Synthesis Of Chuanhuning

Chuanhunig, Kalii dehydrographolidi succinas (DAS-K), is a derivative of andrographo1ide. It has thestructure of diterpene lactone and is a kind of antipyretic-analgesic and anti-inflammatory drug. Accordingto modern pharmacological research, Andrographolide and its derivatives not only have the effects ofanti-inflammatory sterilization, but have the potential effects of anti-HIV, anti-tumor and immune efficacyand immunobiological activity. For its strong efficacy, convenience of use and fewer side effects,Chuanhuning has replaced other traditional andrographolic drugs clinically. So it has great significance ofoptimize its synthetic process.In this paper, synthetic scheme of Chuanhuning was designed. Andrographolide and succinicanhydride were chosen as starting material, and the intermediate,14-deoxy-11,12-didehydroandrographolide succinate (DAS) was synthesized under water-free and oxygen-freeconditions with the solvent of pyridine. Then the reaction mixture was scattered to the acidic solution forcrystallization and purified with activated carbon. Chuanhuning was synthesized with the DAS andsaturated KHCO3.In the synthesis of DAS, the yield and purity were obviously increased in higher temperature and longreaction time conditions. There existed the transformation from single esterification products to doubleones through HPLC-MS monitoring. Crystallization step was optimized by replacing the water with HClsolution, and residual solvent in product was greatly reduced. The purity of refined DAS dealt withactivated carbon is superior to the traditional recrystallization method. The optimized condition of DAS-Kpreparation was selected with orthogonalizing methods. The effect of temperature to yield was also studiedOne-factor analysis of variance and orthogonalizing methods were intiated to optimize technologicalparameters and decided the main influential parameters. The improved process has the potential economicvalue of industrial production for its advantages of high yield, low cost and easy operating.The intermediate and final products are characterized by IR,1H-NMR and13C–NMR. The resultsshow that the structure of the synthetic compounds is consistent with that of the reference.