Stereocontrolled Synthesis of (−)-Macrolactin A

The total synthesis of (−)-macrolactin A, a 24-membered macrolide, has been achieved using a newly developed 1,3-diol synthon for the introduction of two key stereogenic centers. The synthon was derived from sequential use of the Noyori asymmetric reduction followed by chiral sulfoxide methodology. Tellurium-derived cuprate organometallics offered an efficient and highly stereoselective means for installation of the C8 <i>Z/E</i>-diene, while the C15 <i>E/E</i>-segment was derived from a Julia−Lythgoe olefination. Yamaguchi lactonization was used to secure the macrocycle in a convergent approach with the longest linear sequence of 19 steps from Noyori alcohol <b>6</b>.