Third-party-funded project
Title:
"Naphthylisoquinoline Alkaloids: Biological Activity, Biogenesis, and Metabolism" within the Center Grant (Sonderforschungsbereich 251) "Ecology, Physiology, and Biochemistry of Plants and Animals under Stress"
Project management at the University of Würzburg:
Participating scientists:
- Prof. Dr. Peter Proksch
, Institut für Pharmazeutische Biologie der Universität Düsseldorf
- Dr. Michael R. Boyd
, US National Cancer Institute, Frederick, USA
- Dr. Reto Brun
, Schweizerisches Tropeninstitut, Basel
- Prof. Dr. Virima Mudogo
, Université de Kinshasha, Republik Kongo
- Prof. Dr. Laurent Aké Assi
, Cente National de Floristique, Abidjan, Elfenbeinküste
- Dr. Jan Schlauer
- Dr. Michael Wohlfarth
- Dr. Heiko Rischer
- Dr. Kristina Wolf
- Dr. Matthias Wenzel
- Dr. Friedrich Teltschik
- Dr. Jörg Mühlbacher
- Dr. Michael Ochse
- Dr. Wael Saeb
- Dr. Christian Günther
Abstract:
The naphthylisoquinoline alkaloid dioncophylline A, one of the most prominent representatives of a new class of intriguing secondary metabolites, was shown to originate from acetate units, both molecular halves, the isoquinoline part and the naphthalene portion, being formed from identical polyketide precursors. All other tetrahydroisoquinoline alkaloids previously investigated, ultimately originate from aromatic amino acids. The novel pathway to isoquinoline alkaloids (hence acetogenic) was proved by feeding experiments with 13C2-labelled precursors administered to callus cultures of Triphyophyllum peltatum (Dioncophyllaceae), followed by NMR investigations (2D INADEQUATE experiments for the identifcation of direct C-C connectivities) using the potent cryoprobe methodology. The new pathway is largely stress-sensitive: upon exposure to chemical, biotic or physical stress, T. peltatum stops producing the isoquinoline part, so that the napthalene moiety accumulates in the chemical form of naphthoquinones like plumbagin and droserone and the chiral tetralone isoshinanolone.
Key words:
Dioncophylline A
Polyketide Metabolism
Naphthylisoquinoline Alkaloids
Dioncophyllaceae
Plant Stress
Acetogenic Biosynthesis
Isoquinoline Alkaloids
Projekt period:
from 01.1998 to 12.2000
Funding institution:
DFG ( SFB 251, vierte Förderperiode )
Preceding project:
SFB 251, dritte Förderperiode
Publications:
- G. Bringmann, H. Rischer.
(2001). In vitro propagation of the alkaloid-producing rare African liana, Triphyophyllum peltatum (Dioncophyllaceae). (monograph)
- G. Bringmann, D. Feineis.
(2001). Stress-related polyketide metabolism of Dioncophyllaceae and Ancistrocladaceae. (monograph)
- G. Bringmann, M. Wohlfarth, H. Rischer, M. Heubes, W. Saeb, S. Diem, M. Herderich, J. Schlauer.
(2001). A Photometric Screening Method for Dimeric Naphthylisoquinoline Alkaloids and Complete On-Line Structural Elucidation of a Dimer in Crude Plant Extracts, by the LC-MS/LC-NMR/LC-CD Triad. (monograph)
- M. Dreyer, B.W. Nugroho, F.I. Bohnenstengel, R. Ebel, V. Wray, L. Witte, G. Bringmann, J. Mühlbacher, M. Herold, P.D. Hung, L.C. Kiet, P. Proksch.
(2001). New Insecticidal Rocaglamide Derivatives and Related Compounds from Aglaia oligophylla. (monograph)
- G. Bringmann, M. Wenzel, H.P. Bringmann, J. Schlauer, L. Aké Assi, F. Haas.
(2001). Uptake of the Amino Acid Alanine by Digestive Leaves: Proof of Carnivory in the Tropical Liana Triphyophyllum peltatum (Dioncophyllaceae). (monograph)
- G. Bringmann, K. Messer, W. Saeb, E.-M. Peters, K. Peters.
(2001). The absolute configuration of (+)-isoshinanolone and in situ LC-CD analysis of its stereoisomers from crude extracts. Phytochemistry 56: 387-391, (scientific article)
- G. Bringmann, A. Hamm, C. Günther, M. Michel, R. Brun, V. Mudogo.
(2000). Ancistroealaines A and B, Two New Bioactive Naphthylisoquinolines, and Related Naphthoic Acids from Ancistrocladus ealaensis. J. Nat. Prod. 63: 1465-1470, (scientific article)
- G. Bringmann, C. Günther, W. Saeb, J. Mies, A. Wickramasinghe, V. Mudogo, R. Brun.
(2000). Ancistrolikokines A-C: New 5,8'-Coupled Naphthylisoquinoline Alkaloids from Ancistrocladus likoko. J. Nat. Prod. 63: 1333-1337, (scientific article)
- G. Bringmann, D. Feineis.
