An Unusual Synthesis of N-Unsubstituted Benzazepinones

Béatrice Quiclet-Sire (1) , Ngoc Diem My Tran (1) , Samir Z. Zard (1)

1 DCSO - Laboratoire de synthèse organique

We describe here an unexpected route to N-unsubstituted benzazepinone we discovered while examining a radical-based approach to cyclic hydroxamic acids. The strong chelating ability of hydroxamic acids toward metal ions such as zinc has made them popular targets for medicinal chemists. Numerous members of this family have indeed been reported to be potent inhibitors of histone deacetylase and matrix metalloproteinases.(1) Other interesting biological properties include antibiotic, antifungal, anti-inflammatory and anticancer activities.(1, 2) While most hydroxamic acids described are linear derivatives, such as the antibiotic fosmidomycin 1, a few cases where the hydroxamate motif is part of a ring appear to be particularly interesting (Figure 1). Examples include cobactin T, a siderophore growth promoter isolated from mycobacteria,(3) and PF-04859989, 3, an irreversible kynurenine aminotransferase II inhibitor developed by Pfizer for treating schizophrenia.(4)

Béatrice Quiclet-Sire, Ngoc Diem My Tran, Samir Z. Zard. An Unusual Synthesis of N-Unsubstituted Benzazepinones. Organic Letters, 2012, 14 (21), pp.5514-5517. ⟨10.1021/ol3026044⟩. ⟨hal-00967573⟩