具有肝靶向潜力的甘草次酸酯和酰胺类衍生物的合成研究

Chemical synthesis of glycyrrhetinic acid ester and amide derivatives with liver targeting potential

目的利用甘草次酸的肝靶向特征,对3位、11位、18位和30位进行结构修饰,合成制备具有肝靶向潜能的甘草次酸酯和酰胺类衍生物,并进行结构表征。方法以18β-甘草次酸为先导化合物,对C3-位和C30-位酯化或酰胺化、C11-位脱氧及C18β-H的构型转化等化学修饰,制备甘草次酸酯类、酰胺类和11-脱氧衍生物;利用光谱方法进行结构表征。结果合成制备14种甘草次酸类衍生物;对理化性质和光谱特征进行详细描述,优化了制备工艺。结论甘草次酸酯和酰胺类衍生物的制备在甘草三萜类骨架的化学修饰研究及肝靶向载体特征的研究中以及新型小分子载体介导的肝靶向抗癌药物设计中具有一定的参考价值。

Objective To perform the chemical modification of carbon 3, 11, 18 and 30 positions of 18β-gly- cyrrhetinic acid （1813-GA） for optimizing its liver targeting potency, and to elucidate the structural eharacteristics. Methods The methods of modification include the esterification or amidation of C3-OH and C30-COOH groups; deoxification of Cll-keton group; optical conversion of 18β-H configuration, for preparing series of ester and amid derivatives, and for structural characterization. Results 14 glycyrrhetinic acid de rivatives were synthesized with optimized preparation process; their spectrometric characteristics and phys ieo-chemical properties were described systematically. Conclusion This works may have reference values for the progressive chemical modification of licorice triterpenoid skeleton and for studying new liver targeting drug carriers, as well as for designing small molecule carrier-mediated hepatic targeting anticancer drug candidates.