Organo-catalytic asymmetric synthesis of cannabinoids

• Applicant: Professor Dr. Stefan Bräse
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 40280143

Cannabinoids belong to an important class of biologically active molecules modulating various receptors. Among them, the CB1 and the CB2 receptor which are both membrane bound GPCR (G-protein coupled receptors). Therefore, cannabinoid receptors are important new drug targets. Besides their use as anti-obesity drugs, CBi antagonists have potential for the treatment of neurodegenerative diseases including Parkinson's and Huntington's disease, and for the therapy of drug dependence. in this proposal we will focus on two strategies for the generation of CB1 and CB2 modulating molecules prepared by organo-catalysis. The second strategy uses our target-oriented synthesis of natural occurring cannabinoids and their congeners. In the first step, chromenes are formed using an organo-catalytic oxa-Michael reaction. Subsequent functionalization including the organo-catalyzed Diels-Alder reaction will lead to a de-novo synthesis of cannabinoids. An application will focus on two so-far no synthesized natural products having the Benzopyran skeleton. The second approach based on the recently discovered carbene-mediated synthesis of coumarins. The latter proofed to be active cannabinoids in vivo and in vitro. We will continue along these lines and expand this to an asymmetric version.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1179: Organocatalysis