The First Synthesis Of (+)-Serinolamide A & Studies On Asymmetric Synthesis Of Amaryllidaceae Alkaloids: Crinane, Augustamine And Noraugustamine

Based on the asymmetric total synthesis of natural products research, this thesis mainly focused on the total synthesis study of marine natural product Serinolamide A and Amaryllidaceae alkaloids:Crinane, Augustamine and Noraugustamine. It could be divided into three parts:Chapter 1. The first synthesis of Serinolamide A by a chiral pool methodSerinolamide A is the extract of Lyngbya majuscule. This chapter briefly described its biological activity, as well as the synthesis of related compounds. Based on the previous studies, we started the total synthesis of Serinolamide A. It has been synthesized for the first time in 9 steps from readily available material L-serine with 30% overall yield, which provides the facility for further tests of biological activity due to the synthetic efficiency and simplicity. In addition, the direct synthesis strategy is high efficient and has the prospect to prepare other similar endocanabinoid lipids.Chapter 2. The review on asymmetric synthesis of 3a-aryl hydroindole type Amaryllidaceae alkaloidsAmaryllidaceae alkaloids can be divided into eighteen kinds by its basic framework. As one of the important branches,3a-aryl hydroindole type alkaloids have attracted wide attention of chemical workers about the synthesis due to their wide range of biological activities and unique structures. A large number of efficient synthetic methods have been developed. The critical and challenging element in the total synthesis of these alkaloids is the construction of chiral congested quaternary center located at the hydroindolone bridge head (C3a). This chapter mainly summarized the predecessors’ works about the asymmetric synthesis of such alkaloids. On the basis of previous studies, we put forward our ideas for the synthesis of these molecules.Chapter 3. The studies on asymmetric synthesis of Amaryllidaceae alkaloids:Crinane, Augustamine and NoraugustamineWe chose Crinane as our initial target for 3a-aryl hydroindole type alkaloids synthesis. In the synthesis design of Crinane, we initially tried to use organocatalysts to construct the chiral quaternary carbon center, which failed finally. After carefully investigating, we successfully completed the construction of the chiral quaternary carbon with 93.8% ee value by Pd-catalyzed allyl-allyl coupling reaction. The total synthesis of Crinane have been completed in 12 steps including the key steps such as Michael addition, RCM reaction et al.. Up to the completing synthesis of Crinane, we studied the asymmetric total synthesis of natural products Augustamine and Noraugustamine. Now the key intermediates have been obtained and they are still in the further study.