Studies on the Biosynthesis and Structure Elucidation of Terpene Natural Products by Isotopic Labeling Experiments

Abstract

The cumulative doctoral thesis "Studies on the Biosynthesis and Structure Elucidation of Terpene Natural Products by Isotopic Labeling Experiments" deals with the application of stable isotopes for structure elucidation and biosynthesis studies of terpenoids from microorganisms. Additionally, analytic and synthetic studies on volatile natural products were conducted.<br /> A highly sensitive method for the identification of terpenes from fungal organisms, based on in vivo incorporation of 13C-labeled biosynthetic precursors was developed. This method was successfully applied for the identification of pogostol from the endophytic fungus Geniculosporium, of harzianone from the biocontrol fungus Trichoderma and of hypodoratoxide from the mycophilic fungus Hypomyces odoratus. The results gave additional insights into the biosynthesis of these metabolites. Isotopically labeled substrates were also designed, synthesized and utilized for in vitro experiments with recombinant enzymes from bacterial sources.<br /> Additionally, two studies on volatile metabolites from microorganisms were conducted. Nineteen recently genome sequenced actinomycetes were investigated and the chemical analysis was correlated to genome sequencing data. The volatiles of five sponge-associated fungi were analyzed and a series of bioactive metabolites, like the quorum sensing inhibitor protoanemonin, a highly phytotoxic lactone and algicidal phloroglucinol derivates were identified.<br /> During studies towards the total synthesis of the sesquiterpene koraiol, an enantioselective approach for the synthesis of a pseudosymmetric, tetrasubstituted all-trans cyclobutane was developed. The method makes use of a chiral auxiliary in a diastereoselective photodimerization. The obtained cyclobutane derivative is a key intermediate in the total synthesis of the highly bioactive sponge-derived metabolite sceptrin.