| This thesis describes the first total synthesis and structural revision of the cytotoxic natural product amphidinolide W and progress toward the synthesis of the antitumor natural product lasonolide A.; In the first part, the isolation and biological properties of amphidinolide W were introduced followed by a review of the synthetic strategies of other amphidinolide compounds. The design of a retrosynthetic route for amphidinolide W, which sets four stereogenic centers by asymmetric synthesis, is followed by a detailed discussion of its total synthesis which has been carried out in a convergent manner via cross metathesis---Yamaguchi macrolactonization sequence. The synthesis features Sharpless asymmetric dihydroxylation, diastereoselective alkylation, efficient cross metathesis of functionalized substrates, and novel functional group transformations using selective lipase-catalyzed hydrolysis of the primary acetate group. Of particular note, the C6 absolute stereochemistry of amphidinolide W has now been revised through our synthesis.; In the second part, the isolation and biological properties of lasonolide A were introduced. The previous synthetic approaches toward lasonolide A including two total syntheses were described, especially the construction of two tetrahydropyran fragments. Our studies toward the total synthesis of lasonolide A, which focus on the synthesis of two tetrahydropyran moieties, were discussed in detail. The top tetrahydropyran ring was constructed by an intramolecular 1,3-dipolar cycloaddition via bicyclic isoxazoline which stereoselectively built the quaternary stereocenter present in the molecule. The bottom tetrahydropyran ring was assembled by a catalytic asymmetric hetero-Diels-Alder reaction. Three stereocenters were enantioselectively installed in this single step reaction. |
