Research On The Synthesis Of Azacyclic Skeletons And The Alkaloid(±)-Lupinine Via Intramolecular Cascade Cyclization Reactions

This paper mainly includes the following two parts:Part ?:Intramolecular cascade cyclization to construct azapolycyclic skeletonLycopodium is a type of alkaloid that exists in the pine pines fern pine and its relative huperaceae plants,with significant functions.The basic skeleton of stone pine alkaloids is mainly tricyclic or tetracyclic compounds composed of C₁₆N or C₁₆N₂.They can be divided into four types according to their structural characteristics.Among them,lycopodine alkaloids are most plentiful and discovered firstly;their remarkable biological activity and potential medicinal value have attracted wide interest of chemists.In 2008,Carter group completed the first enantioselective synthesis of lycopodine.However,the reports on the construction of the core skeleton of lycopodine,a nitrogen-containing tricycle,are very limited up to now.In this paper,we have designed a new route that utilizes the interconversion of acyliminium cations and enamides to achieve the efficient construction of its core skeleton.The key reaction conditions were screened and the optimal reaction conditions were established.Then under this condition,the universality of the substrate was studied,and a class of reaction methodology for the construction of azatricyclic and bicyclic was developed,and a series of good yield[6,6,6]cyclic azatricyclic compounds have achieved the synthesis of[5,6,6]and[7,6,6]fused azatricyclic compounds,and also completed the synthesis of important organic intermediates azabicyclic compounds.The structure of the product was identified by nuclear magnetic resonance and high-resolution mass spectrometry.Part ?:Study on the Synthesis of Alkaloid?±?-LupinineMany alkaloids containing a quinolizidine core have been found in nature widely.Among them,the alkaloid?±?-Lupinine,isolated from Lupin,is the most typical and has many important biological activities.The synthesis of this alkaloid is of great interest to chemists and many methods have been successfully achieved to date,however,the yield and synthesis efficiency of these reactions need to be improved.Thus,the development of efficient route for its synthesis still has good research value.In this paper,we used the above methodology to study the synthesis of?±?-Lupinine.The skeleton construction of?±?-Lupinine was successfully realized,but we encountered some difficulties in the functional groups transformation and failed to gain the target products.Further research is ongoing in our group.