土震素B类似物的合成及其抑制乙酰胆碱酯酶作用的研究

 目的　探索土震素B结构类似物对乙酰胆碱酯酶抑制作用的构效关系。方法　以强效乙酰胆碱酯酶抑制剂土震素B为先导化合物 ,对天然产物酸枣仁皂苷元进行结构简化和改造 ,使其形成A/B环与土震素B一致的立体结构 ,并再引入土震素系列化合物中的芳基结构。用Elisa法测试了所合成的化合物对乙酰胆碱酯酶的抑制活性。结果　合成了两个系列的土震素B的类似物,其中化合物7c和15在10^-4mol·L^-1条件下分别显示出乙酰胆碱酯酶26%和32%的抑制活性。结论　初步探明了此类具有与土震素B的A/B环的立体化学一致的2-烯-1-酮A环结构以及含芳基酯基药效团的化合物对乙酰胆碱酯酶有一定的抑制活性。

Studies on the synthesis of territrem B analogues and its inhibitory effect on acetylcholinesterase

OBJECTIVE To investigate the structure-activity relationship on acetylcholinesterase inhibitory effect of territrem B analogues.METHODS The design and synthesis of A/B ring analogues of territrem B were carried out from jujubogenin 2a which was prepared from jujubogenin glycosides 2b obtained from the leaves of Zizyphus jujuba. The inhibitory activities on AChE of these synthetic analogues were examined.RESULTS Two series of territrem B analogues were prepared, 7c and 15 exhibited 26% and 32% inhibitory effect on AChE at 10^-4 mol·L^-1, respectively. CONCLUSION The A/B ring analogues of territrem B which possessed both of the 2-en-1-one and the aromatic ester moieties exhibited potential AChE inhibitory effect.