Studies On The Synthesis Of Erysotrine And Erythrinine

Erythrina alkaloids are one of the most effective ingredients of the plants genus Erythrina.From now on,more than one hundred kinds of these alkaloids have been isolated and reported from Erythrina plants.Biological activity experiments show that this type of alkaloid has a wide range of biological activities,such as anti-oxidant,anti-anxiety,anti-AIDS,anti-spasm,anti-inflammatory,anti-cancer,induce sleep,neuronal nicotinic acetylcholine receptor antagonism and other biological activities.Erythrina alkaloids have a typical 6,6,5,6 tetracyclic spiro skeleton,which is welcomed by chemists.However,most of this kind of products already obtained by thousands of total synthetic experiments in the literature are racemates,or the key intermediates still need to be separated from diastereomers.There are few methods for the asymmetric synthesis of erythrina alkaloids,so the asymmetric synthesis of erythrina alkaloids is particularly critical.This article is divided into three chapters.In the first chapter,we introduced the construction of the spiro ring in detail.Such as general spiro ring,N heterospiro ring,and N,O heterospiro ring’s construction methods,in the second section we introduced the research progress of the synthesis of Erythrina alkaloids in recent years.The second chapter is divided into two parts.In the first part,we improved the synthesis of key intermediates based on the preliminary work of our group,optimized the reaction conditions,and increased the yield.The optimal conditions of the catalyst were further screened,and the absolute configurations of key intermediates 2-4 and 4-7were obtained.The ee values were all above 80%,and after recrystallization,it was greater than 95%.A large number of studies have been carried out on the construction of the double bond at the α position of the double carbonyl group.Experiments have shown that it is difficult to introduce the phenylselenyl group at the α position of the double carbonyl group due to excessive steric hindrance.Although phenylselenyl group can be introduced into the α-position of amide after decarboxylation,the yield is not high due to the steric hindrance of phenylselenyl group.After screening the reaction conditions,it is found that the method of introducing iodine and eliminating it can be used to form conjugated diene in one step,and then to olefin.A lot of attempts have been made on the oxidation of propionate sites,but the yield still needs to be improved.It is hoped to find an efficient method for introducing hydroxyl or carbonyl groups at allyl sites.Other steps can be carried out according to the relevant literature to complete the Erysotrine and Erythrinine alkaloids.’ fully synthesis,the later work is still under investigation.The second part of this article we from different substituents of phenylacetic acid,such as electron donating groups（4-Me,4-OMe,3,5-OMe,3,4,5-OMe）,electron withdrawing groups（3-F）and no substituents After acylation,reduction,re-acylation and deprotection,the ring-closure precursor phenolic compound is obtained.Then,under the oxidation of PIFA and other oxidants,to explore the universality of oxidative dearomatization-Michael ring-closure.The experimental results found that different substituents have a greater impact on this type of reaction,not all substituents can complete this type of reaction（only starting from 3,5-OMe and3,4,5-OMe substitutes’ phenylacetic acid.This type of reaction can be completed）.Based on the experimental results,we speculate that the reaction can only proceed when there is a sufficiently dense electron cloud on the benzene ring.Chapter 3 mainly states the experimental operation and the NMR datas of the compounds.