Synthese und Funktionalisierung von bioaktiven 7-Azaindolderivaten sowie Strukturvariationen von Sulfoximinen
- Synthesis and functionalization of bioactive 7-azaindole derivatives as well as structural variations of sulfoximines
Wiezorek, Stefan; Bolm, Carsten (Thesis advisor); Albrecht, Markus (Thesis advisor)
Dissertation / PhD Thesis
Dissertation, RWTH Aachen University, 2020
Three projects were part of this work. In the first project which was developed in a collaboration with Prof. Dr. Martin Zenke, UK Aachen, multiple azaindole as well as Pacific-Blue derivatives were synthesized. Using different synthetic approaches, four literature-known compounds, ten new azaindole derivates as well as five novel Pacific-Blue-azaindole derivates were prepared. These compounds were screened at different concentration by Prof. Zenke and co-workers on their activity towards the mast cell lines HMC 1.1 and HMC 1.2 to identify their potential as tyrosine kinase inhibitors against the mutation D816V. Additionally, selected azaindole derivates were tested by Prof. Dr. Georg Karpel-Massler, UK Ulm, to determine their anti-neoplastic activity towards glioblastoma cells. Among these derivates three molecules showed promising inhibitory effects on the cell line U87MG. Therefore, the molecular characterization of the mechanisms which form the basis of the biological activity as well as the expansion to different cell lines are subject of current investigations. In the second project the goal was to synthesize a sulfoximine building-block as S methyl-S-imidazolesulfoximine. After optimization of the protecting groups for the imidazole nitrogen, the corresponding NNs-sulfoximine could be obtained in an overall yield of 39% starting from S-methyl-S-sulfide. The third project was developed during the optimization of the imination reaction. A one-pot procedure was developed from existing imination and oxidation methods leading directly to NNs-sulfoximines starting from the corresponding sulfides. The method was optimized leading to yields up to 73%.