Natural dibenzoxazepinones from leaves of Carex distachya: Structural elucidation and radical scavenging activity Antonio Fiorentino, * Brigida D’Abrosca, Severina Pacifico, Giuseppe Cefarelli, Piera Uzzo and Pietro Monaco Dipartimento di Scienze della Vita, Seconda Universita ` degli studi di Napoli, via Vivaldi 43, 81100 Caserta, Italy Received 6 October 2006; revised 31 October 2006; accepted 1 November 2006 Available online 6 November 2006 Abstract—Two new dibenzoxazepinones have been isolated from the leaves of Carex distachya, an herbaceous plant growing in the Mediterranean area. The structures have been elucidated on the basis of their spectroscopic properties. Bidimensional NMR (DQ- COSY, TOCSY, NOESY, ROESY, HSQC, and HMBC) furnished important data useful for the characterization of the molecules. The compounds have been assayed, for the antioxidant activity, by measuring its capacity to scavenge the DPPH, the superoxide anion, and nitric oxide radicals. Ó 2006 Elsevier Ltd. All rights reserved. Many diseases are caused by oxidative stress. Accelerat- ed cell oxidation contributes to cardiovascular disease, tumor growth, wrinkled skin, cancer, Alzheimer’s dis- ease, and even a decline in energy and endurance. 1–4 Vitamins A, C, and E are the antioxidant food vitamins. They inhibit the oxidation process, or chemical reac- tions, that occurs during the development of coronary heart disease and some cancers, which means these vita- mins may also help with the prevention of these diseases. In the search for new antioxidant metabolites from nat- ural sources we studied some plants living in the Medi- terranean area, and many new bioactive metabolites have been isolated and characterized. 5 Recently 6 we reported the structural elucidation and the antioxidant activity of the distachyasin, a novel antioxidant preny- lated stilbenoid isolated from the leaves of Carex distachya. 7 In this article, we report the isolation and the structural elucidation of two new dibenzoxazepinones. 8 The EI mass spectrum of compound 1 9 showed a molec- ular ion at m/z 315 which, together with the elemental analysis, defined the molecular formula as C 17 H 17 NO 5 . The IR spectrum showed an intense band at 1619 cm À1 , besides other medium bands at 3702, 3601, and 1582 (see Fig. 1). The 1 H NMR spectrum (Table 1) showed three aromatic protons as a singlet at d 6.93 and two doublets at d 6.83 and 6.42, two methoxyl groups at d 3.97 and 3.81, two methyls at d 2.19 and 2.12, and a singlet at d 8.07. All the proton signals were assigned to the correspond- ing carbons through direct 1 H– 13 C correlations in the HSQC (Table 1) spectrum, with exception of the singlet at d 8.07, which value was in good accordance with a proton of an amidic group. The 13 C NMR spectrum showed 17 carbon signals, identified on the basis of the DEPT experiment as four 0960-894X/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.bmcl.2006.11.002 Keywords: Dibenzoxazepinones; Carex distachya; Spectroscopic anal- ysis; Radical scavenging activity. * Corresponding author. Tel. +39 823274576; fax: +39 823274571; e-mail: antonio.fiorentino@unina2.it O HN O HO O 1 4 8 9a 11 5a 4a 1a 6 OR 1 R 1 2 R = R 1 = Me R = R 1 =H Figure 1. Chemical structures of dibenzoxazepinones from C. distachya. Bioorganic & Medicinal Chemistry Letters 17 (2007) 636–639