| As the important natural products,Lycorine alkaloids possess many physiological activities,mainly including antitumor,antiacetylcholinesterase,antiinflammation and so on.?-Lycorane,a representative of Lycorine alkaloids,has drawn extensive attention due to its unique pyrrolidine 4-ring structure.In this thesis,a novel synthetic route was designed to accomplish the total synthesis of(-)-?-Lycorane concisely and efficiently.Due to the unique chemical structure of natural product(-)-?-Lycorane,we focused on the construction of the B and D rings of four-membered rings structure in the design and synthesis of this target molecule.The full synthesis study was divided into the following three routes.The first route attempted to synthesize the target product through lithium halogen exchange and palladium-catalyzed coupling reactions in aryl halogen atoms.However,the synthetic route was hard to proceed owing to the existence of two adjacent halogen atoms.In the second synthetic route,intramolecular Heck coupling reaction was employed to establish the B ring,and the total synthesis of(±)-?-Lycorane and its regioisomer were successfully completed.But there is no regional selectivity,which was not consistent with our anticipated result to obtain the sole target product(±)-?-Lycorane.In the third synthetic route,with the help of the "occupied" bromine atoms,(±)-?-Lycorane and its regioisomer were selectively synthesized with a single region through the intramolecular Heck coupling reaction.We found that the bromine atoms could also be reductive in ‘onepot' approach in this palladium-catalyzed free radical Heck coupling reaction.Finally,the total synthesis of(-)-?-Lycorane was successfully accomplished through asymmetric synthesis.These synthetic strategies in the synthesis of the target molecule have the advantages of unique innovation and extensive practical application,which provide an important reference in the synthesis of other related Lycorine alkaloid compounds. |
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