry.chemical_compound, Dynemicin A, chemistry, Sodium iodide, Microorganism, Extraction (chemistry), Absolute configuration, Enantioselective synthesis, Organic chemistry, Derivative (chemistry), Stereocenter
Abstract

Dynemicin A 2-1 was first isolated in the mid-1980s from Micromonospora chersina, a soil microorganism collected in the state of Gujarat in India. From a 200 L culture broth, it was possible to obtain 5.7 mg of 2-1 as a violet amorphous solid after extraction and purification. The production of 2-1 was later improved by the addition of sodium iodide to the culture medium, which allowed isolation of up to 2 g of 2-1 from a 10 000 L fermentation broth. The presence of ionexchanging resins in the neutral culture medium also improved the efficiency. The spectroscopic characterization was facilitated by converting dynemicin A into the triacetate derivative 2-2, which is soluble in most organic solvents, and allowed unequivocal structural determination by single-crystal X-ray diffraction. Although the structure obtained by X-ray diffraction revealed the relative configurations of stereogenic centers, the absolute configuration of 2-1 was not firmly established until the first total asymmetric synthesis described by Myers in 1995 and 1997.

Published
2016
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26. A Novel Covalent mTOR Inhibitor, DHM25, Shows in Vivo Antitumor Activity against Triple-Negative Breast Cancer Cells

Author

Yves Collette, Kenji F. Shoji, Olivier Delalande, Rémy Castellano, Mac Dinh Hung, Patrick Legembre, Marine Malleter, Mickael Jean, Emmanuelle Josselin, Pierre van de Weghe, Hariniaina Rampanarivo, Amélie Fouqué, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Oncogenesis Stress Signaling (OSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Institut National Du Cancer, Ministère de l'Enseignement Supérieur et de la Recherche, Fondation ARC pour la Recherche sur le Cancer, Comité du Morbihan, Ligue Nationale Contre le Cancer, Comité de Maine-et-Loire, Ligue Nationale Contre le Cancer, Comité des Côtes-d'Armor, Ligue Nationale Contre le Cancer, Comité du Finistère, Ligue Nationale Contre le Cancer, Comité d’Ille-et-Vilaine, Ligue Nationale Contre le Cancer, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)

Subjects
Models, Molecular, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Breast Neoplasms, Metastasis, Mice, Structure-Activity Relationship, Mice, Inbred NOD, Cell Line, Tumor, Drug Discovery, medicine, Animals, Humans, Kinome, Benzopyrans, Kinase activity, Phosphorylation, PI3K/AKT/mTOR pathway, Triple-negative breast cancer, Phosphoinositide-3 Kinase Inhibitors, Kinase, Chemistry, TOR Serine-Threonine Kinases, RPTOR, medicine.disease, Molecular biology, 3. Good health, Oncogene Protein v-akt, Cancer cell, Cancer research, Molecular Medicine, Female, Drug Screening Assays, Antitumor, Signal Transduction
Abstract

International audience; Constitutive activation of the PI3K/mTOR signaling pathway contributes to carcinogenesis and metastasis in most, if not all, breast cancers. From a chromene backbone reported to inhibit class I PI3K catalytic subunits, several rounds of chemical syntheses led to the generation of a new collection of chromologues that showed enhanced ability to kill PI3K-addicted cancer cells and to inhibit Akt phosphorylation at serine 473, a hallmark of PI3K/mTOR activation. This initial screen uncovered a chromene designated DHM25 that exerted potent antitumor activity against breast tumor cell lines. Strikingly, DHM25 was shown to be a selective and covalent inhibitor of mTOR using biochemical and cellular analyses, modeling, and a large panel of kinase activity assays spanning the human kinome (243 kinases). Finally, in vivo, this novel drug was an efficient inhibitor of growth and metastasis of triple-negative breast cancer cells, paving the way for its clinical application in oncology

