New Phloroglucinol Derivatives from Hypericum papuanum Karin Winkelmann, † Jo ¨rg Heilmann, † Oliver Zerbe, † Topul Rali, ‡ and Otto Sticher* ,† Department of Pharmacy, Swiss Federal Institute of Technology (ETH) Zurich, CH-8057 Zu ¨ rich, Switzerland, and PNG Biodiversity Research PTY Ltd., Port Moresby, Papua New Guinea Received August 25, 1999 Bioactivity-guided fractionation of the petroleum ether extract of the aerial parts of Hypericum papuanum led to the isolation of five new tricyclic phloroglucinol derivatives. On the basis of extensive 1D and 2D NMR experiments as well as MS studies, their structures were elucidated as the C-3 epimers of 8-hydroxy- 4,4,7-trimethyl-9-(2-methylpropionyl)-3-(1-methylvinyl)-5-H-tricyclo[5.3.1.0 1,5 ]undec-8-ene-10,11-dione (1, 2); the C-3 epimers of 8-hydroxy-4,4,7-trimethyl-9-(2-methylbutyryl)-3-(1-methylvinyl)-5-H-tricyclo- [5.3.1.0 1,5 ]undec-8-ene-10,11-dione (3, 4), and 8-hydroxy-4,4,7-trimethyl-9-(2-methylpropionyl)-5-H- tricyclo[5.3.1.0 1,5 ]undec-8-ene-10,11-dione (5), and their corresponding tautomers (1a, 2a, 3a, 4a, 5a). Compounds 1/1a-5/5a were named ialibinones A-E, respectively. Compounds 1/1a-4/4a showed antibacterial activity against Bacillus cereus, Staphylococcus epidermidis, and Micrococcus luteus. The leaves of Hypericum papuanum Ridley (Guttiferae), a shrub or woody herb widespread in all mountainous regions of New Guinea, 1 are used in folk medicine for the treatment of sores. 2 In the genus Hypericum many phlo- roglucinol derivatives with antibiotic properties have been isolated, of which some are derivatives of the well-known hyperforin, isolated from Hypericum perforatum L., while others are phloroglucinol derivatives with filicinic acid moieties. 3-5 Bioactivity-guided fractionation of the petro- leum ether extract of the aerial parts of H. papuanum has led to the isolation of five new phloroglucinol derivatives with tricyclic structures (1/1a-5/5a), four of which are active against Bacillus cereus, Staphylococcus epidermidis, and Micrococcus luteus. No reports concerning the isolation of similar tricyclic phloroglucinol derivatives from the family Guttiferae have appeared in the literature so far. However, structurally related semisynthetic transforma- tion products of the hop constituents humulone and colu- pulone obtained by oxidation and isomerization have been described. 6,7 In addition, the isolation of aissatone from Harrisonia abyssinica Oliv. (Simaroubaceae) was published recently. 8 Results and Discussion The air-dried aerial parts of H. papuanum were ex- tracted successively with petroleum ether, dichloromethane, methanol, and methanol-water mixtures. The petroleum ether extract showed antibacterial activity against B. cereus, S. epidermidis, and M. luteus and was therefore subjected to repeated vacuum-liquid chromatography (VLC) and HPLC, which led to the isolation of five new phloroglucinol derivatives (1/1a-5/5a). All five compounds were isolated as yellow oils. After being sprayed with vanillin-sulfuric acid reagent, 9 the substances gave tur- quoise spots by TLC. The 1 H NMR spectrum of 1/1a revealed the presence of 12 methyl groups, eight of which are tertiary (δ H 0.85, 0.88, 0.99, 1.00, 1.35, 1.41, 1.78, 1.79, each s) and four secondary (δ H 1.13, d, J ) 6.8 Hz; 1.17, d, J ) 6.8 Hz; 1.17, d, J ) 6.8 Hz; 1.22, d, J ) 6.8 Hz), as well as two septets indicative of methines in a 2-methylpropionyl side chain (δ H 3.96, sept, J ) 6.8 Hz; 4.03, sept, J ) 6.8 Hz). Furthermore, four signals indicating terminal methylenes (δ H 4.79, 4.81, 4.94, 4.95, each br s) could be detected in addition to a number of overlapping aliphatic signals in the range of 2.0 to 2.6 ppm. The unusually lowfield shifted signals (δ H 18.43, 18.75, each br s) suggested the presence of hydroxyl protons that participate in rather strong hydrogen bonds (for 1 H NMR data, see Tables 1 and 2). The 13 C NMR showed signals of 42 carbons, which could be sorted by DEPT experiments into 12 methyl, six meth- * To whom correspondence should be addressed. Tel.: +41 1 635 6050. Fax: +41 1 635 6882. E-mail: sticher@pharma.ethz.ch. † Swiss Federal Institute of Technology (ETH) Zurich. ‡ PNG Biodiversity PTY, Ltd. 104 J. Nat. Prod. 2000, 63, 104-108 10.1021/np990417m CCC: $19.00 © 2000 American Chemical Society and American Society of Pharmacognosy Published on Web 12/11/1999