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Synthesis of (-)-sordarin
Shunsuke Chiba1, Mitsuru Kitamura, Koichi Narasaka
1Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Journal of the American Chemical Society
|May 25, 2006
Summary
The first total synthesis of (-)-sordarin was achieved using novel Ag(I)-catalyzed oxidative radical cyclization and Pd(0)-catalyzed intramolecular allylation. This research provides a new synthetic route for this complex molecule.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- (-)-Sordarin is a complex natural product with potential biological activities.
- Previous synthetic routes to sordarin and its analogs have been limited.
- A robust and efficient total synthesis is crucial for further biological evaluation and structural modification.
Purpose of the Study:
- To achieve the first total synthesis of (-)-sordarin.
- To develop novel synthetic methodologies applicable to complex natural product synthesis.
- To establish a reliable route for accessing sordarin and its derivatives.
Main Methods:
- Ag(I)-catalyzed oxidative radical cyclization of a cyclopropanol derivative to form a bicyclo[5.3.0]decan-3-one skeleton.
- Pd(0)-catalyzed intramolecular allylation to construct the bicyclo[2.2.1]heptan-2-one framework of sordaricin.
- Selective dihydroxylation of terminal alkenes using OsO(4) and PhB(OH)(2).
- Beta(1,2-cis)-selective glycosidation facilitated by a 1,3-anchimeric assistance from a 4-methoxybenzoyl group.
Main Results:
- Successful construction of the core bicyclic frameworks of (-)-sordarin and sordaricin.
- Efficient and selective introduction of key functional groups, including diols and the glycosidic linkage.
- Demonstration of the utility of the developed synthetic strategies in complex molecule synthesis.
Conclusions:
- The first total synthesis of (-)-sordarin has been accomplished.
- The developed synthetic route is efficient and utilizes key novel reactions.
- This work provides a valuable platform for the synthesis of sordarin analogs and related natural products.
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