Study On Asymmetric Michael Addition Reaction Based On The Synthesis Of Aizoaceae Alkaloid

The total synthesis of aizoaceae alkaloids has been a research hotspot and has received extensive attention because of its good anticancer and antimalarial biological activity.Our group has designed a new type of synthetic route,starting from inexpensive non-chiral substrates,and achieving asymmetric synthesis of the target compound(-)-Mesembrine through asymmetric catalytic reactions,avoiding the use of chiral raw materials.In the synthetic route,the construction of chiral carbon centers is the key to the synthesis of target compounds.This paper mainly focuses on the construction of chiral carbon centers and carries out the following work:Part ?:We reviewed the synthetic strategy of the target compound(-)-Mesembrine,introduced and analyzed the key asymmetric Michael addition reaction involved in the synthesis,and compared it with our synthetic strategy.Part ?:Asymmetric synthesis of target compound(-)-Mesembrine:(1)We performed a back-analysis of the target compound to determine the asymmetric synthesis route and raw materials for the asymmetric synthesis reaction;(2)Based on the asymmetric synthesis route,the substrates involved in the key asymmetric Michael addition reaction were synthesized and screened.(3)The chiral quinidine derivative catalysts involved in the reaction were synthesized and the reaction conditions were screened.The experimental results show that the catalysts have good catalytic effect(-58%ee,64%yield).However,the reaction takes a long time(t = 96 h);(4)According to the latest literature reports,chiral amines and thiotetramine-based chiral catalysts have been synthesized and their catalytic effects in asymmetric Michael addition reactions have been explored.The experimental results show that such catalysts shorten the critical reaction time and improve The yield(t = 36 h,70%yield)but the catalytic reaction has a lower stereoselectivity(-20%ee).Through the transformation and optimization of the substrate structure,the final research results show that the catalytic effect of the amine-based catalyst has been improved,and the experimental results are:-54%ee,54%yield,t = 36 h.Part ?:Experiments:(1)Raw material synthesis and data in key reactions;(2)Synthesis and data of a series of catalysts(Quinine pyridine derivatives,Cyclohexanediamines,Thioamide catalysts);(3)Conditional Optimization and Data of Asymmetric Michael Addition Reactions...