Total Synthesis of <i>des</i>-Thiomethyllooekeyolide A.

The first asymmetric total synthesis and validation of the structural assignment of <i>des</i>-thiomethyllooekeyolide A (<b>3</b>) is described, which features a Shiina macrolactonization and a late-stage pyran-hemiketal formation. The eight stereogenic centers of the C16-polyketide chain were installed by sequential aldol and crotylation reactions.