Related Experiment Videos
Total Synthesis of Bafilomycin A(1)
Kazunobu Toshima1, Takaaki Jyojima, Hiroyuki Yamaguchi
1Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223, Japan.
The Journal of Organic Chemistry
|May 16, 1997
Summary
The total synthesis of bafilomycin A(1), a potent vacuolar H(+)-ATPase inhibitor, was achieved. This macrolide antibiotic synthesis utilized a convergent route with key chiral building blocks.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Biochemistry
Background:
- Bafilomycin A(1) is a potent inhibitor of vacuolar H(+)-ATPase, crucial for cellular processes.
- The complex structure of bafilomycin A(1) presents a significant challenge for total synthesis.
Purpose of the Study:
- To achieve the highly stereoselective total synthesis of bafilomycin A(1).
- To develop a convergent synthetic route for this macrolide antibiotic.
Main Methods:
- Convergent synthesis involving a 16-membered tetraenic lactone and a beta-hydroxyl hemiacetal side-chain.
- Coupling of vinyl iodide and vinylstannane fragments for lactone construction.
- Aldol coupling and desilylation to yield the final product.
Main Results:
- Successful synthesis of bafilomycin A(1) identical to the natural product.
- Key synthetic intermediates were efficiently prepared from readily available chiral starting materials (D-glucose, ethyl (S)-lactate, methyl (S)-3-hydroxy-2-methylpropionate).
Conclusions:
- A highly stereoselective total synthesis of bafilomycin A(1) has been accomplished.
- The developed convergent strategy is effective for constructing complex macrolide antibiotics.