Efficient Total Synthesis of Khafrefungin: Convergent Approach Using Suzuki Coupling under Thallium-free Conditions Toward Multigram-scale Synthesis

An efficient and practical synthetic route to khafrefungin, an antifungal agent, has been developed based on successive coupling of three components, 3, 4, and then 2. A key step of the synthesis is the Suzuki coupling of 2 and 10, in which the use of toxic thallium ethoxide has been avoided, and the coupling adduct (11) was obtained in multigram-scale quantities.