- Total synthesis of bafilomycin A1
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The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A1 (1), the first specific potent inhibitor of vacuolar H+-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and β-hydroxyl hemiacetal side-chain subunits. The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization. The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A1. The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.
- Toshima,Jyojima,Yamaguchi,Noguchi,Yoshida,Murase,Nakata,Matsumura
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p. 3271 - 3284
(2007/10/03)
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- Total synthesis of bafilomycin A1. 1. Syntheses of the C5~C11, C12~C17 and C18~C25 segments
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The effective syntheses of the C5~C11 (2), C12~C17 (3) and C18~C25 (4) segments, which are promising synthetic intermediates toward the total synthesis of the macrolide antibiotic, bafilomycin A1 (1), were described.
- Toshima,Jyojima,Yamaguchi,Murase,Yoshida,Matsumura,Nakata
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p. 1069 - 1072
(2007/10/03)
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