This thesis aimed at the total synthesis of five natural products belonging to the classes of terpenoids, polyketides and meroterpenoids. The first project describes a short total synthesis of the C11-homoterpenoid (+)-Greek tobacco lactone, an oxidative degradation product that was isolated from the sun-cured leaves of Greek tobacco. The natural product is characterised by a cis-fused tetrahydropyran-butyrolactone scaffold. In order to develop an efficient synthetic route, various concepts of synthesis economy were used as guidelines. The identification of (R)-linalool, an abundant and renewable chiral pool C10-feedstock, as the starting material enabled the rapid construction of the carbon scaffold including the first stereocenter. Key steps of the synthesis are two strategic oxidations of the double bonds present in (R)-linalool thereby promoting formation of both cyclic motifs. The first oxidation process comprises the selective preparation of one of two possible epimeric epoxides via a tandem sequence of Lewis-acid catalysed epoxidation and resolution. The latter was achieved via a catalytic selenium-based redox system with either NFSI or molecular oxygen as the terminal oxidant. Interestingly, in this case, selenium proved to be a superior alternative to established palladium catalysts. The second synthesis project focused on the total synthesis of the two marine polyketides (+)-plakortolide E and (–)-plakortolide I. With considerations for maximising aspects of synthesis economy in mind, a synthetic approach based on the previously developed route for the construction of substituted γ-butyro lactones from (R)-linalool was designed. Preparation of a butenolide intermediate via elimination of the secondary hydroxyl group was followed by modifications of the prenyl side chain to afford an allylic acetate that served as a platform for the two key steps of the synthesis. These steps constitute an iron-catalysed allylic substitution to install the alkyl chain and a cobalt-induced endoperoxide formation. By using earth-abundant transition metals to enable chemoselective transformations and developing one-pot operations to couple functional group interconversions with constructive bond formations the step and pot economy of the synthesis could be enhanced. Thus, a protecting group free synthesis of both natural products was achieved in seven steps. The last part of this thesis deals with studies on the synthesis of the two novel meroterpenoids hypatulin A and hypatulin B that belong to the class of polycyclic polyprenylated acylphloroglucinols (PPAPs). The highly oxygenated bicyclic and tricyclic core of hypatulin A and hypatulin B, respectively, have a densely substituted cyclopentane core bearing three quarternary stereocenters. The synthetic approach described in this thesis focused on the five membered ring which was retrosynthetically traced back to 2-cyclopentenone as a suitable starting material. Installation of the substitutions and the generation of four stereocenters was realised by exploiting carbonyl chemistry. Since the construction of the last stereocenter proceeded exclusively with the undesired facial selectivity and delivered the epimeric product at C-3, the synthesis of both natural products could not be realised. Instead, the focus was redirected towards 3-epi-hypatulin B which was accessible via methoxycarbonylation through the addition of lithiated methoxyallene and an oxidative cleavage thereof with singlet oxygen. Translation of the photo-oxidation into a flow process resulted in an improved scalability and a faster reaction compared to a batch process. Cross metathesis with 2-methylpropene eventually afforded 3-epi-hypatulin B over 16 steps in total.
