title: Experimental and theoretical studies on the effect of the oxo group in 1,4-benzodiazepines.
abstract: Two families of regioisomeric 1,4-benzodiazepines, 4-benzyl-3H-benzo[e][1,4]diazepin-5-ones and 4-benzoyl-4,5-dihydro-3H-benzo[e][1,4]diazepines, have been synthesized through a similar Ugi/reduction cyclization sequence. Their conformation and stability depend on the position of the tautomeric imine/enamine equilibrium present in the diazepine nucleus, which in turn depends on the relative position of the carbonyl group adjacent to the nitrogen at the 4-position in the benzodiazepine system. Moreover, the electrophilic center on the imine tautomer is essential for the antitumor activity of some benzodiazepines as a DNA binding position. The mechanism of tautomerization in the presence or absence of the oxo group has been studied computationally using DFT methods (B3LYP/6-31G** level).
authors.affiliation: Chemistry Department, Faculty of Science, University of Burgos, 09001-Burgos, Spain. magaval@ubu.es.
authors.forename: Pablo
authors.initials: P
authors.lastname: Pertejo
authors.forename: María
authors.initials: M
authors.lastname: García-Valverde
authors.forename: Pablo
authors.initials: P
authors.lastname: Peña
authors.forename: Nicolás A
authors.initials: NA
authors.lastname: Cordero
authors.forename: Tomás
authors.initials: T
authors.lastname: Torroba
authors.forename: Alfonso
authors.initials: A
authors.lastname: González-Ortega
mesh_terms: D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry; D008962:Models, Theoretical
chemical_list: D001569:Benzodiazepines