Sinomenine Based Molecular Structure Modification Research

It has become an effective way for the world’s pharmacy created worker by findingactive compounds from natural products as lead compounds to create new drugs.Because natural products have low activity, undesirable pharmacokinetic, lowspecificity, toxic side effects and any other disadvantages, they can’t be directly used asmedicine, they need further structural transformation or modification.Sinomenine, a natural alkaloid extracted from Sinomenium acutum (Thunb.) Rehd.et Wils, has anti-inflammatory, immunosuppressive, analgesic sedation, anti-arrhythmia,drug detoxification and many other pharmacological effects. In clinic, the agentsincluding sinomenine hydrochloride injection and tablets, pills, capsules ware used inthe treatment of rheumatoid arthritis and other diseases. However the disadvantagesincluded instability and easy decomposition under light or heat, big drug dosage, shorthalf-life, slow drug effect in clinic, and strong histamine release produced skin rash,allergic shock, gastrointestinal reaction and other side effects. It was seriously hamperedwidely used in clinic.The full name of sinomenine is (9alpha,13alpha,14alpha)-7,8-Didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one. and its skeleton is composedby four rings, which ring A is a benzene ring, ring B is a half-chair six-memberedring connecting with ring A, ring C was a twist chair six-membered ring with α,β-unsaturated ketone structure, ring D was a six-membered nitrogen chair ring.The clinical instability of the structure comes mainly from its chemical instability.By the transformation of the structure of sinomenine may find a higher biologicalactivity, stable structure sinomenine derivatives.Therefore, in view of sinomenine has two active hydrogen, based on thestructure of sinomenine, we designed and synthesized eight sinomeninederivatives with benzene azo and acetyl, and the structures of all these newcompounds were confirmed by MS, IR,1H NMR and element analysis.(1)Seven new substituted benzene-azo sinomenine derivatives were designed andsynthesized by coupling reaction reaction of aniline and sodium nitrite with sinomeninehydrochloride.(2)a new substituted acetyl sinomenine derivatives were prepared by acylationreaction of sinomenine, pyrrolidine and chloride.The results of this research papers can help us with the further structuraltransformation of sinomenine.