姜黄素-4-芳杂环叉基衍生物合成及其油水分配系数的测定  

Synthesis of 4-Heteroarylene Derivatives of Curcumin and Determination of Their Oil-Water Partition Coefficient

作　　者：黄仰彤 齐心怡 邓思亮 谭祥颖 王涛[1] 曾丽云[1] 曹骋[1] 朱丽萍 HUANG Yangtong;QI Xinyi;DENG Siliang;TAN Xiangying;WANG Tao;ZENG Liyun;CAO Cheng;ZHU Liping(Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China)

机构地区：[1]广州中医药大学,广东广州510006

出　　处：《中药新药与临床药理》2024年第9期1408-1412,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广州中医药大学“双一流”与高水平大学建设项目(2021xk87,[2022]97号);国家自然科学基金项目(81774193)。

摘　　要：目的合成姜黄素Knoevenagel衍生物并测定其油水分配系数,为该类衍生物的进一步研究提供依据。方法以母体亚甲基为修饰位点,通过Knoevenagel缩合反应合成两个姜黄素衍生物4-(2-噻吩叉基)(3a)和4-(4-吡啶叉基)(3b),目标产物结构经核磁共振(NMR),红外吸收光谱(IR)、高分辨液质联用(HRLC-MS)确定,并通过高效液相色谱(HPLC)法测定3a和3b在正辛醇-水溶液中的油水分配系数。结果成功合成姜黄素Knoevengel衍生物3a和3b,两者的油水分配系数(lgPap)分别为0.96和0.82,与姜黄素(lgPap=3.85)相比,其水溶性更好。结论相较于姜黄素,姜黄素Knoevenagel衍生物的水溶性增加,可为芳杂环叉基结构修饰提高姜黄素的生物利用度和药理活性提供实验依据。Objective In this study,Knoevenagel derivatives of curcumin were synthesized,and their oil-water partition coefficient were determined.Our aim is to provide an experimental basis for further development of curcumin derivatives.Methods Two Knoevenagel derivatives of curcumin,including 4-(thiophen-2-ylidene)curcumin(3a)and 4-(pyridine-4-ylidene)curcumin(3b),were obtained by using the methylene group of curcumin as the modification site and purified by column chromatography.The structures of these derivatives were confirmed by nuclear magnetic resonance spectroscopy(NMR),infrared(IR)and high-resolution liquid mass spectrometry(HRLC-MS).The oil-water partition coefficient of the derivatives in n-octanol aqueous solution was determined by quantitative analysis using HPLC.Results Knoevenagel derivatives of curcumin were successfully synthesis.The oilwater partition coefficients(lgPap)of curcumin derivatives 3a and 3b are 0.96 and 0.82,respectively.Compared with the oil-water partition coefficient of curcumin(lgPap=3.85),it suggested that curcumin derivatives showed better water solubility than curcumin.Conclusion Compared to the curcumin prototype,Knoevenagel derivatives of curcumin increased water solubility and improved bioavailability.Thus,it may provide experimental basis for introducing heteroarylene moiety of the methylene position of curcumin to enhance pharmacological activity.

关 键 词：姜黄素衍生物 KNOEVENAGEL缩合反应 高效液相色谱法 油水分配系数 生物利用度 

分 类 号：R914.5[医药卫生—药物化学]