Asymmetric Synthesis of Arboduridine
Rui Yang1, Zeyu Zhou1, Huanfeng Jiang1
1Key Lab of Functional Molecular Engineering of Guangdong Province, School of Chemistry & Chemical Engineering, South China University of Technology, Wushan Road-381, Guangzhou, 510641, P. R. China.
Angewandte Chemie (International Ed. in English)
|December 1, 2023
Summary
The first asymmetric total synthesis of arboduridine, a monoterpenoid indole alkaloid, is reported. Key steps included enantioselective Michael reactions and cascade cyclizations to construct its complex ring system.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Medicinal Chemistry
Background:
- Monoterpenoid indole alkaloids represent a significant class of natural products with diverse biological activities.
- Arboduridine is a complex alkaloid whose total synthesis presents a considerable synthetic challenge.
Purpose of the Study:
- To achieve the first asymmetric total synthesis of arboduridine.
- To develop a novel synthetic strategy for constructing the intricate A/B/D tricyclic core and other key structural features.
Main Methods:
- Enantioselective Michael reaction for A/B/D ring system construction.
- Intramolecular nucleophilic addition and α-amination for piperidine ring formation.
- Horner-Wadsworth-Emmons reaction and reduction cyclization cascade for pyrrolidine and tetrahydrofuran ring synthesis.
Main Results:
- Successful construction of the tricyclic A/B/D ring system with defined stereochemistry.
- Efficient formation of the piperidine, pyrrolidine, and tetrahydrofuran rings.
- Completion of the first asymmetric total synthesis of arboduridine.
Conclusions:
- The developed synthetic route provides a viable pathway to arboduridine and related analogs.
- This synthesis showcases the utility of key reactions in constructing complex alkaloid frameworks.
- The methodology can be applied to the synthesis of other challenging natural products.
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