Abstract

We determined that the absolute configuration of 5-[5-(1-methylethoxy)pyridin-2-yl]-5-methylimidazolidine-2,4-dione (hydantoin) is the (S)-form for the liver X receptor (LXR) β-selective agonist through X-ray crystal structure analysis of the hydantoin hydrogen bromide salt. Furthermore, we established a practical synthesis of the chiral hydantoin with 99% ee by the optical resolution of racemic methyl 2-amino-2-[5-(1-methylethoxy)pyridin-2-yl]propanoate with d-(–)-mandelic acid on a multi-kilogram scale. Finally, we improved the synthesis method of the LXR β-selective agonist.

We determined that the absolute configuration of 5-[5-(1-methylethoxy)pyridin-2-yl]-5-methylimidazolidine-2,4-dione (hydantoin) is the (S)-form for the liver X receptor (LXR) β-selective agonist through X-ray crystal structure analysis of the hydantoin hydrogen bromide salt. Furthermore, we established a practical synthesis of the chiral hydantoin with 99% ee by the optical resolution of racemic methyl 2-amino-2-[5-(1-methylethoxy)pyridin-2-yl]propanoate with d-(–)-mandelic acid on a multi-kilogram scale. Finally, we improved the synthesis method of the LXR β-selective agonist.

中文翻译：

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新型构型X受体β-选择性激动剂5- [5-（1-（甲基乙乙氧基）吡啶-2-基] -5-甲基咪唑烷-2,4-二酮的绝对构型的确定和实用手性合成

摘要

我们确定5- [5-（1-（甲基乙氧基）吡啶-2-基] -5-甲基咪唑烷-2,4-二酮（乙内酰脲）的绝对构型是肝脏X受体（LXR ）的（S）-形式乙内酰脲氢溴酸盐的X射线晶体结构分析，得出β选择性激动剂。此外，我们通过消旋2-氨基-2- [5-（1-（1-甲基乙氧基）吡啶-2-基]丙酸酯与d -（-）-的外消旋甲基丙烯酸的光学拆分，建立了具有99％ee的手性乙内酰脲的实用合成方法。多公斤级的扁桃酸。最后，我们改进了LXRβ选择性激动剂的合成方法。

我们确定5- [5-（1-（甲基乙氧基）吡啶-2-基] -5-甲基咪唑烷-2,4-二酮（乙内酰脲）的绝对构型是肝脏X受体（LXR ）的（S）-形式乙内酰脲氢溴酸盐的X射线晶体结构分析，得出β选择性激动剂。此外，我们通过消旋2-氨基-2- [5-（1-（1-甲基乙氧基）吡啶-2-基]丙酸酯与d -（-）-的外消旋甲基丙烯酸的光学拆分，建立了具有99％ee的手性乙内酰脲的实用合成方法。多公斤级的扁桃酸。最后，我们改进了LXRβ选择性激动剂的合成方法。