The first total synthesis of concanamycin f (concanolide a) |
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Authors: | Toshima K Jyojima T Miyamoto N Katohno M Nakata M Matsumura S |
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Affiliation: | Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. toshima@applc.keio.ac.jp |
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Abstract: | A highly stereoselective total synthesis of the macrolide antibiotic concanamycin F (1), a specific and potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 18-membered tetraenic lactone and beta-hydroxyl hemiacetal side chain subunits. The C1-C19 18-membered lactone aldehyde 4 was synthesized through the intermolecular Stille coupling of the C5-C13 vinyl iodide 24 and the C14-C19 vinyl stannane 25, followed by construction of the C1-C4 diene and macrolactonization. Synthesis of 4 via a second convergent route including the esterification of the C1-C13 vinyl iodide 45 and the C14-C19 vinyl stannane 47 followed by the intramolecular Stille coupling was also realized. The highly stereoselective aldol coupling of 4 and the C20-C28 ethyl ketone 5 followed by desilylation provided 1 which was identical with natural concanamycin F. |
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