The Divergent Synthesis Of The Anti-cancer Activity(-)-Preussins And Its Analogues

New methods and technology of organic synthesis with high efficiency and selectivity isone of the core content of modern organic chemistry, but diversity synthesis as importantactive natural products core framework oriented is the end result of organic chemicalsynthesis. With the development of modern science and technology, especially the rapiddevelopment of biosynthesis Technology, the strategies of traditional organic synthesishave been deeply printed on the brand of the times. However, it does not meet to furtherreveal the biological study of the interaction between small molecules and biologicalmacromolecules. Therefore, based on inheriting and developing natural products related totheir structure determination and new synthetic methods, the newly developed synthesis ofdiversity oriented natural products with activity is still an important source of new drugresearch, has important meaning to further reveal the interactive mechanism in life betweenthe small molecule and major diseases. In this thesis, malic acid used as a cheap raw material,a new method was developed for the asymmetric synthesis of a versatile synthetic buildingblocks and diversity synthesis of key fragments of natural products, and used in the diversitysynthesis of heterocyclic alkaloids containing nitrogen with the important biological activities,which including three chapters,Chapter1: cheap D-malic acid used as starting material, the addition of β-aminoaldimine120and Grignard reagents was studied and compounds126a~o (dr from82:18to99:1) were prepared, which can be used in the diversity synthesis of natural productsTubulysins. Then, compounds126a~o were used as the precursor materials, a new syntheticmethod with high efficiency and selectivity was developed for the prepare5-substituted3-hydroxyl lactams1a~m bulding blocks by Sarret oxidation. Chapter2: the diversity synthesis of (+)-preussin2was explored by using5-substituted3-hydroxy1as building blocks, the (+)-preussin-ent115and its analogues138,139,140weresynthesized with high efficiency and selectivity (dr>99:1).Chapter3: on the basis of research in our group, we modified previous work andestablished a highly selective reduction reaction induced by chiral tert butyl sulfonamide. It isa new method to constitute the Tubulysins key fragment with aryl substituted groups based onstereochemistry (dr>99:1), which laid a foundation for the further study of Tubulysinsdiversity synthesis.