Stereoselective Synthesis of the Cytotoxic 14-Membered Macrolide Aspergillide A

A stereoselective synthesis of the cytotoxic 14-membered macrolide aspergillide A has been performed. The preparation of a cis-2,6-disubstituted tetrahydropyran ring via stereoselective reduction of an intermediate cyclic hemiacetal was one key feature of the synthesis. The macrocyclic lactone ring was created by means of a ring-closing metathesis (RCM), whereby the new C=C bond displayed exclusively the undesired Z configuration. Conversion to the required E configuration was achieved via photochemical isomerization.