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Total Synthesis of (-)-Conolutinine
Xiangyang Feng1,2, Guangde Jiang2, Zilei Xia2
1Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University , 22 Xinong Road, Yangling 712100, Shaanxi, China.
Organic Letters
|August 29, 2015
Summary
The first enantioselective total synthesis of (-)-conolutinine was achieved in 10 steps. This study introduces key catalytic methods for constructing complex indole alkaloids and establishes the molecule's absolute configuration.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- (-)-Conolutinine is a complex pentacyclic indole alkaloid.
- Its total synthesis presents a significant challenge in organic chemistry.
- Previous synthetic routes have not achieved enantioselectivity.
Purpose of the Study:
- To develop the first enantioselective total synthesis of (-)-conolutinine.
- To establish a reliable synthetic route for accessing this complex natural product.
- To confirm the absolute configuration of (-)-conolutinine through asymmetric synthesis.
Main Methods:
- A 10-step synthetic sequence was designed and executed.
- Catalytic asymmetric bromocyclization of a tryptamine derivative was employed to construct the tricycle intermediate.
- Cobalt(II) acetylacetonate (Co(acac)2)-catalyzed alkene hydration was used for diastereoselective introduction of the tertiary alcohol.
Main Results:
- The first enantioselective total synthesis of (-)-conolutinine was successfully achieved in 10 steps.
- Key catalytic asymmetric reactions were utilized to control stereochemistry.
- The absolute configuration was determined to be (2S,5aS,8aS,13aR).
Conclusions:
- The developed synthetic strategy provides an efficient route to (-)-conolutinine.
- This work demonstrates the power of catalytic asymmetric methods in natural product synthesis.
- The established absolute configuration provides a definitive structural assignment for (-)-conolutinine.