Enantioselective Synthesis of the Morphine Skeleton by a Photocyclisation approach

• Applicant: Dr. Niels Münster
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 314394209

The research project focuses on the efficient construction of the morphine skeleton that can be found in many potent drug substances. Previous synthetic approaches have the disadvantages of needing many steps and/or being unsuitable for a preparation on larger scale. The planned synthetic route includes the development of an enantioselective catalysed photocyclisation to build up the quaternary stereocenter of the morphine core and close the dihydrobenzofuran ring simultaneously. In contrast to the enantioselective catalysis of photochemical cycloaddition reactions, where there has seen major progress in recent years, only a few methods are known to control absolute stereochemistry of photo-induced electrocyclisations. Synthetic solutions for this would increase the application potential of this atom economic and efficient C-C-binding reaction enormously. In a further following key step the tetracyclic basic structure of the target skeleton will be constructed via an enyne metathesis cascade. The application of both reactions would enable a fast access to the morphine skeleton whereby pharmacological interesting morphine derivatives would be more readily accessible than before. To demonstrate the applicability of the key reactions, after successful development, they will be used for the synthesis of the important opioid (-)- morphine finally.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Martin D. Smith, Ph.D.