4-烃基-3-氰基-双环笼状磷酸酯类化合物的合成及生物活性研究

以2-烃基-2-羟甲基-1,3-丙二醇为原料, 经保护两个羟基, PCC氧化, 引入氰基, 脱保护后与POCl3或PSCl3环合, 成功合成了14个4-烃基-3-氰基双环笼状磷酸酯类化合物, 目标化合物的结构通过1H NMR, MS和元素分析进行了表征. 采用放射性配体受体结合实验, 测定了14个化合物抑制3H]EBOB 4’-ethynyl-4-n-propylbicycloorthobenzoate]与家蝇及大鼠GABA受体的结合活性. 结果表明部分化合物在10－5 mol/L具有较好的抑制活性, 且在大鼠与家蝇GABA受体之间具有一定选择性.

Synthesis and Bioactivity of 4-Alkyl-3-cyano-caged Bicyclic-phosphates

Fourteen 4-alkyl-3-cyano-caged bicyclic-phosphates were synthesized from 2-alkyl-2-hy- droxymethyl-1,3-propanediols via protection of the two hydroxyl groups, oxidation of the other hydroxyl group with PCC, introduction of the CN group, deprotection and cyclization with POCl3 or PSCl3. All target compounds were confirmed by 1H NMR, MS spectra and elemental analysis. In addition, the 14 compounds were examined for their inhibition of 3H]EBOB 4’-ethynyl-4-n-propylbicycloorthobenzoate] binding to housefly and rat GABA receptors and the results show that some of these compounds have inhibiting activity and selectivity between the rat and housefly GABA receptors at 10－5 mol/L.