Wolfgang Kramer, PhD

Photochemical Synthesis of Isoindolone Piperidines as GSK3/CDK Inhibitors

In this project we propose the photochemical synthesis of isoindolone piperidines and benzoazepines, both of which are important pharmaceutically active structures. The photochemical key step is the decarboxylative photocyclization, an established photochemical conversion for the synthesis of small to medium-sized ring systems. Substituents on the chromophore lead to the formation of regioisomers because of the asymmetric phenyl ring. The control of the cyclization reaction is one of the foci of this proposal. The direction of cyclization is either established before or after the electron transfer. Specific Aim 1 is dedicated toward investigating which pathway is taking place, and how the substituents influence that pathway. Once this has been established, photochemical syntheses will be developed which utilize the knowledge of the regiochemistry of cyclization. This will produce novel isoindolone piperidines and benzoazepines, and might also improve the synthesis of current compounds.