Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues

Autor: Stéphane Fontanay, Stéphanie Philippot, Yury S. Halauko, Ghenia Bentabed-Ababsa, Floris Chevallier, Oleg A. Ivashkevich, Elisabeth Nagaradja, Mathieu Scalabrini, Raphaël E. Duval, Thierry Roisnel, Vadim E. Matulis, Florence Mongin
Přispěvatelé: 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), Laboratoire de Synthèse Organique Appliquée, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), UNESCO Chair of Belarusian State University, Minsk, Belarusian State University, We gratefully acknowledge Région Bretagne for financial support to E.N. F.M. also thank the Institut Universitaire de France and Rennes Métropole for financial support., 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 de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Base (chemistry)
Clinical Biochemistry
Molecular Conformation
Triazole
Pharmaceutical Science
Antineoplastic Agents
Microbial Sensitivity Tests
Antiproliferative activity
Resveratrol
Crystallography
X-Ray
Gram-Positive Bacteria
010402 general chemistry
01 natural sciences
Biochemistry
chemistry.chemical_compound
Suzuki reaction
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
Cell Line
Tumor
Gram-Negative Bacteria
Stilbenes
Drug Discovery
Humans
Phenyl group
Organic chemistry
[CHIM]Chemical Sciences
CH-acidity
Molecular Biology
Cell Proliferation
chemistry.chemical_classification
Deprotonative metalation
010405 organic chemistry
Aryl
Organic Chemistry
Triazoles
Anti-Bacterial Agents
0104 chemical sciences
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
chemistry
Resveratrol analogue
Molecular Medicine
Antiproliferative effect
Antibacterial activity
Zdroj: Bioorganic and Medicinal Chemistry
Bioorganic and Medicinal Chemistry, Elsevier, 2015, 23 (19), pp.6355-6363. ⟨10.1016/j.bmc.2015.08.031⟩
Bioorganic and Medicinal Chemistry, 2015, 23 (19), pp.6355-6363. ⟨10.1016/j.bmc.2015.08.031⟩
ISSN: 0968-0896
1464-3391
DOI: 10.1016/j.bmc.2015.08.031⟩
Popis: International audience; 1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2’-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line.
Databáze: OpenAIRE
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