Total synthesis of bafilomycin V(1): a methanolysis product of the macrolide bafilomycin C(2).
A synthesis of bafilomycin V(1), a methanolysis product of the macrolide natural product bafilomycin C(2), is described. The route utilizes chiral nonracemic allenylzinc reagents, prepared in situ from propargylic mesylates, to access key segments of this methyl ester. The acetylenic moieties of the derived homopropargylic alcohol adducts play an important role in further elaboration of these subunits. Final assemblage of the 25-carbon chain, containing 12 stereocenters, an alpha-methoxy Z,E 1,3-dienic ester, and an additional E,E 1,3-diene, was achieved through Stille coupling of an acetylene-derived vinyl stannane and vinyl iodide of approximate equal complexity. Attempted cyclization of several C15 hydroxy acid derivatives to the 16-membered lactone bafilomycin A(1), a potent inhibitor of vacuolar ATPases, could not be achieved.
Marshall
James A
JA
Department of Chemistry, University of Virginia, McCormick Road, P.O. Box 400319, Charlottesville, Virginia 22904, USA. jam5x@virginia.edu
Adams
Nicholas D
ND
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000737:chemistry*; D008958:Models, Molecular
D000900:Anti-Bacterial Agents; D018942:Macrolides; C449923:bafilomycin C2; C449924:bafilomycin V1; D008697:Methane