Total Synthesis of Branimycin: An Evolutionary Approach

Enev, Valentin S.; Felzmann, Wolfgang; Gromov, Alexey; Marchart, Stefan; Mulzer, Johann

Chem. Eur. J. 2012, 18(31), 9651-9668.

The first total synthesis of the macrolactone antibiotic branimycin (4) has been described. The key disconnection leads to a cis-dehydrodecalone core and a polyketide side chain which are connected via organometallic addition. The dehydrodecalone core was targeted via altogether five different approaches featuring various kinds of chiral elements and ring-closing methodology. In the end the most successful method starting from diepoxynaphthalene 109 was chosen to carry on with the synthesis. Thus the oxygen functions and carbon appendages were introduced via organometallic desymmetrization reactions to generate epoxy ketone 107, to which vinyl iodide 11 was added after conversion into the organolithium species. The synthesis was completed by introducing the ester side chain via Michael addition and subsequent macrolactonization.