| As one of the effective components of traditional Chinese medicine,alkaloids have been an important research object for organic chemists and pharmacologists because of its unique chemical structure and good bioactivity.However,it is difficult to obtain enough substances for comprehensive pharmacological research only by isolation because some alkloids are very few in nature.Therefore,it is an effective way to solve this problem to obtain natural products by developing chemical synthesis method.In addition,chemical synthesis not only helps to confirm the structure of natural products,but also promotes the development of related synthesis methods.It is necessary to develop a synthesis method to construct its core skeleton quickly in view of the complex ring structure of natural products from both economic and environmental perspectives.The main content of this paper is to study the copper catalyzed formal [4+3] cycloaddition to construct the aza-[3,2,1] bridge cyclooctane skeleton of hosieines A-C.Hosieines A-C are a class of lupine alkaloids with aza-[3,2,1] bridge cyclooctane skeleton.Related studies have showed that these natural products have good affinity for neuronal nicotinic acetylcholine α4β2 receptor,which shows the potential application value of these compounds in the clinical treatment of central nervous system diseases.By analyzing the structure of hosieines A-C,we believe that the aza-[3,2,1] bridge cyclooctane skeleton can be constructed by the copper catalyzed formal [4+3] cycloaddition from aziridine and cyclopentadiene derivatives using the method developed by us.Our method has the advantages of simple preparation of the substrates,good reaction results,good compatibility with many substrates,and has a bright application prospect.This method not only lays a good foundation for the divergent total synthesis of hosieines A-C but also provides a new idea and method for the synthesis of other natural products containing this kind of skeleton. |
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