Published
2015
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27. A simple spiroepoxide as methionine aminopeptidase-2 inhibitor: synthetic problems and solutions

Author

Céline Tarnus, Pierre van de Weghe, Jacques Eustache, and Vincent Rodeschini

Subjects
chemistry.chemical_compound, Heptane, chemistry, Simple (abstract algebra), Stereochemistry, Organic Chemistry, Drug Discovery, Substrate (chemistry), Metathesis, Biochemistry, METAP2, Derivative (chemistry)
Abstract

The preparation of a simple 1-oxa-spiro[2.4]heptane derivative is described. Observations made in the course of the synthesis show again that apparently minor structural modifications of the dienic substrate exert a strong influence on the ring-closing metathesis outcome and that the efficient construction of even simple but highly substituted systems by RCM may constitute a synthetic challenge.

Published
2005
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28. Recent Developments in Palladium-Catalyzed Coupling Reactions

Author

Pierre van de Weghe

Subjects
Chemistry, Negishi coupling, Hydride, Aryl, Organic Chemistry, Heteroatom, chemistry.chemical_element, General Medicine, Biochemistry, Combinatorial chemistry, Oxidative addition, Coupling reaction, chemistry.chemical_compound, Organic chemistry, Palladium-catalyzed coupling reactions, Palladium
Abstract

During the last few years major advances in Pd-catalyzed coupling reactions have been described; new catalyst systems based on bulky, electron-rich phosphines have been developed. This short report focuses on the recent progress in this area. Palladium-catalyzed cross-coupling reactions have become one of the most powerful carbon-carbon and carbon- heteroatom bond forming reactions and have been widely employed in total synthesis (1). Whereas a wide range of aryl and vinyl halides with main group organometallic derivatives can be used in the Suzuki-Miyaura and Negishi reactions, few examples were reported with sterically hindered aryl halides and alkyl halides that possess β - hydrogen atoms, the problem with the latter being fast β- hydride elimination after oxidative addition to palladium (Scheme 1). Recent improvements in this field are the result of the development of new ligands such as bulky, electron- rich phosphines (2). This report proposes a short, non exhaustive overview of the recent progress in this area.

Published
2005
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29. Enantioselective Approaches to Potential MetAP-2 Reversible Inhibitors

Author

Céline Tarnus, Emmanuel Salomon, Pierre van de Weghe, Jacques Eustache, and Vincent Rodeschini

Subjects
Addition reaction, Cyclohexanones, Stereochemistry, Chemistry, Organic Chemistry, Molecular Conformation, Enantioselective synthesis, Metalloendopeptidases, Stereoisomerism, Biological activity, Aminopeptidases, Chemical synthesis, Deprotonation, Cyclohexanes, Fatty Acids, Unsaturated, Epoxy Compounds, Molecule, Stereoselectivity, Enzyme Inhibitors, Sesquiterpenes, Conjugate
Abstract

[reaction: see text] Enantioselective deprotonation of 4-substituted cyclohexanones and highly stereoselective conjugate addition of higher order mixed cuprates were the key steps in a concise synthesis of fumagalone-related molecules. The origin of the (low) biological activity of the new compounds as compared to fumagalone is briefly discussed.

Published
2005
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30. MetAP-2 Inhibitors Based on the Fumagillin Structure. Side-Chain Modification and Ring-Substituted Analogues

Author

Jean-Guy Boiteau, Céline Tarnus, Jacques Eustache, Vincent Rodeschini, and Pierre van de Weghe

Subjects
Models, Molecular, Magnetic Resonance Spectroscopy, Chemistry, Stereochemistry, Organic Chemistry, Metalloendopeptidases, Angiogenesis Inhibitors, Ring (chemistry), Metathesis, Aminopeptidases, Chemical synthesis, Semisynthesis, Cyclohexanes, Fatty Acids, Unsaturated, medicine, Side chain, Fumagillin, Sesquiterpenes, medicine.drug
Abstract

The preparation of a series of new fumagillin-derived MetAP-2 inhibitors is described. The synthetic approach was designed so as to permit modification of the fumagillin backbone at sites inaccessible through semisynthesis or previously existing total syntheses. An Evans aldolization and a ring-closing metathesis allowed the preparation of a pivotal intermediate which could then be functionalized in various ways using already established or newly developed methodologies.

