Computational and synthetic studies have elucidated the origins of stereodivergence in an oxy-Michael synthesis of 2,6-disubstituted tetrahydropyrans.

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.

Natural products • Multi-step synthesis • Thapsigargin • Titanium(II) complexes • Rhodium(I) complexes.