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Preparation of a Corannulene-functionalized Hexahelicene by CopperI-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units
Published on: September 18, 2016
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Total Synthesis of (-)-Neocucurbol C Enabled by Pattern Recognition and MHAT Cyclization
Li-Ping Zhong1, Cyrus Gudeman1, Jingsong Zhen1
1Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
Journal of the American Chemical Society
|August 4, 2025
Summary
This study presents the first total synthesis of (-)-neocucurbol C, a complex diterpene. The research also identified novel compounds with potential anticancer activity from synthetic intermediates.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Medicinal Chemistry
Background:
- (-)-neocucurbol C is a diterpene natural product with a complex polycyclic structure and nine stereocenters.
- Existing synthetic routes to such complex molecules are limited, hindering further research and development.
Purpose of the Study:
- To achieve the first asymmetric total synthesis of (-)-neocucurbol C.
- To evaluate the cytotoxic activity of (-)-neocucurbol C and its synthetic intermediates against cancer cell lines.
Main Methods:
- Utilized (+)-nootkatone from the chiral pool as a starting material.
- Employed hydrodealkenylative bond fragmentation, Suzuki-Miyaura cross-coupling, oxidative dearomatization cyclization, and metal-catalyzed hydrogen atom transfer (MHAT)-initiated reductive radical cyclization.
- Completed the synthesis in 24 steps.
Main Results:
- Successfully synthesized (-)-neocucurbol C, establishing its complex 6/6/5/5/6 polycyclic skeleton and nine stereocenters.
- Identified several synthetic intermediates exhibiting promising cytotoxicity against various cancer cell lines.
Conclusions:
- The developed synthetic strategy provides a viable route to (-)-neocucurbol C and related complex diterpenes.
- The identified lead compounds offer potential for further development as anticancer therapeutics.
![Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60786.jpg&w=3840&q=50)
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