土震素B类似物中A环2-烯-1-酮结构的合成方法改进及衍生物抗脑缺血活性

Improved synthesis of 2-en-1-one moiety in the Aring of territrem B analogues and evaluation of their protective effect against brain ischemia injury

目的改进土震素B类似物A环 2 烯 1 酮结构的合成路线 ,研究所合成的衍生物对新生大鼠原代培养海马神经元细胞缺糖缺氧损伤的保护作用。方法以 2 烯 伊比林酯为原料、溴代丁二酰亚胺代替三氧化铬为氧化剂合成目标化合物 ,溴代副产物经水解、氧化也转化为目标化合物。以大鼠原代培养海马神经元细胞缺糖缺氧损伤模型测试所合成化合物的活性。结果与结论共合成 4个未见文献报道的新化合物 ,经1H NMR和MS确证其结构。体外试验表明 :化合物 6b对大鼠原代培养海马神经元细胞缺糖缺氧损伤有较强的保护作用。

Aim To improve the synthetic procedure of 2-en-1-one moiety in the A ring of territrem B analogues,and to evaluate their protective activities against OGD(oxygen-glucose deprivation)-induced injury of a primarily cultured newborn rat′s hippocampal neurons.Methods The target compounds were synthesized from 2-en-ebester 5 and partially transformed from the by-product of 2-en-1-bromo-ebester 8 via bromination,hydrolysis and oxidation.Their protective activities against injury of a primarily cultured newborn rat′s hippocampal neurons arising from OGD were determined.Results and conclusions Four derivatives of 2-en-1-one-ebester 6a～6d were synthesized with the structures confirmed by their 1H-NMR and MS spectra.The pharmacological data shows that compound 6b is active against injury arising from OGD.