Total Synthesis of Bafilomycin A1 Relying on Iterative 1,2-Induction in Acyclic Precursors

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.