Development of a synthetic methodology for thienopyridinone and thienodiazepinone derivatives and benzimidazo-oxazepines

Korkmaz Çokol, Nalan
Thienopyridinone and thienodiazepinone derivatives are known for their diverse pharmacological activities. Pyridinones and diazepinones play an important role in inhibition of some enzymes such as glycogen synthase kinase-3β and regulation of various cell functions. They also demonstrate an interesting property in the repair of damaged DNA. In the first part of this thesis, we synthesized thienopyridinone and thienodiazepinone derivatives. Aminothiophene derivatives were successfully synthesized via Gewald type reaction which was followed by the conversion to iodo- and bromo-thiophene derivatives via modified Sandmayer reaction. Sonogashira cross-coupling reaction was used to generate carbon-carbon single bond between the thiophene ring and alkyne derivatives. Cyclization of those compounds with hydrazine hydrate gave target molecules. Imidazole derivatives exhibit a wide range of bioactivities, therefore they are of intensive synthetic interest. They are also used as precursors for the synthesis of heterocycles having pharmaceutical properties. In the second part of this thesis, a concise and efficient approach to the synthesis of benzimidazo-oxazepine derivatives was developed. The synthetic strategy relies on the O-propargylation of salicyl aldehyde derivatives followed by Sonogashira cross-coupling reaction for further derivatization. Resulting alkyne derivatives were converted into the corresponding imidazole rings under acidic condition. NaH-mediated cyclization gave desired compounds, benzimidazo-oxazepines.
Citation Formats
N. Korkmaz Çokol, “Development of a synthetic methodology for thienopyridinone and thienodiazepinone derivatives and benzimidazo-oxazepines,” Ph.D. - Doctoral Program, Middle East Technical University, 2018.