The first total synthesis of concanamycin F (concanolide A)

A highly stereoselective total synthesis of the macrolide antibiotic concan amycin F (1), a specific and potent inhibitor of vacuolar H+-ATPase, has be en achieved by a convergent route involving the synthesis and coupling of i ts 18-membered tetraenic lactone and beta -hydroxyl hemiacetal side chain s ubunits. The C1-C19 18-membered lactone aldehyde 4 was synthesized through the intermolecular Stills coupling of the C5-C13 vinyl iodide 24 and the C1 4-C19 vinyl stannane 25, followed by construction of the C1-C4 diene and ma crolactonization. Synthesis of 4 via a second convergent route including th e esterification of the C1-C13 vinyl iodide 45 and the C14-C19 vinyl stanna ne 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 concan amycin F.