(2000). Novel Antiparasitic Biaryl Alkaloids from Westafrican Dioncophyllaceae Plants. Act. Chim. Thérapeut. 26: 151-171, (scientific article)
- G. Bringmann, C. Günther, W. Saeb, J. Mies, R. Brun, L. Aké Assi.
(2000). 8-O-Methyldioncophyllinol B and Revised Structures of Other 7,6'-Coupled Naphthylisoquinoline Alkaloids from Triphyophyllum peltatum (Dioncophyllaceae). Phytochemistry 54: 337-346, (scientific article)
- G. Bringmann, H. Rischer, M. Wohlfarth, J. Schlauer, L. Aké Assi.
(2000). Droserone from Cell Cultures of Triphyophyllum peltatum (Dioncophyllaceae) and its Biosynthetic Origin. Phytochemistry 53: 339-343, (scientific article)
- G. Bringmann, M. Wohlfarth, H. Rischer, J. Schlauer.
(2000). Ein neuer Biosyntheseweg zu Alkaloiden in Pflanzen: acetogenine Isochinoline. - A New Biosynthetic Pathway to Alkaloids in Plants: Acetogenic Isoquinolines. Angew. Chem. 112: 1523-1525; Angew. Chem. Int. Ed. Engl. 39: 1464-1466, (scientific article)
- G. Bringmann, H. Rischer, J. Schlauer, L. Aké Assi.
(1999). In vitro propagation of Ancistrocladus abbreviatus Airy Shaw (Ancistrocladaceae). Plant Cell Tiss. Org. Cult. 57: 71-73, (scientific article)
- G.Bringmann, J. Schlauer, M. Rückert, B. Wiesen, K. Ehrenfeld, P. Proksch, F.-C. Czygan.
(1999). Host-Derived Acetogenins Involved in the Incompatible Parasitic Relationship between Cuscuta reflexa (Convolvulaceae) and Ancistrocladus heyneanus (Ancistrocladaceae). Plant Biol. 1: 581-584, (scientific article)
- G. Bringmann, J. Holenz, W. Saeb, L. Aké Assi, K. Hostettmann.
(1999). Dioncophylline A as a Larvicide against Aedes aegypti. Pharm. Pharmacol. Lett. 9: 24-25, (scientific article)
- G. Bringmann, F. Teltschik, M. Michel, S. Busemann, M. Rückert, R. Haller, S. Bär, S.A. Robertson, R. Kaminsky.
(1999). Ancistrobertsonines B, C, and D as well as 1,2-didehydroancistrobertsonine D from Ancistrocladus robertsoniorum. Phytochemistry 52: 321-332, (scientific article)
- G. Bringmann, K. Messer, M. Wohlfarth, J. Kraus, K. Dumbuya, M. Rückert.
(1999). HPLC-CD On-Line Coupling in Combination with HPLC-NMR and HPLC-MS/MS for the Determination of the Full Absolute Stereostructure of New Metabolites in Plant Extracts. Anal. Chem. 71: 2678-2686, (scientific article)
- G. Bringmann, M. Münchbach, K. Messer, D. Koppler, M. Michel, O. Schupp, M. Wenzel, A.M. Louis.
(1999). Cis- and trans-Isoshinanolone from Dioncophyllum thollonii: absolute configuration of two 'known', wide-spread natural products. Phytochemistry 51: 693-699, (scientific article)
- B.W. Nugroho, R.A. Edrada, V. Wray, L. Witte, G. Bringmann, M. Gehling, P. Proksch.
(1999). Insecticidal Rocaglamide Derivatives and Related Compounds from Aglaia odorata (Meliaceae). Phytochemistry 51: 367-376, (scientific article)
- G. Bringmann, J. Schlauer, K. Wolf, H. Rischer, U. Buschbom, A. Kreiner, F. Thiele, M. Duschek, L. Aké Assi.
(1999). Cultivation of Triphyophyllum peltatum (Dioncophyllaceae), the Part-Time Carnivorous Plant. Carniv. Pl. Newslett. 28: 7-13, (scientific article)
- G. Bringmann, M. Rückert, K. Messer, O. Schupp, A.M. Louis.
(1999). Use of on-line high-performance liquid chromatography - nuclear magnetic resonance spectrometry coupling in phytochemical screening studies: rapid identification of metabolites in Dioncophyllum thollonii. J. Chromatogr. A 837: 267-272, (scientific article)
- G. Bringmann, M. Rückert, W. Saeb, V. Mudogo.
(1999). Characterization of Metabolites in Plant Extracts of Ancistrocladus likoko by High-Performance Liquid Chromatography Coupled on-line with 1H NMR Spectroscopy. Magn. Res. Chem. 37: 98-102, (scientific article)
- G. Bringmann, M. Wenzel, T.R. Kelly, M.R. Boyd, R.J. Gulakowski, R. Kaminsky.
(1999). Octadehydromichellamine, a Structural Analog of the Anti-HIV Michellamines without Centrochirality. Tetrahedron 55: 1731-1740, (scientific article)
Links:
Research Group Prof. Bringmann - Homepage