Published
2003
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31. ChemInform Abstract: Enantioselective Prins Cyclization: BINOL-Derived Phosphoric Acid and CuCl Synergistic Catalysis

Author

Claudia Lalli and Pierre van de Weghe

Subjects
chemistry.chemical_compound, chemistry, Enantioselective synthesis, Organic chemistry, Synergistic catalysis, General Medicine, Prins reaction, Phosphoric acid, Catalysis
Abstract

The first enantioselective Prins cyclization is catalyzed by a combination of a chiral BINOL-derived bis-phosphoric acid and CuCl.

Published
2014
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32. Enantioselective Prins cyclization: BINOL-derived phosphoric acid and CuCl synergistic catalysis

Author

Pierre van de Weghe, Claudia Lalli, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Naphthols, 010402 general chemistry, 01 natural sciences, Catalysis, Stereocenter, chemistry.chemical_compound, Materials Chemistry, Organic chemistry, [CHIM]Chemical Sciences, Synergistic catalysis, Phosphoric Acids, Phosphoric acid, Tandem, 010405 organic chemistry, Chemistry, Primed In Situ Labeling, Metals and Alloys, Enantioselective synthesis, Stereoisomerism, General Chemistry, [CHIM.CATA]Chemical Sciences/Catalysis, Prins reaction, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Cyclization, Ceramics and Composites, Copper
Abstract

International audience; The first catalytic enantioselective Prins cyclization is disclosed. The reaction is catalyzed by the combination of a chiral BINOL-derived bis-phosphoric acid and CuCl. The process consists of a tandem Prins/Friedel-Crafts cyclization that affords the hexahydro-1H-benzo[f]isochromenes products with three new contiguous stereogenic centers in high yields, and good enantio- and excellent diastereoselectivities.

Published
2014
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33. Palladium-catalyzed arylation of vinylic acetates. Phosphine ligand influenced regioselectivity

Author

Mickael Jean, Jacques Renault, and Pierre van de Weghe

Subjects
chemistry.chemical_classification, Aryl, Organic Chemistry, Regioselectivity, chemistry.chemical_element, Methoxide, Biochemistry, Medicinal chemistry, Aldehyde, Coupling reaction, Catalysis, chemistry.chemical_compound, chemistry, Drug Discovery, Organic chemistry, Phosphine, Palladium
Abstract

A palladium-catalyzed coupling reaction of aryl bromides with vinylic acetates in the presence of tributyltin methoxide has been described. The a-arylation aldehyde product and the aryl ketone were obtained in the presence of P(t-Bu)3 and P(o-Tol)3, respectively.

Published
2009
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34. Synthesis of 1-arylidene-2,3-dihydro-1H-inden-2-ols through a tandem carbopalladation/Suzuki–Miyaura sequence

Author

Pierre van de Weghe, Jean-François Cupif, Philippe Uriac, and Estelle Marchal

Subjects
Tandem, Chemistry, Stereochemistry, Organic Chemistry, Drug Discovery, Stereoselectivity, Biochemistry, Sequence (medicine)
Abstract

A regio- and stereoselective synthesis of arylidene indenols has been developed. The key step involves a palladium-catalyzed tandem carbocyclization/Suzuki–Miyaura sequence.

