11-羟基甘草萜醇衍生物的制备工艺研究

Preparation Technology of 11-Hydroxylic Glycyrrhetol Derivatives

目的:对甘草次酸(Ⅰ)经还原修饰得到11-羟基甘草萜醇类衍生物,并考察制备工艺条件。方法:以化合物(Ⅰ)为原料,利用Red-Al和四氢铝锂等两种还原剂对C11-羰基和C30-羧基进行选择性还原,并利用简单的单因素分析法考察反应温度和时间对反应产率和分离纯化效果的影响。结果:通过还原反应获得11-羟基甘草萜醇类两种光学异构体18β-Olean-12-ene-3β,11α,30-triol(Ⅱ)和18β-Olean-12-ene-3β,11β,30-triol(Ⅲ),并进行光谱鉴定。2种还原方法结果表明,利用Red-Al还原化合物(Ⅰ)时,最佳反应条件为60℃/1 h,产率87%;利用四氢铝锂还原(Ⅰ)时,最佳反应条件为60℃/2 h,产率52%。结论:还原剂Red-Al和四氢铝锂在甘草次酸C11-羰基和C30-羧基的选择性还原中具有重要意义,其中利用Red-Al对甘草次酸进行还原修饰要比用四氢锂铝容易、产率高。

Objective： To prepare l l-hydroxylic derivatives of glycyrrhetol from glycyrrhetinic acid （compound Ⅰ ） and to investigate the preparation technology. Methods： Two chemical reductants, Red-Al and lithium aluminum hydrate were used for the selective chemical reduction of C11-keto and C30-carboxyl groups of compound （ Ⅰ ）. A simple single factor analysis was performed for investigating the impact of the reaction temperature and the reaction time towards the production yield and separation purification process. Results： Two optical isomers-18β-Olean 12-ene-3β, 11α, 30-triol （ Ⅱ ） and 18β-Olean-12-ene-3β, 11β,30-triol（Ⅲ）were obtained by the reaction of selective reduction, and their chemical structures were elucidated. The optimal conditions for the reaction by Red-A1 were 60℃/1h, product yield was 87%; and the conditions for reaction by lithium aluminum hydrate were 60℃/2h, product yield was 52%. Conclusion： Our results suggest that the use of reductants Red-Al and lithium aluminum hydrate has an important value for the selective chemical reduction of C11-keto and C30-carboxil groups of glycyrrhetinic acid （corn poun Ⅰ ）, in which the use of reductant Red-Al for reductive modification of compoun Ⅰ is more effective and productive than the use of lithium aluminum hydrate.