Supervisors: vanemteadur Lauri Vares (Tartu Ülikool), professor Peter Somfai (Tartu Ülikool, Lundi Ülikool)
Opponent: Prof. Nina Kann
Chalmers University of Technology
Department of Chemical and Biological Engineering
Acetogenins are an interesting group of natural compounds, which can exhibit selective cytotoxicity towards tumorous cell-tissue. Although acetogenins have been studied for a while now, the relationship between their structure and bioactivity has not been fully elucidated. In this work six analogues of acetogenins were synthesized and their bioactivity was assessed in a model tumorous cell line. The developed synthetic route can be adjusted for all of the analogues synthesized - this approach allows units of the compound to be prepared separately, and joined together in later stages to form the end-compound. The spatial arrangement of the atoms in the structure, called stereochemistry, was also under scrutiny during the synthesis. The three-dimensional positioning within the structure can often be very important for the bioactivity. Four of the synthesized analogues, similar in type, retained bioactivity in model tumour cells causing cell death, although being less active than their natural counterparts. Two other synthesized analogues exhibited negligible bioactivity in the tested cell-line. The second part of the presented work discusses the synthesis of amino acid like derivates. These relatively small, yet important molecules can be used as 'building blocks' in the synthesis of more complex molecules. The study entailed the synthesis of these derivates via asymmetric transfer of a hydrogen atom coupled with dynamic kinetic resolution, giving high yields. During the reaction one hydrogen atom was added to the starting material with high stereoselectivity, noting that the hydrogen atom originated from another organic compound in the reaction mixture and not from hydrogen gas. The developed method permits the reaction to be run at room temperature and in air atmosphere, omitting the use of high pressures and hydrogen gas, often used for similar transformations.