I. The total synthesis of leucascandrolide A. II. Studies directed toward the total synthesis of ingenol.

摘要

The first part of this dissertation describes the total synthesis of the marine natural product (+)-leucascandrolide A completed in conjunction with Mr. Christopher Hamblett in the laboratories of Professor James Leighton. The isolation, structure determination, biological activity of leucascandrolide A are discussed. Efforts from other laboratories toward the total synthesis of leucascandrolide A are briefly reviewed. Our approaches are then discussed, beginning with an unsuccessful route using a silylformylation reaction developed in our laboratory and concluding with our successful oxymercuration-formylation strategy. Highlights of the sequence are an oxymercuration-formylation reaction, a novel hydroformylation-Sakurai allylation sequence for the construction of a trans-fused tetrahydropyran, and an extension of an alkoxycarbonylation reaction for preparing cis-fused tetrahydropyran rings to complicated triol substrates. During the synthesis, in conjunction with Dr. Spencer Dreher, a key advance in our oxymercuration chemistry was made, allowing the production of more useful protecting groups.; The second part of the dissertation describes efforts toward a total synthesis of the tumor promoter ingenol in conjunction with Mr. Sergei Bolshakov. The isolation, structure determination, and biological activity of this unusual natural product are first discussed, followed by review of other relevant synthetic approaches that address the key in-out bridgehead stereochemistry problem. Our efforts to synthesize ingenol via intramolecular furan, oxazole, or cyclopentadiene Diels-Alder reactions are then discussed. While the key synthetic reaction in this proposed route has not been validated, useful information concerning aldol and Diels-Alder reactions of sterically hindered systems was discovered en route.