Indole The West Pyridine Alkaloid Swainsonine And Cyclic Peptide The Lactone Thalassospiramides Class Molecular Synthetic Study Of The Rigid Ring

The synthesis of natural products is the cross-field concerning both natural product chemistry and organic synthetic chemistry. It becomes the driving force in the development of synthetic methodology and strategies, and also provides an important way for the discovery of new reactions, new reagents, new methods and new theories. Structural modification, molecular reconstruction, and structure-activity relationship research on natural products can serve as not only a direct way for utilizing natural products reasonablely, safely and effectively, but also as an important source of new drug discovery.Multi-hydroxy alkaloids containing pyrrolizidine or indolizidine skeleton are an important class of heterocyclic alkaloids widely occurring in nature. Since the vast majority of such alkaloids have a wide spectrum of biological activities and unique chemical structure, they attract a large number of organic synthetic and medical chemists in recent years. For example, Swainsonine containing indolizidine skeleton was isolated firstly from the fungus Rhizoctonia leguminicola, which possesses immunomodulatory and antitumor properties, while as its analogues have provoked extensive research in the past 30 years.The research for marine natural products has become highlight of natural products chemistry research for almost half a century. Because of the extensive activity of marine natural products, their complex structure, and low content, access to marine natural products only from nature can not meet the needs for pharmacological further research any longer. Therefore, the asymmetric synthesis of marine natural products have become one of the most important fields on organic synthesis research. Research on analogues of natural products like swainsonine, its key intermediates and the relative analytic methods was displayed in this thesis, and main results was showed as followed:Firstly, we synthesized the ketone 2-80 over 6 steps on the basis of the key intermediate 2-64, which was derived from D-glutamic acid by our group's method, developed a highly selective (dr=95:5) reduction method for alcohol 2-81, from 2-80 by using Li(t-BuO)3AlH, and then established a new method for total synthesis of the (-)-8a-ePi-Swainsonine possessing diversified important activites from cheap D-glutamic acid. Thalassospiramides A and B were isolated from a new member of the marine a-proteobacterium Thalassospira in 2008. These two new cyclic peptides bear unusual y-amino acids show immunosuppressive activity in an interleukin-5 production inhibition assay (IC50=5μM for thalassospiramide B). Next, we established the synthetic methods for three key units of 12-membered skeleton of marine natural products Thalassospiramides A or B from L-Tyr, L-Val and L-Ser respectively. The N-methylation on L-Tyr was constructed successfully and provided compound 3-16 with high yields. In the meantime, we obtained the hydroxymethyl-amino alcohol through E-olefin 3-37. In addition, the synthesis of lactam 3-41 was explored through using DCC as a condensation reagent or under Yamaguchi conditions, which lay the foundation for the further asymmetric synthesis of the relative molecules.