Description
Many of the drugs currently used in medicine practice are mixtures of enantiomers. For some drugs, single-enantiomer formulations can provide greater selectivities for their biological targets, and improved efficiency than a mixture of enantiomers. Therefore the development of new synthetic strategies of enantiomericaly pure therapeutics is major aim of many research groups. Therefore the project intends to focus on the development of new enantioselective synthetic methods that allow for the preparation of commercially available drug. The main scientific objective of this proposal is to explore the possibility of stereoselective synthesis of painkiller drug using tetrasubstituted α,β-unsaturated compound as a key precursor. We intend to focus our research on the development of synthetic methods that allow for the preparation of tetra-substituted alkenes that could be directly changed to the commercially available drug. The results of the project will be published in international journals and will be presented at International conferences. The results of this project will mostly benefit international group of scientists.
Summary of project results
The project concerned important synthetic problem, namely the synthesis of tetrasubstituted alkenes. We envisioned to developed highly regioselective and efficient methods suitable for synthesis of tetrasubstituted alkene derivatives that could be applied for synthesis of know painkiller Tapentadol. Our work demonstrate that synthesis of tetrasubstituted alkenes remains a difficult synthetic issue. However, we were able to synthesize the tetrasubstituted cinnamic acid derivative with good yield and regioselectivity. Moreover we simplify the final purification procedure, so it will facilitate large-scale synthetic procedures. We also proved that Ni(dme)Cl2 can be an effective catalyst in carbometallation reaction, which due to its air stability may be an interesting complement to the catalyst already known and used in this process. Additionally, we proved that commercially available catalysts could be efficiently used for asymmetric hydrogenation of tetrasubstituted alkenes, however we are still exploring this subject to find more stereoselective catalysts. Furthermore, the results of this project were presented on scientific conferences and described in several bachelor or master theses as well as included to scientific achievements of Principal Investigator needed for habilitation degree. Recently, part of results were published in reputable international journal.
Summary of bilateral results