Abietic acid (1) and its methyl ester (2) were investigated under various storage conditions to provide an indication of their preferred oxidation mechanisms and to investigate the most susceptible positions for modification in the abietane skeleton. Six known compounds, methyl 7alpha,13beta-dihydroxyabiet-8(14)-enoate (4a), methyl 7alpha,13alpha-dihydroxyabiet-8(14)-enoate (4b), methyl 12-oxoabietate (6), methyl 7-oxodehydroabietate (7), methyl 7alpha-hydroxydehydroabietate (8), and 13,14-seco-13,14-dioxoabiet-7(8)-enoic acid (11), were identified. Compounds 7 and 8 are regarded as potent allergens. In addition, six new oxidation products were isolated, methyl 13beta-ethoxy-7alpha-hydroxyabiet-8(14)-enoate (3a), methyl 13alpha-ethoxy-7alpha-hydroxyabiet-8(14)-enoate (3b), methyl 7alpha-hydroperoxy-13alpha-hydroxyabiet-8(14)-enoate or methyl 13alpha-hydroperoxy-7alpha-hydroxyabiet-8(14)-enoate (5), 7alpha,13beta-dihydroxyabiet-8(14)-enoic acid (9a), 7alpha,13alpha-dihydroxyabiet-8(14)-enoic acid (9b), and 7alpha,15-dihydroxydeydroabietic acid (10). Their structures were characterized on the basis of spectroscopic data interpretation. The cytotoxicity of several compounds against KB cells was evaluated, and weak activity was observed for 6, 7, and 8 with IC(50) values of 12.5, 4.5, and 5.8 microg/mL, respectively.

Five new prenylated tricyclic and three new bicyclic acylphloroglucinol derivatives have been isolated by bioactivity-guided fractionation of the petroleum ether extract of the dried aerial parts of Hypericum papuanum. The tricyclic compounds (1--5) were named papuaforins A--E. The bicyclic compounds were isolated together with their corresponding tautomers and were named hyperguinones A and B (6/6a,7/7a) and hyperpapuanone (8/8a), respectively. Their structures were elucidated on the basis of extensive 1D and 2D NMR experiments, as well as mass spectrometry. Furthermore, the cytotoxicity toward KB nasopharyngeal carcinoma cells and the antibacterial activity of the isolated compounds were determined.

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)-5beta -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)-5beta-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)-5beta-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.

Twenty-one phloroglucinol derivatives, belonging to 8 different carbon skeletons, were tested for their ability to influence the oxidative burst of polymorphonuclear cells (PMNs) after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan (OZ). Results revealed a strong reduction of oxygen production by PMNs after stimulation with FMLP for the compounds ialibinone E ( 5), hyperguinone B ( 15) and hyperforin ( 21). The IC 50 values obtained were 2.5 microM ( 5), 3.3 microM ( 15) and 1.8 microM ( 21), respectively. Slight modifications of the substituents or variation of the stereochemistry resulted in a significant loss of activity. None of the active compounds showed antioxidative activity after stimulation with OZ. The influence of compounds 5, 15 and 21 on the production of oxygen radicals in an H 2 O 2 /horseradish peroxidase system was investigated and revealed potent activity only for compound 5 (IC 50 1 microM). The superoxide-scavenging properties of ialibinone E ( 5) and hyperguinone B ( 15) were additionally tested in a cytochrome c assay and only ialibinone E ( 5) was found to be significantly active at lower micromolar concentrations. Ialibinone E ( 5) was not active in a xanthine oxidase assay (urate formation) in concentrations up to 100 microM and its activity is therefore not attributable to the inhibition of this enzyme. It can be assumed that the activity of compounds 5 and 15 in the different cellular and enzymatic assays, is most likely caused by different and maybe specific mechanisms and cannot be explained by a radical scavenger activity alone. None of the active phloroglucinols showed cytotoxic effects against the PMNs.