乙酰胆碱酯酶抑制剂Territrem B 类似物的合成新方法

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~5e 。生物活性测试表明,在10-4 mol/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。

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

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 increased 5%~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.