Preparation Of Licorice Active Components And Synthesis Of Liver Targeting Anticancer Pro-drugs From Glycyrrhetinic Acids As Carrier

Objective: To study the preparation techniques of triterpenoid glycyrrhetinic acid (GA) and flavonoid glabridin(GB) from Xinjiang licorice root; and on the bases of good hepatoma cells directing property of GA,we synthesized GA derivatives as the drug carriers , and coupled with the anticancer moiety of cyclophosphamide—dichloro-phosphoracyl nitrogen mustard (DPNM) for preparing anticancer prodrugs with the hep-directing potency; and to elucidate their chemical structures. Methods: We extracted and purified glycyrrhizin(GL)from Glycyrrhiza inflata bat., hydrolizited into 18β-GA; used 18β-GA as starting compound and prepared six semi-synthetic GA derivatives by the reaction of reduction and esterification; furthermore, we prepared 18α-GA from its configiration (18β-GA) by the reaction of optical isomeration; according to the chamical reactivity and stability , we choosed two derivatives--18α-MGA (18α-methy glycyrrhetinic acid) and 18β-MGA, combined with the anticancer moity-- DPNM for preparing new liver targeting prodrug and studied their physical-chemical properties and spectrometrical characteristics. We also prepared glabridin ( GB ) from Xinjiang Glycyrrhiza glabra by column chromatography and thin layer chromatography methods. Results: We obtained six GA derivatives (as carriers), two liver targeting pro-drug -18α-methy glycyrrhetinic acid - dichloro-phosphoracyl nitrogen mustard Ester (18α-MGA- DPNM) and 18β-methy glycyrrhetinic acid-dichloro-phosphoracyl nitrogen mustard ester (18β-MGA-DPNM) and one flavonoid conpound (glabridin) by above methods; studied their physical-chemical properties and spectrometrical characteristics. Conclusion: The prepared liver targeting drug carriers and pro-drug compounds provide a bases for further pharmacological screening of their biological activities. This study has an important value on the fondemental study of new targeting anticancer drugs and the in-depth research & development of Xinjiang licorice resources.