Studies On The Synthesis Process And Quality Of Liguzinediol

Ligustrazine is an alkaloid monomer extractd from Chinese traditional medicine herb Chuanxiong(Ligusticum wallichii Franch),it has various pharmacological activities such as improving cerebral ischemia,vasodilation,anti-platelet-aggregation,anti-free-radical action,thrombosis prevention,heart protection and so on.Researches on the pharmacological activity of ligustrazine derivatives showed that liguzinediol has obvious positive inotropic effect on myocardium with no arrhythmia risk by acting on myocardium SERCA2a targets.The study of this article is mainly on the synthesis and quality of liguzinediol.The aim is to optimize the synthesis process,improve the operability and safety of the industrialization production;establish a effective method to control the quality of this raw material.1.Synthesis process of liguzinediolLiguzinediol was synthesized starting from ligustrazine through oxidation,Boekelheide rearrangment and hydrolysis.The optimized synthesis processes of liguzineidol are as follows:(1)the oxidizing reaction:N,N’-dioxiotetramethylpyzine refined using ethyl acetate as solvent in a good yield;(2)Boekelheide rearrangment reaction:selected the method of liquid feeding instead of solid feeding,molar ratio of acetic anhydrid to N,N’-dioxiotetramethylpyrazinee was 1:7,reaction temperature was 90 ℃,reaction time was 14 hours;(3)the hydrolysis reaction:the high yield was obtained when reaction time was 5 hours.The synthesis process was improved and the overall yield was increased.The products were purified by columnchromatography and crystallization.The purity was more than 99%.The overall yield was increased to 24.4%,and was 7.6%more than that of the original literature methods.2.Studies on quality of liguzinediolThe main contents include characters,melting point,solubility,identification,its related substances and assay.RP-HPLC has been developed to the determination of liguzinediol and its related substances:The chromatographic condition was analytical column(C18)thermostated at 30℃;the mobile phase was methanol-water(20:80)at the flow rate of 1.0 ml-min-1,and the detection wavelength was set at 278 nm.The result showed that this method has a good specificity.There was a good linear relationship in range of liguzinediol 60 μg·ml-1～140 μg·ml-1.The method is accurate,reliable and good reproducibility,which is applicable for control the quality of liguzinediol.