高等学校化学学报
高等學校化學學報
고등학교화학학보
CHEMICAL JOURNAL OF CHINESE UNIVERSITIES
2014年
2期
292-296
,共5页
AG7088%光学纯度%手性高效液相色谱%X射线衍射
AG7088%光學純度%手性高效液相色譜%X射線衍射
AG7088%광학순도%수성고효액상색보%X사선연사
AG7088%Optical purity%Chiral HPLC%X-Ray diffraction
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。
在(2E,4S)-4-叔丁氧羰基氨基-5-[(3S)-2'-氧代-3'-吡咯烷基]-2-戊烯痠乙酯(1)已有立體選擇性閤成路線的基礎上,對各步產物的光學純度進行瞭嚴格的檢驗,研究瞭反應條件對這些產物光學純度的影響,併利用單晶X射線衍射方法確定瞭該類化閤物的絕對構型。
재(2E,4S)-4-숙정양탄기안기-5-[(3S)-2'-양대-3'-필각완기]-2-무희산을지(1)이유입체선택성합성로선적기출상,대각보산물적광학순도진행료엄격적검험,연구료반응조건대저사산물광학순도적영향,병이용단정X사선연사방법학정료해류화합물적절대구형。
(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 pro-tease 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 sol-ving the problems were provided. The molecular structure of intermediate product (2S)-2-( t-butoxycarbonyl-amino)-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.