New Eremophilane Sesquiterpenes from a Rhizome Extract of Petasites hybridus by Antje Bodensieck, Olaf Kunert, Ernst Haslinger, and Rudolf Bauer* Institute of Pharmaceutical Sciences, Karl-Franzens University of Graz, A-8010 Graz (phone: + 43-316-380-8700; fax: + 43-316-380-9860; e-mail: rudolf.bauer@uni-graz.at) A total of 21 natural products, 1 – 21, were isolated from a supercritical CO 2 extract of the rhizomes of Petasites hybridus . Thereby, seven new eremophilane (= (1S,4aR,7R,8aR)-decahydro-1,8a-dimethyl-7- (1-methylethyl)naphthalene) sesquiterpenes, compounds 4, 5, 9, 11, 12, 15, and 17, were identified. The new constituent 9-hydroxyisobakkenolide (15) is the first representative of a group of compounds closely related to the well-known, but rare, bakkenolides. Tsoongianolide B (18) and its degradation product lig- ularenolide (19) were found as new Petasites constituents as well. The known eremophilanolide 2 was iso- lated from a plant source for the first time and the oxofuranopetasin 16 was isolated for the first time from the rhizomes of P. hybridus , together with eight other known compounds. The C(8)-epimeric 2- [(tigloyl)oxy]eremophilanolides 3 and 8 could clearly be differentiated. All structures were established by extensive 1D- and 2D-NMR experiments (Tables1–3), and confirmed by in-depth GC/MS and HPLC/MS experiments. Introduction. – Petasites hybridus (L.) GAERTN., MEY .etSCHERB. (Asteraceae, tribe Senecioneae) is native to Europe and Northwest Asia, and has been introduced to North America. Characteristic features are a strange, aromatic smell and short, bulbous rhizomes. Meter-long runners allow the formation of big colonies. P. hybridus (but- terbur) is traditionally used against spasms of the gastrointestinal tract, headache, dis- eases of the respiratory tract, and externally for support of wound healing and against malignant ulcers [1]. Modern pharmacological investigations started with Bucher)s experiments concerning the antispasmodic activity of P. hybridus extracts in isolated guinea pig bowels [2]. Perennial allergic rhinitis and the preventive treatment of migraine are more-recent indications for butterbur extracts [3][4]. In the mid-1950s, two Swiss groups isolated sesquiterpenes of the eremophilane type from butterbur rhizomes for the first time [5][6]. Novotny ´ et al. [7] described a petasin and a furan-chemovar of butterbur. The furanoeremophilanes of the latter are predominantly oxidized at C(9), less frequently at C(3), and often at both C(2) and C(9) [8]. In the course of our ongoing investigations concerning the anti-inflamma- tory activities of P. hybridus , we found that COX-2 inhibition is independent of the petasin content [9]. Therefore, we focused our investigations on a commercial CO 2 (spissum) extract of subterranean plant material belonging to the furan-chemovar type, which is rich in furanoeremophilanes and their transformation products, eremo- philane lactones. # 2007 Verlag Helvetica Chimica Acta AG, Zürich Helvetica Chimica Acta – Vol. 90 (2007) 183