Novel Natural Products from Medicinal Plants

1. Key Words:

Bioassay-guided search for new lead structures from African and Asian plants used in folk medicine; fields of indications: i.a., antifungal, antimalarial, antileishmanial, antitrypanosomal, antiviral actitivity (see also 'Naphthylisoquinoline Alkaloids'); metabolic profiling using our novel 'triad' : LC coupled to NMR, MS/MS, and CD (see also 'Natural Product Analysis'); isolation and structural elucidation: i.a., by chromatographical, spectroscopic, chemical, and theoretical methods (see also 'Computational Chemistry'); cultivation of plants and plant tissue cultures; investigations on the biogenesis of novel-type compounds by feeding experiments.

2. Graphical Abstract:

Subtopic A: Selected Bioactive Compounds from Tropical Plants

Figure 1: Novel natural products from tropical plants [1,2,3,4,5]

Subtopic B: Elucidation of the Biosynthetic Origin of Natural Products

Figure 2: A novel type of glycine-derived acetogenic quinoline alkaloids: antidesmone from the East-African shrub Antidesma membranaceum [6,7]

Figure 3: The polyketide folding mode in the biogenesis of cis-isoshinanolone from Ancistrocladus heyneanus [8]

3. Brief Description:

Higher plants, in particular those 'pre-selected' by the traditional healers of the respective countries, constitute a rewarding source of novel bioactive natural products. Plants selected by ethnobotanical criteria, are investigated for the biological activities of their extracts, the active compounds are isolated, and their structures established (see Figure 1) [1,2,3,4,5]. Among the fields of indication are herbicidal, fungicidal, antitumor, CNS, and antihypertensive activities (test systems established by the BASF AG) as well as antiparasitic (e.g., 'antimalarial'), antileishmanial, antitrypanosomal) activities (test systems established by the Swiss Tropical Institute, Basel, Switzerland). Furthermore, our interest is focused on the elucidation of the biosynthetic origin of natural products. As an example, key hints at the correct structure of antidesmone, a novel-type quinoline alkaloid from the East African medical plant Antidesma membranaceum (Euphorbiaceae) [6], were obtained from an investigation of the biogenesis of this unusual novel alkaloid, which is built up mainly from acetate units; the nitrogen-containing part, however, originates from glycine, showing antidesmone to belong to a biosynthetically novel type of glycine-derived alkaloids [7] (see Figure 2). Fully acetogenic, by contrast, is cis-isoshinanolone [8], a wide-spread tetralone, e.g., from the Indian liana Ancistrocladus heyneanus (see Figure 3) and other species of Ancistrocladaceae and Dioncophyllaceae [4,5]. Feeding experiments revealed the complete mode of folding of the intermediate polyketide chain.

4. Selected Publications:

[1]	G. Bringmann, M. Ochse, K. Wolf, J. Kraus, K. Peters, E.-M. Peters, M. Herderich, L. Aké Assi, F.K. Tayman; 4-Oxonicotinamide-1-(1'-ß-d-ribofuranoside) from Rothmannia longiflora Salisb. (Rubiaceae); Phytochemistry 1999, 51, 271-276.
[2]	G. Bringmann, A. Hamm, J. Kraus, M. Ochse, A. Noureldeen, D. Jumbam; Gardenamide A from Rothmannia urcelliformis (Rubiaceae) - Isolation, Absolute Stereostructure, and Biomimetic Synthesis from Genipine; Eur. J. Org. Chem. 2001, 1983-1987.
[3]	G. Bringmann, G. François, L. Aké Assi, J. Schlauer; The Alkaloids of Triphyophyllum peltatum (Dioncophyllaceae); Chimia 1998, 52, 18-28.
[4]	G. Bringmann, M. Wohlfarth, H. Rischer, M. Rückert, J. Schlauer; The Polyketide Folding Mode in the Biogenesis of Isoshinanolone and Plumbagin in Ancistrocladus heyneanus (Ancistrocladaceae); Tetrahedron Lett. 1998, 39, 8445-8448.
[5]	G. Bringmann, M. Münchbach, K. Messer, D. Koppler, M. Michel, O. Schupp, M. Wenzel, A.M. Louis; Cis- and trans- isoshinanolone from Dioncophyllum thollonii: absolute configuration of two 'known', wide-spread natural products; Phytochemistry 1999, 51, 693-699.
[6]	G. Bringmann, K. Messer, W. Saeb, E.-M. Peters, K. Peters; The absolute configuration of (+)-isoshinanolone and in situ LC-CD analysis of its stereoisomers from crude extracts; Phytochemistry 2001, 56, 387-391.
[7]	G. Bringmann, J. Schlauer, H. Rischer, M. Wohlfarth, J. Mühlbacher, A. Buske, A. Porzel, J. Schmidt, G. Adam; Revised Structure of Antidesmone, an Unusual Alkaloid from Tropical Antidesma Plants (Euphorbiaceae); Tetrahedron 2000, 56, 3691-3695.
[8]	G. Bringmann, H. Rischer, M. Wohlfarth, J. Schlauer; Biosynthesis of Antidesmone in Cell Cultures of Antidesma membranaceum (Euphorbiaceae): An Unprecedented Class of Glycine-Derived Alkaloids; J. Am. Chem. Soc. 2000, 122, 9905-9910.