D(-)-二吡啶甲基酒石酸酰胺在不对称氧化合成埃索美拉唑中的应用

Application of D(-)-Di-pyridylmethyl Tartaric Acid Amide in the Synthesis of Esomeprazole through Asymmetric Oxidation

D(-)-酒石酸二乙酯(1)分别与2-氨甲基吡啶和4-氨甲基吡啶反应,合成了D(-)-二吡啶甲基酒石酸酰胺2和3.分别以1～3为手性配体与钛酸异丙酯配合,催化过氧化氢异丙苯(CHP)不对称氧化埃索美拉唑前体(Eso-I)合成埃索美拉唑.结果表明,由配体2或3构成的催化体系在埃索美拉唑合成上显示出较高的催化活性和对映选择性.例如,当以2为配体,甲苯为溶剂,在优化的条件下进行反应时,Eso-I的转化率达84.7%,埃索美拉唑的选择性达91.8%,对映体过量值达89.0%.

Two di-pyridylmethyl D（-）-tartaric acid amides 2 and 3 were respectively prepared through the reaction of（-）-diethyl D-tartrate（1） with 2-aminomethyl pyridine and 4-aminomethyl pyridine.The compounds 1,2 and 3 coordinated with isopropyl titanate,respectively,were used as catalyst in the asymmetric oxidation of the precursor（Eso-I） of esomeprazole with cumene hydroperoxide（CHP） as oxidant.The results revealed that both the catalytic systems derived from ligand 2 and 3 and isopropyl titanate showed good catalytic activity and enantioselectivity in the synthesis of esomeprazole.For example,the conversion of Eso-I,the selectivity toward to the esomeprazole and the enantio excess reached 84.7%,91.8% and 89.0%,respectively,when 2 was used as the ligand and the reaction was conducted in toluene under the optimized conditions.