Practical and Metal-Free Synthesis of Novel Enantiopure Amides Containing the Potentially Bioactive 5-Nitroimidazole Moiety.
We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pureN-tert-butanesulfinimine. Then, theN-tert-butanesulfinyl-protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles.
Aix-Marseille Université, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille CEDEX 05, France. cedric.spitz@univ-amu.fr.
Cédric
C
Spitz
Aix-Marseille Université, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille CEDEX 05, France. fanny.mathias@laposte.net.
Fanny
F
Mathias
Aix-Marseille Université, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille CEDEX 05, France. gamal.giuglio-tonolo@univ-amu.fr.
Alain Gamal
AG
Giuglio-Tonolo
Aix-Marseille Université, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille CEDEX 05, France. thierry.terme@univ-amu.fr.
Thierry
T
Terme
Aix-Marseille Université, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille CEDEX 05, France. patrice.vanelle@univ-amu.fr.
Patrice
P
Vanelle
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000737:chemistry*; D013237:Stereoisomerism
D000577:Amides; D009593:Nitroimidazoles; C052587:4-nitroimidazole
5-nitroimidazoles; amides; metal-free