Δ^5-3β，7β-二羟基甾醇和Δ^5-3β，7α-二羟基甾醇的立体选择合成及其对胆碱酯酶的抑制活性  

Stereo-synthesis and cholinesterase inhibitory activities of Δ5-3β,7β-dihydroxy sterols and Δ5-3β,7α-dihydroxy sterols

作　　者：陆伟刚[1] 张军[1] 苏镜娱[1] 曾陇梅[1] 

机构地区：[1]中山大学化学与化学工程学院,广东广州510275

出　　处：《中国药物化学杂志》2005年第4期202-206,i0001,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家高技术研究发展计划项目(863项目;2001AA624030);广东省自然科学基金博士科研启动项目(04300569);中山大学青年教师基金项目(1131002)

摘　　要：目的研究不同支链结构的Δ5-3β,7β-二羟基甾醇和Δ5-3β,7α-二羟基甾醇对胆碱酯酶的抑制活性.方法以3个不同支链结构的Δ5-3β-羟基甾醇为起始物,先乙酰化保护3β-羟基,再烯丙位氧化引入7-羰基,该羰基分别用NaBH4-CeCl3和L-selectride还原成不同取向的羟基,最后水解除去保护基得到6个不同支链结构的Δ5-3β,7β-二羟基甾醇和Δ5-3β,7α-二羟基甾醇,进而对目标化合物进行乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性实验.结果合成的6个化合物对乙酰胆碱酯酶无明显的抑制活性(IC50>100 μmol·L-1),对丁酰胆碱酯酶则有较强的抑制活性(IC50< 32 μmol·L-1),其中24-亚甲基胆甾-5-烯-3β,7α-二醇的抑制活性最强(IC50=9.5 μmol·L-1).结论 7位羟基的取向和不同的支链结构对化合物1～6发挥丁酰胆碱酯酶体外抑制活性有一定的影响.Aim To study the synthesis of Δ^5-3β，7β-dihydroxy sterots and Δ^5-3β，7α-starting from Δ^5-3β-hydroxy sterols with different side-chains and their inhibitory activities against cholinesterase. Methods Δ^5-3β，7β-Dihydroxy sterols and Δ^5-3β，7α-dihydroxy sterols were synthesized byallylic oxidation of Δ^5-steroids with PCC/Al2O3, followed by conversion of 7-keto to 7-hydroxy with NaBH4/CeCl3·7H2O or L-selectride as reducing agents, respectively. The structures of the target compounds were determined by comparing their physical constants and spectral data with those in literatures. Compounds 1 - 6 were tested for their inhibitory activities against acetylcholinesterase （ACHE） and butyrylcholinesterase （BuChE）. Results Compounds 1 - 6 show no evident inhibitory activities against AChE （IC50 〉100.0 μmol·L^-1）, but they all possess inhibiting potential in a concentration-dependent manner a-gainst BuChE （IC50 〈 32.0μmol· L^-1）. Among them, the most active compound is 24-methylenecholest-5- ene-3β, 7α-diol with an IC50 value of 9.5μmol· L^-1. Conclusion Orientation of 7-hydroxyl group and different side-chain of the title compounds are important to the BuChE inhibitory activities in vitro.

关 键 词：药物化学 化合物制备 化学合成 Δ^5-3β 7β-二羟基甾醇 Δ^5-3β 7α-二羟基甾醇 胆碱酯酶 

分 类 号：R914[医药卫生—药物化学]