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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.

Two novel cyclic tridecapeptides, tolybyssidins A (1) and B (2), were isolated from the culture medium of mass cultured cyanobacterium Tolypothrix byssoidea (EAWAG 195) by means of bioguided isolation. The gross structures of these peptides were determined by 1D and 2D NMR experiments and tandem mass spectrometry. Both peptides contain the nonnatural amino acid dehydrohomoalanine (Dhha) as well as proteinogenic amino acids albeit with d- or l-configuration. The compounds exhibit moderate antifungal activity against the yeast Candida albicans.

The physiological substance and precursor of the heme synthesis 5‐aminolevulinic acid (ALA) is a promising prodrug for photodiagnosis and photodynamic therapy of epithelial tumors, particularly in urological and gynecological tissues. For the clinical use of this substance, a chemically stable and sterile drug formulation is required. In the present study, degradation mechanism of ALA in aqueous solution and possibilities to improve its stability were examined. A capillary electrophoretic method was developed that was suitable for the quantification of ALA and of two degradation products. The intermediate degradation product was 2,5‐dicarboxyethyl‐3,6‐dihydropyrazine, which was further oxidized to 2,5‐dicarboxyethylpyrazine. The structures of the degradation products were proven by 1H and 13C nuclear magnetic resonance spectroscopy. ALA degradation was very efficiently inhibited by adjusting the pH of the aqueous solution to a value <5 and by purging with nitrogen. Additives such as antioxidants did not improve the ALA stability. These results demonstrated that low pH ALA aqueous solution may be one possible dosage form to be considered for market introduction. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1335–1341, 2000

The physiological substance and precursor of the heme synthesis 5-aminolevulinic acid (ALA) is a promising prodrug for photodiagnosis and photodynamic therapy of epithelial tumors, particularly in urological and gynecological tissues. For the clinical use of this substance, a chemically stable and sterile drug formulation is required. In the present study, degradation mechanism of ALA in aqueous solution and possibilities to improve its stability were examined. A capillary electrophoretic method was developed that was suitable for the quantification of ALA and of two degradation products. The intermediate degradation product was 2,5-dicarboxyethyl-3,6-dihydropyrazine, which was further oxidized to 2,5-dicarboxyethylpyrazine. The structures of the degradation products were proven by ¹H and ¹³C nuclear magnetic resonance spectroscopy. ALA degradation was very efficiently inhibited by adjusting the pH of the aqueous solution to a value &lt;5 and by purging with nitrogen. Additives such as antioxidants did not improve the ALA stability. These results demonstrated that low pH ALA aqueous solution may be one possible dosage form to be considered for market introduction. © 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1335–1341, 2000

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)-5β-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)-5β-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)-5β-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.

Two new iridoid glucosides, 6-O-acetylajugol (1) and 7,8-epoxy-8-epi-loganic acid (2), together with five known iridoid glucosides, galiridoside (3), ajugoside (4), 10-deoxygeniposidic acid (5), 7-deoxy-8-epi-loganic acid (6), and 8-O-acetylharpagide (7), have been isolated from the aerial parts of Leonurus persicus. Leucosceptoside A (8), eugenyl β-rutinoside (9), and kaempferol 3-O-glucoside (10) were also isolated. The structures of 1 and 2 were elucidated by extensive 1D- and 2D-NMR spectroscopy and molecular modeling. The structure of 3 was confirmed by single-crystal X-ray diffraction. Antimicrobial activity of compounds (1−10) was also evaluated against a panel of Gram-positive and Gram-negative bacteria and two strains of fungi.

The randomization analysis of a randomized blocks design is extended to the situation where the observations are growth (or response) curves. A randomization test is developed for testing treatment effects over time (or stimulus) intervals pre-specified by the investigator.

The multiplet structure of cross peaks in double-quantum-filtered COSY NMR spectra is analysed for those resonances that include passive heteronuclear couplings. Interestingly, the cross peak involving the sugar-ring protons H2' and H3' in nucleic acids display an E.COSY-type appearance exclusively when the backbone torsion angle ? (C4'-C3'-O3'-P) adopts a gauche(-) conformation. This observation allows an unambiguous analysis of the conformation around ?, without the knowledge of 3Jcp coupling constants.

A novel cycloartane-type glycoside, cyclocephaloside I (1) was isolated from the roots of Astragalus microcephalus in addition to known glycosides cyclocanthoside E (2) and astragaloside IV (3). The structure of 1 was determined by spectral (IR, ¹H and ¹³C NMR, and FABMS) and chemical (acetylation) methods and established as 20,25-epoxy-3β-(β-d-xylopyranosyl)oxy-6α-(β-d-glucopyranosyl)oxy-cycloartane-16β,24α-diol.