(2E,4S)-4-叔丁氧羰基氨基-5-[(3S)-2'-氧代-3'-吡咯烷基]-2-戊烯酸乙酯的立体选择性合成及绝对构型

在(2E,4S)-4-叔丁氧羰基氨基-5-(3S)-2'-氧代-3'-吡咯烷基]-2-戊烯酸乙酯(1)已有立体选择性合成路线的基础上,对各步产物的光学纯度进行了严格的检验,研究了反应条件对这些产物光学纯度的影响,并利用单晶X射线衍射方法确定了该类化合物的绝对构型.

Stereo Selective Synthesis and Absolute Configuration Determination of (2E,4S)-4-(t-butoxycarbonylamino)-5-[(3S)-2’-oxo-3’-pyrrolidinyl] -2-pentenoic Acid Ethyl Ester

(2E,4S)-4-(t-Butoxycarbonylamino)-5-(3S)-2'-oxo-3'-pyrrolidinyl] -2-pentenoic acid ethyl ester(1) is a key intermediate widely used in drug candidate synthesis, such as the human rhinovious 3C protease inhibitor AG7088 and its related substances which are currently being developed for treatment of common cold, severe acute respiratory syndromes(SARS) and hand, foot, mouth disease(HFMD). Based on existing synthetic routes using L-glutamic acid as starting material, the optical purities of each intermediate product was rigorously examined, and the effects of reaction conditions on the optical purities of the products were studied in details. Meanwhile, racemic samples of each product were prepared from D,L-glutamic acids using the same procedures and used for comparison in high performance liquid chromatography(HPLC) analyses. Thus, new factors that could influence the optical purities of the final products were discovered, and methods for solving the problems were provided. The molecular structure of intermediate product (2S)-2-(t-butoxycarbonylamino)-3-(3S)-2'-oxo-3'-pyrrolidinyl] propanol(5) was determined by the X-ray diffraction method, which provides direct evidence for the absolute configuration of these products.