Studies On The Constructing The Skeleton And Asymmetric Synthesis Of Lycorine

Lycorine-type alkaloids are a class of natural products with wide distribution and high content. Research shows that they display rich biological properties, such as antitumor, inhibiting acetylcholinesterase, antiviral, anti-inflammatory, anti-malaria and cardiovascular protection. The alkaloids have complex structure skeletons, often with multiple chiral centers and groups besides the galanthan ring system. Lycorine and fortucine are representatives of this kind of natural products and their total synthesis have been reported but most synthetic route involved a lot of complex reactions. In this thesis we intend to find out the more efficient and brief synthetic strategies in the synthesis of lycorine and fortucine in both skeleton and chiral centre constructions.In chapter1, the recent research progress in bio-activity studied and the progress in the total synthesis of Lycorine-type alkaloids were summarizes.In chapter2, our research about skeleton construction of Lycorine-type derivatives was described. We have prepared the key intermediate137with A ring, C ring and D ring through reductive amination reaction, oxidize by IBD and Michael reaction. On the other hand, we have also constructed the key intermediate184with A, C ring and desired chiral structures by D-Xylose.In chapter3, our studies on Fortucine synthesis were reported. We have obviously increased the reaction yield of aminocyclization and palladium catalyzed coupling by optimize the original route. We successfully obtained the intermediate198which have the desired skeleton and fuctional groups of Fortucine, but further investigations would be needed for last dehydration and TBS deprotection.Finally, we carried out a detailed statement of operation in experiment. The structures of all the intermediates as well as target compounds were confirmed by their NMR spectrascopy.