米格列奈的合成工艺研究

Study on synthetic technology of mitiglinide

双(2S)-2-苄基-3-(cis-六氢异吲哚啉-2-羰基)-丙酸一钙二水合物(米格列奈)是日本2004年上市的新型口服降血糖药,其临床表现优异。本文研究建立一种以丁二酸二甲酯为起始原料、经Stobble缩合等反应合成米格列奈的工艺,并对其进行了优化,总收率为8.0%。关键中间体和产品结构均经1H-NMR1、3C-NMR等数据对其结构进行表征,所测定旋光值与文献值吻合。

（＋）-Monocalcium bis [（2S）-2-benzyl-3-（cis-hexahydroisoindolin-2-ylcarbonyl）-propionate] dehydrate （viz. Mitiglinide） is a noval oral hypoglycemic agent firstly marketed in Japan in year 2004. Its clinical manifestation is excellent. In this paper the synthetic route of MTL is established with dimethyl succinate as a starting material and through Stobble condensation. After conditions optimized the total yield can be 8.0%. The key intermediates and MTL are all characterized by ^1H-NMR and ^13C-NMR spectra and optical rotation value is measured and identical with the literature.