The first total synthesis of concanamycin f (concanolide a).
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.
Toshima
K
K
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
Jyojima
T
T
Miyamoto
N
N
Katohno
M
M
Nakata
M
M
Matsumura
S
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000900:Anti-Bacterial Agents; D018942:Macrolides; C076477:concanamycin F