Total synthesis of bafilomycin A(1) relying on iterative 1,2-induction in acyclic precursors.
The macrolide bafilomycin A(1) 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 A(1) via a conventional carbodiimide-mediated Keck-type macrolactonization.
Hanessian
S
S
Department of Chemistry, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
Ma
J
J
Wang
W
W
Gai
Y
Y
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D018942:Macrolides; D008353:Mannitol / Q000737:chemistry; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D014633:Valine / Q000737:chemistry
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D018942:Macrolides; D008353:Mannitol; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases; D014633:Valine