| Background:Amaryllidaceae plant have high ornamental value and are also a kind of very important medicinal plants.Their bulbs contain many chemical components such as alkaloids and non-alkaloids(such as polysaccharides,trace elements,flavonoids,etc.),and their alkaloids are the main medicinal components.Amaryllidaceae alkaloids(AAs)have unique biological activities due to their rich structure,such as anti-inflammatory,antiviral,antimalarial,acetylcholinesterase inhibition,antifungal and anti-inflammatory effects.Lycorine has the disadvantages of low natural content,limited natural resources,low extraction efficiency,large consumption of organic solvents and environmental hazards.Therefore,many chemists have been working on the total synthesis of lycorine.However,the synthesis methods and strategies of lycorine lack certain universality and practicability,so it is necessary to continuously develop more efficient methods to synthesize lycorine and its derivatives,and promote the development of drugs that can effectively treat diseases that seriously endanger human health.Based on this,this topic explores the synthesis of lycorine.Objective:With the aim of green chemistry,a highly efficient,simple,green and low-cost synthetic route of lycorine skeleton was found.Solve the problem of the source of lycorine,realize the small test,pilot test and industrial production,prepare a sufficient amount of lycorine compounds,and contribute to its pharmacological activity mechanism and pharmacokinetic research and other biological activity development.Methods:The bionic synthesis method design and experimental conditions of the core skeleton of lycorine were explored.Using tyramine as the starting substrate,key intermediates were obtained through oxidation,addition and other reactions,which involved several key links:organic catalysis N-hetero Michael addition reaction,Heck coupling reaction.In this process,the Heck coupling reaction was developed,and the conditions of the methodology were screened to lay the foundation for the subsequent preparation of the C ring of lycorine.This method is expected to be efficient and widely used in the synthesis strategy of lycorine.In this study,in order to synthesize the derivatives of lycorine and improve the pharmacological effect of lycorine,the fluorine oxygen atom(pharmacophore)was introduced into the structural fragment of lycorine,and the methodology of C-H bond fluoroalkoxylation of aromatic aldehydes was explored.Results:The methodology of Heck coupling reaction and the methodology of C-H bond activation were successfully established.Using the reaction conditions of the two methodologies,the compounds substituted by electron-withdrawing and electron-donating groups can participate in the reaction,and the product yield is from medium to high,which can be prepared in gram scale.The skeleton structure of lycorine was not synthesized,but the key intermediate of lycorine has been obtained.This synthetic route is simple,easy to operate and has high atomic utilization.Conclusion:In this paper,the key intermediate of lycorine was synthesized by biomimetic synthesis strategy,and the construction of lycorine skeleton was to be completed.The Heck coupling reaction methodology established in this paper has the advantages of simple conditions,low cost,environmental protection and efficient synthesis,and is expected to be applied to the synthesis strategy of lycorine and other drug molecules,the advantages of efficient activation and high selectivity of C-H bonds have become a good and common route for the synthesis of natural products.The construction of this methodology can pave the way for the synthesis of lycorine derivatives and other natural products.There are many studies on the synthesis of lycorine,but it lacks certain practicability and often causes environmental pollution.Therefore,the synthesis of lycorine by efficient,concise and environmentally friendly strategies is still a problem to be solved. |
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