- Diastereoselective Aldol Reactions of β-Silyloxy Ethyl Ketones. Application to the Total Synthesis of Bafilomycin A1
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Studies directed toward the C17-C18 aldol bond construction in the macrolide antibiotic bafilomycin A1 are described.The effect of the β-substituent in the aldol reactions of α-unsubstituted enolates is documented for various model compounds.The stereoselectivity of this process is critically dependent on the C21 and C23 oxygen protecting groups.Application of this methodology to the synthesis of bafilomycin A1 is reported.
- Evans, David A.,Calter, Michael A.
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- Total synthesis of bafilomycin A1
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A convergent synthesis of bafilomycin A1 (see structure) is presented, and relies on the Zn(OTf)2-mediated diastereoselective addition of alkynes to aldehydes. The coupling of a complex enyne with a sensitive aldehyde in the key step
- Kleinbeck, Florian,Carreira, Erick M.
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supporting information; experimental part
p. 578 - 581
(2009/04/14)
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- Total synthesis of (-)-bafilomycin A1
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A highly stereoselective total synthesis of (-)-bafilomycin A1, the naturally occurring enantiomer of this potent vacuolar ATPase inhibitor, is described. The synthesis features the highly stereoselective aldol reaction of methyl ketone 8b and
- Scheidt, Karl A.,Bannister, Thomas D.,Tasaka, Akihiro,Wendt, Michael D.,Savall, Brad M.,Fegley, Glenn J.,Roush, William R.
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p. 6981 - 6990
(2007/10/03)
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- Total synthesis of bafilomycin A1 relying on iterative 1,2-induction in acyclic precursors
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The macrolide bafilomycin A1 was synthesized starting from D-valine and D-mannitol as chiral progenitors of propionate units. Acyclic subunits corresponding to different parts of the molecule were constructed based on an iterative 1,2-asymmetric induction protocol as a distinctive feature of the synthesis. The assembly of two segments encompassing the entire carbon framework of the macrolide was achieved by using a Stille coupling. The resulting seco-ester was further manipulated to provide crystalline bafilomycin A1 via a conventional carbodiimide-mediated Keck-type macrolactonization.
- Hanessian,Ma,Wang
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p. 10200 - 10206
(2007/10/03)
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- Retro-aldol cleavage of bafilomycin derivatives
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The intermediates 3 and 4, useful in the preparation of new biologically active bafilomycin derivatives, were obtained via a thermal retro-aldol reaction in diphenyl ether. The starting materials 5 and 7 for the retro- aldol reaction were synthesized in a few steps from bafilomycin C1 (2) with or without a protective group at 7-OH.
- Granberg, Kenneth L.,Edvinsson, Karin M.,Nilsson, Kristina
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p. 755 - 758
(2007/10/03)
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- 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. 2. The assemblage and completion of the synthesis
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The total synthesis of the macrolide antibiotic, bafilomycin A1 (1), has been achieved by a convergent route involving aldol condensation between the 16-membered lactonic aldehyde 2 and the ethyl ketone 3, followed by desilylation.
- Toshima, Kazunobu,Yamaguchi, Hiroyuki,Jyojima, Takaaki,Noguchi, Yasunobu,Nakata, Masaya,Matsumura, Shuichi
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p. 1073 - 1076
(2007/10/03)
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