Diastereoselective synthesis of an advanced intermediate of thapsigargin and other 6,12-guaianolides using a RCEYM strategy

A new and flexible approach toward the synthesis of 6,12-guaianolide anticancer drugs such as trilobolides or thapsigargin has been developed that could be applied to the preparation of analogues with a modified ring system. The synthesis starts from commercial 2-methylcyclopentane-1,3-dione, only relying on diastereoselective reactions for the construction of the stereogenic centers at C1, C3, C6, and C10 and features a high-yielding ring-closing enyne metathesis (RCEYM) step for the formation of the [5,7] bicyclic core