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A facile asymmetric route to (-)-aphanorphine
Hongbin Zhai1, Shengjun Luo, Chengfeng Ye
1Laboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China. zhaih@mail.sioc.ac.cn
The Journal of Organic Chemistry
|October 11, 2003
Summary
Researchers efficiently synthesized 8O-methylaphanorphine, a key intermediate for the marine alkaloid (-)-aphanorphine. This enantioselective synthesis involved a novel Friedel-Crafts alkylative cyclization to construct the benzazepine core.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Marine alkaloids, such as aphanorphine, exhibit complex structures with potential pharmacological activities.
- Efficient synthetic routes are crucial for accessing and studying these valuable natural products.
Purpose of the Study:
- To develop an efficient and enantioselective formal synthesis of the 3-benzazepine marine alkaloid (-)-aphanorphine.
- To establish a reliable method for constructing the core benzazepine scaffold with stereochemical control.
Main Methods:
- The synthesis commenced with 4-methoxyphenylacetaldehyde.
- Key steps included a Friedel-Crafts alkylative cyclization for ring B formation.
- Stereospecific introduction of a benzylic quaternary carbon center was achieved.
Main Results:
- 8O-methylaphanorphine was synthesized in an overall yield of 36% over nine steps.
- The synthesis demonstrated an efficient enantioselective approach.
- The Friedel-Crafts cyclization successfully formed the benzazepine ring system.
Conclusions:
- This work presents an efficient enantioselective formal synthesis of (-)-aphanorphine.
- The developed methodology provides a viable route to complex benzazepine alkaloids.
- The stereospecific introduction of the quaternary center is a significant achievement in the synthesis.