High Efficient Synthesis Of Complex Polycyclic Molecules

Natural products with a broad range of interesting biological activities,which render them and their derivatives valuable candidates for drug discovery have been widely used in daily life.However,their complex structures which contain polycyclic frameworks and multi consecutive chiral centers,impose great challenge for synthetic chemists.In this dissertation,based on the characteristics of polycyclic molecules,we use the intramolecular[2+2]cyclization reaction of eneallenone,intramolecular Michael addition of allenone and imininium-initiated asymmetric polyene cyclization to construct polycyclic structures.The main research contents are as follows:?1?Intramolecular catalysis of allenone and olefin by screening various chiral acids[2+2]cycloaddition reaction and finally found when the ring closure products in Bi?OTf?₃catalyst and Box,the ee can reach 78%.Then we will expand to contact the reaction of allenones and olefin reaction to construct fused four membered ring skeleton and we found that this reaction can build[6,4,5],[6,4,6]fused four membered ring by one step.Finally we used this reaction to complete the synthesis of the key intermediates of Italicene.?2?Through the screening of various acid catalyzed containing thiophene ring linked allenones intramolecular Michael addition,found Fe?OTf?₃ in 20%catalytic amounts and nitromethane as solvent at room temperature to yield 85%and obtain seven membered ring thiophene compounds,then expand to various substrates of seven membered ring and heterocyclic structure and finally this method as a key step to synthesis of natural product Frondosin B,complete the total synthesis of Frodosin B.?3?The use of chiral phosphine imide as a catalyst,imine initiator-initiated asymmetric polyene cyclization as a key step only 12-step reaction from the cheap,readily available achiral raw materials to complete the important activity of Chinese medicine Salvia Catalytic asymmetric total synthesis of the enantiomer of?-?-Ferruginol,a substance called poloxamer?also known as rust alcohol?.