脂蛋白脂酶激活剂艾溴利平类似物的合成

Synthesis of Lipoprotein Lipase Activator Ibrolipim Analogs

合成了两个新型的艾溴利平类似物——N-2-硝基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰肼(5,总收率28.1%)和N-2-四氮唑基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰胺(7,总收率30.5%)。以对氯甲基苯甲酸为原料,经酯化、水解和酰氯反应制得中间体4-[(膦酸二乙酯基)甲基]苯甲酰氯(4);4与2-硝基-4-氯苯肼盐酸盐反应合成了5。4先与2-氨基-5-氯苯腈反应制得N-2-氰基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰胺(6);6再与叠氮化钠反应合成了7。其结构经1H NMR和IR表征。

Two novel Ibrolipim analogs,diethyl 4-[2-（4-chloro-2-nitrophenyl）hydrazinecarbonyl]benzylphosphonate（5） with 28.1% total yield and 4-{[4-chloro-2-（1H-tetrazol-5-yl）phenyl]carbamoyl}benzylphosphonate（7） with 30.5% total yield,were synthesized.The intermediate diethyl 4-（chlorocarbonyl）benzylphosphonate（4） was prepared by esterification,hydrolysis and chlorination reaction from 4-（chloromethyl）benzoic acid.5 was obtained by the reaction of 4 with（4-chloro-2-nitrophenyl）hydrazine hydrochloride.7 was obtained by the reaction of 4 with 2-amino-5-chlorobenzonitrile,and then reaction with sodium azide in toluene.The structures were characterized by 1H NMR and IR.