Published
2008
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35. Ring closing metathesis as an efficient approach to branched cyclitols and aminocyclitols: a short synthesis of valiolamine

Author

Didier Le Nouen, Christiane Strehler, Jacques Eustache, Odile Sellier, and Pierre van de Weghe

Subjects
Ring-closing metathesis, Chemistry, Cyclohexenes, Organic Chemistry, Drug Discovery, Valiolamine, Organic chemistry, Biochemistry
Abstract

Ring closing metathesis of sugar-derived 1,6 dienes is the key step for the construction of highly functionnalized cyclohexenes, precursors of branched cyclitols and aminocyclitols. The method has been used for a short synthesis of valiolamine.

Published
1999
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36. Lanthanide iodides, a new family of efficient Lewis acid catalysts

Author

Pierre van de Weghe, Jacqueline Collin, and Nicolas Giuseppone

Subjects
Lanthanide, Ligand, Chemistry, Cycloaddition, Catalysis, Inorganic Chemistry, Cyclopentadienyl complex, Aldol reaction, Nucleophile, Polymer chemistry, Materials Chemistry, Organic chemistry, Lewis acids and bases, Physical and Theoretical Chemistry
Abstract

Samarium diiodide and other lanthanide iodides are very efficient Lewis acid catalysts for numerous reactions such as Mukaiyama aldol and Michael reactions, preparation of enoxysilanes, cycloaddition reactions and ring opening of oxiranes by silylated nucleophiles or amines. Activities and selectivities of catalysts vary with the nature of the metal and the ligands for some reactions. Lanthanide iodides coordinated by a cyclopentadienyl ligand with an asymmetric center and an ether function on a pendant chain have been characterized and tested for catalysis: low enantioselectivities are observed for complexes with intramolecular coordination.

Published
1998
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38. Synthesis of stachybotrin C and all of its stereoisomers: structure revision

Author

Mickael Jean, Naresh Tumma, Arnaud Bondon, Maiwenn Jacolot, Srivari Chandrasekhar, Pierre van de Weghe, Institut des Sciences Chimiques de Rennes (ISCR), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Plate-forme Rennaise d'Imagerie et Spectroscopie Structurale et Métabolique (PRISM), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Indoles, Molecular Structure, 010405 organic chemistry, Chemistry, Stereochemistry, Natural compound, Organic Chemistry, Absolute configuration, Total synthesis, Stereoisomerism, 010402 general chemistry, 01 natural sciences, Combinatorial chemistry, 3. Good health, 0104 chemical sciences, Stereocenter, Stachybotrin C, Benzopyrans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract

International audience; We disclose the first total synthesis of stachybotrin C, a potent neuroprotective natural compound. All of the four stereoisomers have been prepared and fully characterized with the aim to attribute the absolute configuration of the two adjacent stereocenters of the stachybotrin C.

Published
2013
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39. ChemInform Abstract: When the Nine-Membered Enediynes Play Hide and Seek

Author

Pierre van de Weghe, Mickael Jean, and Sophie Tomasi

Subjects
Chemistry, Hide and seek, General Medicine, Combinatorial chemistry
Abstract

The lack of stability of the 9-membered enediynes not associated with an apoprotein may explain the low number of isolated natural compounds containing this core. To overcome such a problem, particular attention should be paid during the process of extraction and isolation of secondary metabolites, especially from microorganisms such as actinomycetes in order to identify the non-cycloaromatized derivatives.

Published
2013
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41. Ring opening reactions of epoxides catalyzed by samarium iodides

Author

Jacqueline Collin and Pierre van de Weghe

Subjects
Samarium, Primary (chemistry), chemistry, Organic Chemistry, Drug Discovery, chemistry.chemical_element, Organic chemistry, Ring (chemistry), Biochemistry, Medicinal chemistry, Catalysis
Abstract

Sml2(THF)2 catalyzes the ring opening of epoxides by trimethylsilylazide, trimethylsilylcyanide and primary and secondary amines. High regioselectivities are observed in specific cases.

