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Total Synthesis of (-)-Flueggeacosine C
Lin Liu1, Trevor L Olson1, John L Wood1
1Department of Chemistry and Biochemistry, Baylor University, One Bear Place 97348, Waco, Texas 76798, United States.
Organic Letters
|August 23, 2024
Summary
This study presents the first total synthesis of the complex natural product (-)-flueggeacosine C. The efficient strategy utilizes key reactions like Liebeskind-Srogl coupling and an intramolecular Diels-Alder reaction.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Medicinal Chemistry
Background:
- Securinega alkaloids are a class of natural products with potential biological activities.
- (-)-Flueggeacosine C is a complex heterodimeric alkaloid presenting a significant synthetic challenge.
Purpose of the Study:
- To achieve the first total synthesis of (-)-flueggeacosine C.
- To develop an efficient and convergent synthetic strategy for complex alkaloid structures.
Main Methods:
- Convergent synthesis employing Liebeskind-Srogl cross-coupling.
- Acyloxy nitroso ring-expansion for benzoquinolizidine synthesis.
- Intramolecular Diels-Alder reaction for securinine skeleton construction.
- Copper-catalyzed hydroboration-oxidation for stereoselective alcohol introduction.
Main Results:
- Successfully synthesized the heterodimeric securinega alkaloid (-)-flueggeacosine C.
- Developed key intermediates, benzoquinolizidine 9 and securinine fragment 16.
- Demonstrated regio- and diastereoselective installation of a crucial secondary alcohol.
Conclusions:
- The developed synthetic route provides access to (-)-flueggeacosine C.
- The methodology showcases the utility of advanced organic reactions in complex molecule synthesis.
- This synthesis opens avenues for further biological evaluation and analog development.
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