Synthetic studies on bafilomycin A1:: stereoselective synthesis of the enantiopure C1-C11 fragment

The synthesis of the enantiopure C-1-C-11 fragment of bafilomycin A(1) has been achieved with a 4% overall yield over 18 steps from (R)-(+)-citronellol. Key steps involve Sharpless asymmetric epoxidation, Miyashita reaction of a gamma,delta-epoxymethacrylate with trimethylaluminum in the presence of water, bis-OTMS selective Swern oxidations, Corey-Fuchs alkyne formation, Negishi's carbometalation, and stereoselective formation of the C-2-C-3 trisubstituted bond of the conjugated diene by a Wittig-type olefination of the alpha, beta-unsaturated C-3-C-11 aldehyde with the ylide derived from the readily available phosphonium salt [Cl-, Ph3P+CH(OMe)COOMe]. (C) 2004 Elsevier Ltd. All rights reserved.