Total synthesis of a novel macrotetrolide

The total synthesis of a novel macrotetrolide, an isobutyl nonactin analog, has been achieved in 15% yield by coupling both enantiomers of the corresponding nonactic acid analogs followed by macrolactonization. These building blocks were prepared starting from β-ketoester in nine steps and 34% overall yield, in an efficient and highly stereoselective sequence. The key steps of the strategy are asymmetric hydrogenation, chelation-controlled allylation, intramolecular haloetherification of bishomoallylic ether presenting a trisubstituted double bond deactivated by an ester, and finally a stereoselective reduction of α-bromoester.