Published
1995
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42. Synthetic studies towards Stachybotrin C

Author

Mickael Jean, Maiwenn Jacolot, Pierre van de Weghe, Naresh Tumma, Srivari Chandrasekhar, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
pyrano-isoindolinone, cyclization, 010405 organic chemistry, natural products, spiro compounds, Organic Chemistry, Intermolecular force, Acetal, 010402 general chemistry, 01 natural sciences, Chemical synthesis, 0104 chemical sciences, 3. Good health, Benzopyran, chemistry.chemical_compound, chemistry, Moiety, Stachybotrin C, Phenol, Organic chemistry, Phenols, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Abstract

International audience; The preparation of racemic des-hydroxy stachybotrin C is described. Different approaches have been studied. Observations made in the course of the synthesis show the efficiency of the intermolecular cyclization between the diethyl acetal 19 and phenol 12 leading to the benzopyran moiety 17.

Published
2012
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43. When the nine-membered enediynes play hide and seek

Author

Sophie Tomasi, Mickael Jean, Pierre van de Weghe, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Molecular, Molecular Structure, 010405 organic chemistry, Chemistry, Stereochemistry, Hide and seek, Organic Chemistry, MESH: Molecular Structure, 010402 general chemistry, 01 natural sciences, Biochemistry, 3. Good health, 0104 chemical sciences, Physical and Theoretical Chemistry, Enediynes, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Enediynes, MESH: Models, Molecular
Abstract

International audience; The lack of stability of the 9-membered enediynes not associated with an apoprotein may explain the low number of isolated natural compounds containing this core. To overcome such a problem, particular attention should be paid during the process of extraction and isolation of secondary metabolites, especially from microorganisms such as actinomycetes in order to identify the non-cycloaromatized derivatives.

Published
2012
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44. Unprecedented synergistic effects between weak Lewis and Brønsted acids in Prins cyclization

Author

Pierre van de Weghe, René Grée, Prashant Borkar, J. S. Yadav, B. V. Subba Reddy, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Indo-French 'Joint Laboratory for Sustainable Chemistry at Interfaces', CNRS, France, CSIR, India., Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
Aldehydes, 010405 organic chemistry, Stereochemistry, Chemistry, Metals and Alloys, General Chemistry, Prins reaction, 010402 general chemistry, 01 natural sciences, Catalysis, 0104 chemical sciences, 3. Good health, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Cyclization, MESH: Lewis Acids, Materials Chemistry, Ceramics and Composites, Organic chemistry, MESH: Aldehydes, Lewis acids and bases, MESH: Cyclization, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Brønsted–Lowry acid–base theory, Lewis Acids
Abstract

International audience; Novel synergistic effects between Lewis and Brønsted acids in Prins cyclization are reported. Non-reactive Lewis acids and non-reactive Brønsted acids, which failed to perform Prins cyclization when used alone, have shown remarkable synergistic effects when used in combination to perform the reaction successfully.

Published
2012
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45. A DFT-D evaluation of the complexation of a molecular tweezer with small aromatic molecules

Author

Béatrice Legouin, Pierre van de Weghe, Jean-Yves Le Questel, Jérôme Graton, Philippe Uriac, Denis Jacquemin, Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Région des Pays de la Loire, Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
010304 chemical physics, Chemistry, Binding energy, Ab initio, General Physics and Astronomy, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Non specific, Computational chemistry, 0103 physical sciences, Molecule, Density functional theory, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Physical and Theoretical Chemistry, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Dispersion (chemistry)
Abstract

International audience; We use dispersion-corrected density functional theory approaches (DFT-D) to investigate the structure and properties of complexes constituted of an aromatic tweezer and aromatic molecules. It turns out that a B97-D/6-31G(d) geometry optimisation yields reasonably accurate structural parameters, whereas larger basis sets and the latest DFT-D models are required to adequately mimic the complexation energies measured through NMR experiments. This contribution highlights that ab initio schemes may be pertinent to investigate the binding energies of large association complexes, even when the studied interaction is relatively weak and shows a non specific character, with a significant dispersion contribution.

