2-(Substituted amino)-8-azachromones from 4,6-Diaryl-2-pyridones: A Synthetic Strategy toward Compounds of Broad Structural Diversity

Steve Saulnier (1) , Rayane Ghoteimi (1) , Christophe Mathé (1) , Suzanne Peyrottes (2) , Jean-Pierre Uttaro (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

3-Acetoacetyl-4,6-diaryl-2-pyridones are synthesized in three steps from chalcones and then condense with carbon disulfide to afford 8-azachromones containing a methylthio group at C2. This leaving group offers an entry point for the insertion of more complex moieties via nucleophilic substitution. For this purpose, N-nucleophiles are explored according to their positions in the Mayr's nucleophilicity scale (N parameter), and three main classes are distinguished depending on whether the substitution takes place from their neutral forms, from their deprotonated anionic forms, or under nucleophilic catalysis. A broad range of primary and secondary amines may be inserted by this method, including enantiomerically pure amino acids, enabling us to explore structural diversity.

Domaines: Chimie organique; Chimie thérapeutique; Biochimie, Biologie Moléculaire

Steve Saulnier, Rayane Ghoteimi, Christophe Mathé, Suzanne Peyrottes, Jean-Pierre Uttaro. 2-(Substituted amino)-8-azachromones from 4,6-Diaryl-2-pyridones: A Synthetic Strategy toward Compounds of Broad Structural Diversity. Journal of Organic Chemistry, 2020, 85 (18), pp.11778-11793. ⟨10.1021/acs.joc.0c01561⟩. ⟨hal-03007536⟩