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14:18
A Strategy for Sensitive, Large Scale Quantitative Metabolomics
Published on: May 27, 2014
Total synthesis of (-)-gambierol
Haruhiko Fuwa1, Noriko Kainuma, Kazuo Tachibana
1Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Journal of the American Chemical Society
|December 12, 2002
Summary
Researchers achieved the first total synthesis of (-)-gambierol, a marine toxin. This involved a convergent strategy using Suzuki-Miyaura coupling for the core and Stille coupling for the side chain.
Area of Science:
- Organic Chemistry
- Marine Natural Products Chemistry
Background:
- Marine polycyclic ether toxins pose significant synthetic challenges.
- (-)-Gambierol is a complex marine toxin with potential biological activity.
Purpose of the Study:
- To achieve the first total synthesis of (-)-gambierol.
- To develop novel synthetic strategies for complex polycyclic ethers.
Main Methods:
- Convergent synthesis utilizing Suzuki-Miyaura cross-coupling for fragment union.
- Late-stage introduction of a sensitive triene side chain via Stille coupling.
- Stereoselective construction of ring fragments using SmI(2)-induced reductive cyclization and hetero-Michael reactions.
Main Results:
- Successful construction of the octacyclic polyether core of (-)-gambierol.
- Efficient synthesis of key ABC and EFGH ring fragments.
- Completion of the total synthesis of (-)-gambierol through strategic coupling reactions.
Conclusions:
- The developed synthetic route provides a viable pathway to (-)-gambierol.
- The study highlights the utility of modern cross-coupling reactions in complex molecule synthesis.
- This synthesis opens avenues for further investigation into the biological properties of (-)-gambierol.
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