乙酰胆碱酯酶抑制剂Territrem B类似物的合成新方法

The New Method for the Preparation of Territrem B Analogues as AChE Inhibitors

设计了一条新的2-烯-1-酮-类伊比林-20-基-取代苯甲酸酯(6)土震素(Territrem)B类似化合物的合成方法。以甲磺化伊比林醛(2)为原料,经脱甲磺酸生成2-烯类伊比林-13-醛(3),化合物3经溴代丁二酰亚胺(NBS)光照溴化一步法生成中间产物4,4不经分离直接与酚反应生成化合物5,5再经一步法水解氧化制得目标产物6。该方法不仅提高了6的收率(提高5%~30%),还合成了5个新化合物3和5b^5 e。生物活性测试表明,在10-4mol/L条件下,只有化合物6a对乙酰胆碱酯酶(AChE)显示出17%的抑制活性。

Some 2-en-1-one-ebelactonyl-20-yl-benzoyl esters as Territrem B analogues were prepared with new method. Aldehyde 2 was treated with Li2CO3 in N,N-dimethylacetamide （DMAc） to give 2-en-ebelactonyl-13-aldehyde 3 which was oxidation with N-bromosuccinimide （NBS） under irradiation gave the corresponding 2-en-1-bromo-acyl bromide 4 in one step. Then 4 was esterified directly with substituted phenols to afford the corresponding esters 5 in one step. And compound 6 can be prepared from 5 through hydrolysis and oxidation in one step. During these process, the yield of 6 was increased5% - 30% than the original method, and five new compounds 3 and 5b - 5e were prepared. Among all of the compounds only 6a showed 17% inhibitory activity to AChE in 10-4 mol/L.