Published
2012
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46. Molecular Tweezers in Host-Guest Complexes: A Computational Study through a DFT-D Approach

Author

Jean-Yves Le Questel, Pierre van de Weghe, Philippe Uriac, François Besseau, Béatrice Legouin, Denis Jacquemin, Jérôme Graton, Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), European Research Council (ERC), Région des Pays de la Loire, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
010405 organic chemistry, Chemistry, Rational design, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Organic molecules, General Energy, Computational chemistry, Density functional theory, Physical and Theoretical Chemistry, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular tweezers, Host (network), Equilibrium constant
Abstract

International audience; The interactions of small organic molecules with a recently designed molecular tweezer have been modeled using density functional theory approaches. The weak values of the complexation constants of the different compounds make the computations particularly challenging. Nevertheless, the selected theoretical approach is shown to be able to detect several outliers that have been then reexamined by experimental means. The autoassociation, as cyclic dimers, of two carboxylic acids is shown to significantly disturb the 1:1 ligand@host equilibrium constants. Indeed, in CH2Cl2 solutions, the complexes mainly present a 2:1 ligand@host structure. This investigation is a further step toward the rational design of molecular tweezers.

Published
2012
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47. Diiodosamarium, a catalyst precursor for diels-alder and hetero diels-alder reactions

Author

Pierre van de Weghe and Jacqueline Collin

Subjects
chemistry.chemical_classification, Cyclopentadiene, Organic Chemistry, Binary compound, Biochemistry, Catalysis, chemistry.chemical_compound, Hydrocarbon, chemistry, Drug Discovery, Diels alder, Organic chemistry, Aliphatic compound, Enone, Isoprene
Abstract

SmI2 presents catalystic activity for Diels-Alder reactions between cyclopentadiene or isoprene and various dienophiles, and for hetero Diels-Alder reactions.

Published
1994
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49. Setbacks and Hopes: En Route to the Synthesis of Uncialamycin

Author

Mickael Jean, Sandy Desrat, Pierre van de Weghe, Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Rennes Métropole, Région Bretagne, Université de Rennes 1, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Natural product, Enediyne, 010405 organic chemistry, Stereochemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Acetylide, Organic Chemistry, Quinoline, Total synthesis, Uncialamycin, 010402 general chemistry, Ring (chemistry), 01 natural sciences, Biochemistry, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Drug Discovery, Moiety
Abstract

International audience; We herein report a new approach toward the synthesis of uncialamycin, an enediyne natural product isolated from the Streptomyces uncialis, bacteria present on the surface of the lichen Cladonia uncialis. A model for the preparation of uncialamycin has been achieved through a reaction cascade, an acetylide addition to the activated quinoline moiety, and a ring closure reaction as key steps.

Published
2011
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50. Gold-catalyzed intramolecular hydroarylation of olefins. Scope evaluation and preliminary mechanistic studies

Author

Pierre van de Weghe, Mickael Jean, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1, Région Bretagne, Rennes Métropole, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)

Subjects
Olefin fiber, Reaction mechanism, Intramolecular reaction, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Gold catalysis, Electrophilic aromatic substitution, 010402 general chemistry, 01 natural sciences, Biochemistry, Mechanistic studies, 0104 chemical sciences, Catalysis, Intramolecular hydroarylation, Electrophilic substitution, Intramolecular force, Drug Discovery, Kinetic isotope effect, Organic chemistry
Abstract

International audience; We report a gold-catalyzed intramolecular hydroarylation of unactivated olefins using a combination of AuCl3/AgOTf as the catalytic system affording dihydrobenzopyrans, tetralins and tetrahydroquinolines in good yields. For our preliminary mechanistic studies, we have investigated the kinetic isotope effects with deuterated arene compounds and found that this catalytic hydroarylation is consistent with an electrophilic aromatic substitution process.

Published
2011
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