可透皮吸收的白藜芦醇月桂酸单酯的合成与纯化

Synthesis and purification of transdermal absorbable resveratrol lauric acid monoester

以白藜芦醇(Res)、月桂酰氯(LC)为原料,在催化剂4-二甲氨基吡啶(DMAP)的作用下,合成白藜芦醇月桂酸酯。实验结果指出:白藜芦醇与月桂酰氯摩尔比为0.8、催化剂为白藜芦醇质量的5%、pH值为11、反应时间为4 h为合成白藜芦醇月桂酸酯的最佳工艺。因素Res/LC摩尔比对白藜芦醇的转化率影响极显著,催化剂添加量和反应体系pH值为较显著。以半制备高效液相色谱分离纯化白藜芦醇月桂酸单酯的条件为:C18柱;检测波长:306nm;柱温:25℃;进样量:18mL;流速:18mL·min^(-1);时间程序:0～30min,甲醇/水(mL·mL^(-1))由50∶50梯度变化至70∶30,30～45min,甲醇与水体积比恒定为70∶30;将半制备分离物进行无水甲醇重结晶,纯度达99.3%。LC-MS、~1H NMR分析表明:该合成物为白藜芦醇月桂酸单酯。透皮实验结果指出:白藜芦醇月桂酸单酯在0.5 h内可全部透过皮肤。

Resveratrol lauric acid ester was synthesized from resveratrol(Res)and lauroyl chloride(LC)in the presence of 4-dimethylaminopyridine(DMAP)catalyst.The experimental results show that the best process for synthesizing resveratrol lauric acid ester is that the molar ratio of resveratrol to lauryl chloride is 0.8,pH is 11,the catalyst was 5%of the resveratrol and the reaction time is 4 hours.The conversion of resveratrol was significantly influenced by the molar ratio of Res/LC,the addition of catalyst and the pH value of reaction system were significant.The separation and purification of resveratrol lauric acid monoester by semi-preparative high performance liquid chromatography was carried out on the column of:C18;detection wavelength:306nm;column temperature:25℃;sample volume:18mL;flow rate:18mL·min ^-1;time program:0~30min;methanol/water(mL·mL ^-1 )gradient changed from 50∶50 to 70∶30,30~45min,the volume ratio of methanol to water was constant to 70∶30;the semi-prepared separation was recrystallized with anhydrous methanol.The purity of the compound was 99.3%.LC-MS and 1H NMR analysis showed that the compound was a monoester of resveratrol lauricacid.The results of transdermal experiments indicate that resveratrol monolaurate could penetrate the skin completely within 2 hours.