| This thesis describes the total synthesis of the antitumor natural product cyclodepsipeptide (−)-doliculide and the first total synthesis of the cytotoxic natural product macrolide amphidinolide T1.; In the first part, the isolation, biological properties, and previous total synthesis of (−)-doliculide were reviewed, followed by total synthesis of (−)-doliculide. The key steps involved an iterative asymmetric sequence to construct the 1,3,5-syn,syn-trimethyl groups using Charette's asymmetric cyclopropanation and regioselective cyclopropane opening reactions, and an iterative sequence construct the 1,3-trans-diol unit using Sharpless asymmetric epoxidation and regioselective epoxide opening reactions.; In the second part, the isolation, biological properties, and biosynthesis of the natural product (+)-amphidinolide T1 are reviewed. Then our preliminary efforts to design and synthesize various fragments of (+)-amphidinolide T1 are presented, which led to successful completion of the first total synthesis of (+)-amphidinolide T1 (5.6% in overall yield in 16 steps, longest linear sequence from a Ghosh's syn-aldol reaction). The key development of synthetic methodologies includes: first, development of highly diastereoselective anti- and syn-aldol reactions from the same Ti enolate, second, the high yielding efficient cross metathesis of complex substrates, and the 5-membered ring oxocarbenium ion-mediated alkylation of a sulfone derivative and vinyl ether. |
