| This thesis describes our studies on the synthesis of spiroketals by intramolecular spirocyclization of glycal epoxide substrates.;First, a 68-membered library of stereochemically complex benzannulated spiroketals was synthesized for discovery screening. The library was prepared by stereoselective epoxidation of glycals followed by kinetically-controlled spirocyclization of benzannulated sidechain alcohols. The activity of individual library members in various assays suggests that stereochemistry, spiroketal ring size, and position of the aromatic ring are critical factors for binding to targets.;Next, using a panel of electronically diverse benzannulated substrates, we studied the mechanism of a MeOH-catalyzed epoxide-opening spirocyclization with inversion of configuration. Our results indicate that MeOH is second-order catalyst in the desired spirocyclization, while acetone from the DMDO reagent is a first-order inhibitor.;Finally, we have developed an efficient synthetic approach toward the renal-protective spiroketal natural products acortatarins A and B. The key step is a reductive spirocyclization reaction of a glycal epoxide and a pendant aldehyde nucleophile. |
