Total synthesis of bafilomycin A1
Florian Kleinbeck1, Gabriela J Fettes, Lee D Fader
1ETH Zürich HCI H335, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|February 21, 2012
Summary
This study presents a novel convergent synthesis for bafilomycin A(1), a powerful V-type ATPase inhibitor. The innovative approach utilizes key fragment coupling and ruthenium-catalyzed reactions for efficient construction of the molecule.
Area of Science:
- Organic Synthesis
- Medicinal Chemistry
- Biochemistry
Background:
- Bafilomycin A(1) is a potent inhibitor of V-type ATPases, crucial cellular pumps.
- Developing efficient synthetic routes for complex natural products like bafilomycin A(1) is essential for further research and therapeutic development.
Purpose of the Study:
- To present a novel convergent synthesis of bafilomycin A(1).
- To establish an alternative strategy to traditional cross-coupling methods for constructing the molecule's core structure.
Main Methods:
- Utilized zinc triflate-mediated diastereoselective addition for key fragment coupling.
- Employed ruthenium-catalyzed trans-reduction to install the C10-C13 trans,trans-diene subunit.
- Applied selective oxidation of a secondary hydroxyl group in a triol intermediate.
Main Results:
- Successfully achieved a convergent synthesis of bafilomycin A(1).
- Demonstrated an efficient alternative to palladium-catalyzed cross-coupling strategies.
- Established a robust method for installing the critical trans,trans-diene moiety.
Conclusions:
- The presented synthesis offers an efficient and alternative route to bafilomycin A(1).
- The synthetic strategy highlights novel applications of ruthenium catalysis in complex molecule construction.
- This work facilitates further investigation into the biological roles and therapeutic potential of V-type ATPase inhibitors.
