Synthesis Of Advanced Intermediate Of Annotinolide C And Chiral 3-Indole-Spirocyclic Compounds

More than 300 Lycopodium alkaloids and their analogs have been isolated and identified from the lycopodiaceae plants to date.Owing to the novel structure and potential biological activity,their synthetic research has been attracting the interest of the chemists.This dissertation briefly describes the separation,classification,physiological activity and the total synthesis of some lycopodium alkaloids.And then the synthetic study toward the Annotinolide C which was isolated in 2016 and has rigid polycyclic skeleton was discussed.Subsequently,the application of a variety of chiral metal/ligand complexes derived from spirocyclic pyrrolidine compounds by our group has been examined towards the asymmetric allylation/ cyclization of indole-3-hydrazones.This dissertation includes the following three chapters:Chapter 1.Research status of Lycopodine alkaloids is described in detail.The separation,biological activity and structural classification of the lycopodium alkaloids were mainly summarized.And then the research progress of the different strategies and methods in total synthesis of Lycopodine alkaloids with complex structure was presented.Chapter 2.The tetracyclic core structure of Annotinolide C was built up by 17 steps of chemical conversions from 2-piperidone which was cheap and easy to obtain.The key steps featured a tandem epoxidation/semipinacol rearrangement step to construct [6.5] spirocyclic ring and a tandem semireduction/lactonization step to form a five-membered lactone ring.Chapter 3.Cu(Ⅱ)-SPDO catalyzed synthesis of spirocarbamate oxindoles in high enantioselectivity was investigated.Research progress of chiral catalysts derived from azaspirocyclic compounds was summarized.The derivation design and application of the azaspirocyclic catalysts were briefly described.Then,by use of a series of spiropyrrolidine oxazole(SPDO)bidentate ligands to associate with divalent copper,we have achieved the optimal enantioselectivities(almost all examples had higher than 99.9% ee)for synthesis of spirocarbamate oxindoles.Also,this methodology as a key step was applied to the total synthesis of two bioactive molecules.