Expanding the “Terpenome” by Chemoenzymatic Telescoping, Cyclisation and Oxidation of Synthetic FPP Analogues

Terpenes constitute the largest class of natural products with a broad structural diversity and biological activity. Their industrial applications span from small representatives like menthol used in fragrance industry, to structurally more diverse natural products like taxol in pharmaceutical industry. To achieve this diversity, formation of stereo dense carbon skeletons from simple linear precursors catalysed by terpene synthases is crucial. These enzymes have been investigated regarding their mode of action, substrate promiscuity and in this context their potential as biocatalysts using synthetic FPP analogues. As they have proven to be very versatile, they offer access to new terpenoids. Following the cyclisation towards carbon scaffolds, enzymatic oxidation in terpene biosynthesis enables further functionalisation and diversification. Since the oxyfunctionalisation of non-activated CH-groups is a challenging area in synthetic organic chemistry, sustainable enzymatic solutions are of high academic and industrial interest. Unspecific peroxygenases, a fungal class of haem dependent enzymes, could serve as a scalable biotechnological solution in organic synthesis. In this thesis, the chemical synthesis of new and known FPP analogues, their enzymatic telescoping, cyclisation and oxidation are presented. New sesqui- and diterpenoids were formed and isolated through biotransformation with those analogues. Structure elucidation of new terpenoids was performed mainly based on NMR spectroscopy. These results were used to understand the promiscuity of terpene synthases and the influence of derivatisation on cyclisation cascades. Furthermore, the oxidation of non-natural terpenoids by unspecific peroxygenases was investigated.