咖啡酸和灯盏乙素化学结构修饰.docVIP

咖啡酸衍生物的合成及其脑靶向性的研究 张静1，李标2，3，王欣，王毓杰1，李钰婷，张艺*1，罗维早* （1．成都中医药大学民族医药学院，611137；2．西南药业股份有限公司，400038；3．．重庆市中药研究院，400065） 咖啡酸衍生物的合成及其脑靶向性评价。以浓硫酸为催化剂，咖啡酸与甲醇和乙醇直接反应合成咖啡酸甲酯和乙酯，咖啡酸在磷酸催化下与醋酐酰化得3,4-二乙酰基咖啡酸；并测定了咖啡酸及其衍生物在正辛醇-磷酸盐缓冲溶液（pH7.4）系统中的分配系数；采用原代脑微血管内皮细胞（BMVEC）和星形胶质细胞（AC）共培养建立的体外血脑屏障模形来评价其脑靶向性。得到三个咖啡酸衍生物的油水分配系数均较咖啡酸高，亲脂性增强；其中咖啡酸甲酯和3,4-二乙酰基咖啡酸透过体外血脑屏障的能力较咖啡酸强。所合成的三个化合物经MS、1HNMR、IR和UV证实其结构；咖啡酸甲酯和3,4-二乙酰基咖啡酸能突破血脑屏障具有脑靶向性特点。 脑靶向；咖啡酸；血脑屏障 中图分类号：R914 文献标识码： 文章编号： Synthesis and brain targeted evaluation of derivatives of caffeic acid ZHANG Jing 1, LI Biao2, 3, WANG Xin4, WANG Yu-jie 1, LI Yu-ting4, ZHANG Yi1, LUO Wei-zao4* (1. Chengdu university of Traditional Chinese Medicine, Chengdu 611137, China; 2. Institute of pharmaceutical, Southwest Pharmacy Co. Ltd, Chongqing 400038, China; 3. Huaxi school of preclinical and forensic medicine 610041, China; 4. Chongqing Academy of Chinese Materia Medica, Chongqing 400065,China) Abstract: Objective Synthesis and brain targeted evaluation of derivatives of caffeic acid. Methods The ester derivatives of caffeic acid were obtained by esterification in the present of methanol and ethanol using sulfate acid as catalyst. 3,4-diacetyl caffeic acid was abtained by acetylation of caffeic acid catalyzed by phosphate acid. Their partition coefficient(P) in 1-octanol- phosphate buffer system(pH7.4) were also determined. And the in vitro BBB model coculture of brain capillary endothelial cells(BMVEC) with astrocytes(AC) of rat, was established for evaluating their brain target. Results The partition coefficients(P) of the three derivatives were much more lipophilic than that of caffeic acid. The potency of two of them, caffee methyl ester and 3,4-diacetyl-caffeic acid across the in vitro BBB are better than that of caffeic acid. Conclusion The three derivatives were the targeting compouds by MS, 1HNMR, IR, and UV spectra and two of them were potent brain target by evaluation of in vitro BBB model. Key Words: Brain target; Caf