Biogenesis of axially chiral biaryl alkaloids from plants

GERHARD BRINGMANN
Institut für Organische Chemie der Universität
Am Hubland
D-97074 Würzburg
bringman@chemie.uni-wuerzburg.de
http://www-organik.chemie.uni-wuerzburg.de/

This interdisciplinary project (Natural Product Chemistry - Plant Molecular Biology and Biochemistry) comprises two research issues. The first topic deals with the unprecedented biosynthesis of the axially chiral naphthylisoquinoline alkaloids. We have shown that both molecular halves, the isoquinoline part and the naphthalene portion, are formed from identical polyketide precursors. Besides the search for biosynthetic precursors of the alkaloids (including molecular halves and biosynthetic intermediates) in Ancistrocladaceae and Dioncophyllaceae plants by applying modern hyphenated techniques (i.a., LC-NMR, LC-MS/MS, and LC-CD), the project mainly deals with the elucidation of key steps and the characterization of the respective enyzmes involved in the construction of the unusual carbon skeleton of these acetogenic alkaloids. The following objectives are in the scope of the project:

(1) Development of synthetic pathways to postulated intermediates (e.g., to open-chain polyketones, monocyclic diketones, the free bicyclic isoquinoline and naphthalene moieties, primary coupling products) and search for them in the plants and in cell cultures.

(2) Synthesis of ¹³C and/or ¹⁵N labeled compounds for biosynthetic feeding experiments to probe their identity as authentic biosynthetic precursors. The second project deals with the axially chiral biscarbazole alkaloids from Rutaceae plants and with their biosynthetic origin from indol or tryptophan involving a prenylation at C-2 and oxidative ring closure, followed by phenol-oxidative coupling to give the intact dimeric alkaloids. In close cooperation with the research group of Prof. Li (University of Düsseldorf) it is planned to isolate, purify, and characterize the enzymes involved in the prenylation step of carbazole alkaloid biogenesis. The planned comparison between plant- and bacteria-derived prenyltransferases will make it possible to gain insight into the diversity of prenylated natural products (secondary metabolites).

[back]