Exploration Of Catellani Ortho-acylation And Ipso-Alkynylation Reaction And Exploration Of The Total Synthetic Method Of Bufalin

Section 1.Exploration of Catelani ortho-acylation and ipso-alkynylation reactionThe Catellani reaction using palladium and norbornene as a combined catalyst is a coupling reaction capable of simultaneously constructing a plurality of carbon-carbon bonds on a benzene ring.It can easily construct multi-substituted aromatic derivatives and provide a better solution for the synthesis of organic compounds or natural products.Since the discovery of this reaction,a large number of research groups have studied it and expanded a number of ortho-reactive reagents and termination reagents.This paper classifies the reactions according to the different orthoreactive reagents,briefly introduces the research progress of Catellani reaction,and summarizes the application of the reaction in the total synthesis of natural products.2-Alkynyl aromatic ketones are key structural motifs in many functional materials and pharmaceutical agents,and are also significant scaffolds in the complex natural products.Previously discovered synthetic methods have some drawbacks.Actually,a practical synthesis of 2-alkynyl aromatic ketones with highly tolerant functional-group is still desirable.A palladiumcatalyzed and norbornene-mediated Catellani reaction was developed through ortho-acylation and ipso-alkynylation for the aryl iodides.Acyl chlorides were used as acylation reagents and phenylpropiolic acids were used as termination reagents respectively in this transformation.As a result,the reactivity of these three different compounds matched well and this unreported combination could be used extensively.Section 2.Exploration of the Total Synthetic Method of BufalinChansu is a valuable Chinese medicine with a history of thousands of years.It has been widely used in ancient times.It is collected from the epidermis of the Bufo bufo gargarizans Cantor and the Bufo melanostictus Schneider,which is animal secretion,toxic,and processed after use.Traditional Chinese medicine believes that it has the effects of detoxification,swelling,pain relief,refreshing,etc.After research by modern pharmaceutical technology,it has been found to have cardiotonic,anti-tumor,local anesthesia and other effects.After modern separation and analysis,it is confirmed that the ingredients in Chansu are complex.Because of this,it is difficult in determining the target of Bufalin,which also limits the application of Bufalin in some areas.Therefore,in recent years,more and more research has turned to the monomer components in this traditional medicine.Bufalin is an active ingredient in the Chansu and one of the highest content in it.It has a clear cardiac and anti-tumor activity,which has attracted the interest of chemical and pharmaceutical workers.However,its therapeutic window is very narrow and the medication is not safe.In response to this,some research groups have structurally modified it,hoping to obtain compounds with low toxicity and high activity,and also achieved some good results.The conventional source of Bufalin is extracted from Chansu,and its content in it is low,which leads to its lack of source,high prices,and the market is in short supply.Therefore,a cheap and mild synthetic route of Bufalin is very necessary.In the 1970s,some research groups constructed some routes of total synthesis study on it.However,these routes cannot be widely promoted due to expensive materials or harsh reaction conditions.In response to this problem,in this experiment,we plan to synthesize Bufalin with cheap materials(5 yuan per gram)and mild reaction conditions.It also lays a foundation for the structural modification of Bufalin from the increasing efficacy and decreasing toxicity.