The Polyhydroxy Pyrrole (indole) The Inside Alkaloids Hyacinthacine, A, <sub> 1 </ Sub> And Swainsonine The Asymmetric Synthesis Of Research

Polyhydroxy pyrrole (or indole) alkaloids, possessing both unique structural unit and very important biological activities, have attracted great interest of synthetic chemists and medicinal chemists in the past decades. Thus it becomes a pursuing aim to explore versatile synthetic methodologies for those natural products, to which there remains need to develop novel reactions, new reagents and new methods by chemists, and which by medicinal chemists could study the structure-activity-relationship of those products and discover the potential therapeutic agents.Recently, our group has been contributed to developing novel asymmetric synthetic methodologies by using the abundant and cheap natural amino acids as the chiral sources, and has established one asymmetric synthetic method for the versatile chiral building block (R or S-13) with excellent stereoselectivity. The thesis of this work aims to explore a new process procedure for the synthesis of the building block from natural amino acids in a large scale, and then utilize the chiral building block in the total synthesis of the natural polyhydroxy pyrrole (or indole) alkaloids. This work includes the three main parts as follows:The first part of our work is to study the stereoselective allylation reaction of (3S,4S,5S)-13, and based on the successful results,we then have devoted ourselves to developing a new method for the diversity-oriented-synthesis of "Hyacinthacine A1-like" compounds, which might exhibit potentially interesting bioactivities. The achievements of this part are illustrated as follows:1.We initially survey the behavior of the chiral five-heterocyclic N,O-acetal block treated with trimethylsylallene in the presence of various Lewis acids, and found allylation on C-2 position of the building block could be achieved in the presence of BF3.Et2O,and afforded the desired product in an excellent stereoselectivity (dr>99%), of which the steric configuration was confirmed by the corresponding NOE analysis. 2.Based on the novel method, we worked on the total synthesis of 5-epi-Hyacinthacine A1,and finally obtained the impured target compound in the limited time.The second part of the work is, based on the same building block [(3S,4S,5S)-13], to study the asymmetric synthesis of polyhydroxy indolizidine Swainsonine. To accomplish the total synthesis of the natural product, we survey the key steps: allylation on the side chain of the intermediate 150 derived from the chiral (3S,4S,5S)-13;and selective reduction of the ketone 152.We found 152 could be obtained by the treatment of the Weinreb amide with allyl Grignard's reagent, and it could be highly selective reduced to the intermediate 153 by the reductive reagent bearing bulky groups. At last, we also studied in detail the synthesis of D-13 in large scales, and have explored the suitable procedure for preparing a large scale of the key block D-13, which helped the team to complete the asymmetric synthesis of the sex pheromone of hair crabs. Meanwhile, the work also paves a way to the asymmetric synthesis of the more complicated natural products such as lipid compounds cerebrosides.