Total Syntheses Of (±)-Fawcettimine,(±)-lycoflexine,(±)-Lycoflexine N-oxide,and (+)-Aspicilin

This dissertation focuses mainly on total syntheses of lycopodium alkaloids (±)-fawcettimine,(±)-lycoflexie,(±)-lycoflexine N-oxide, and macrolide natural product (+)-aspicilin. It consisted of the following four parts:Chapter1. Review on the Total Synthesis of FawcettimineLycopodium alkaloids are quinolizine-, pyridine-, or pyridone-type alkaloids. Some Lycopodium alkaloids are potent inhibitors of acetylcholinesterase (AChE). Fawcettimine, an important biogenetic precursor of other Lycopodium alkaloids, has become an attractive target for the synthetic community. The isolation, structure and total syntheses of fawcettimine were introduced briefly.Chapter2. Studies on the Total Syntheses of (±)-Fawcettimine,(±)-Lycoflexine, and (±)-Lycoflexine N-Oxide.Four synthetic routs have been investigated. In the end, we have developed an efficient and unified strategy for the total syntheses of (±)-fawcettimine,(±)-lycoflexine, and (±)-lycoflexine N-oxide from commercially available5-methylcyclohex-2-enones in14,14and15steps, respectively. The key features include a Sakurai reaction, one-pot annulation to construct fused6/5bicyclic enedione, a microwave-promoted Diels-Alder reaction, and double SN2reactions. Notably, we have completed the first total synthesis of (±)-lycoflexine N-oxide.Chapter3. Review on the Total Synthesis of (+)-AspicilinThe polyhydroxylated macrocyclic lactone (+)-aspicilin was first isolated in 1900by Hesse from Lecanora-ceae family of lichen. It showed promising inhibitory activity on the proliferation of A549(IC50=14.7μm over24h), HeLa (IC50=17.9μmover24h), and MCF7(IC50=12.0μmover24h) cancer cell lines. The literature on the total synthesis of (+)-aspicilin and the synthesis of macrolide natural products in our group are reviewed briefly.Chapter4. Studies on the Asymmetric Synthesis of (+)-Aspicilin.Based on the convergent synthetic strategy, a concise and efficient asymmetric synthesis of the18-membered precursor of (+)-aspicilin has been achieved within9steps staring from cheap and commercial available a-D-mannose and (S)-proplene oxide. This synthesis involved Kumada coupling, zinc-mediated fragmentation, Horner-Wadsworth-Emmons olefination, and ring-closing etathesis as the key steps.