Lipka-Belloli E, Guelzim A, Yous S, Lefebvre J, Descamps-Francois C, Capet F, Vaccher C
Laboratoire de Chimie Analytique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de LILLE 2-BP 83-3, Lille Cédex France.
Chirality. 2001 May 5;13(4):199-206. doi: 10.1002/chir.1020.
In order to obtain milligram amounts of the enantiomers of tetrahydronaphthalenic derivative 5 to be tested for binding to the melatonin sites, preparative HPLC employed a mobile phase consisting of n-hexane-alcohol and a silica-based cellulose tris-methylbenzoate (Chiralcel OJ) using isocratic conditions and multiple repetitive injections. The preparative separation was optimized by adjusting the sample size from a scale-up of the analytical method. The enantiomeric elution order was reversed by the change from the carbamate type phase (Chiralcel OD-H) to the benzoate type phase (Chiralcel OJ) in analytical mode. The optical rotation and the circular dichroism spectra of the single enantiomers were determined after separation. The absolute stereochemistry of the two enantiomers of (+/-)-N-[2-(7-fluoro-1,2,3,4-tetrahydronaphthalen-1-yl)ethyl]acetamide 5 was established by X-ray crystallographic analysis. The purity obtained was sufficient for a first screen of their biochemical properties: the (-)-(S) enantiomer shows more affinity for melatonin receptors MT1, MT2 and is responsible of the selectivity towards MT2.
为了获得毫克量的用于检测与褪黑素位点结合的四氢萘衍生物5的对映体，制备型高效液相色谱采用由正己烷 - 醇组成的流动相和基于硅胶的三甲基苯甲酸纤维素（手性柱OJ），使用等度条件和多次重复进样。通过按比例放大分析方法来调整样品量，从而优化制备型分离。在分析模式下，从氨基甲酸酯型固定相（手性柱OD - H）转变为苯甲酸酯型固定相（手性柱OJ）时，对映体的洗脱顺序发生了反转。分离后测定了单一异构体的旋光度和圆二色光谱。通过X射线晶体学分析确定了(±)-N-[2-(7-氟-1,2,3,4-四氢萘-1-基)乙基]乙酰胺5的两种对映体的绝对立体化学结构。所获得的纯度足以对其生化特性进行初步筛选：(-)-(S)对映体对褪黑素受体MT1、MT2表现出更高的亲和力，并且是对MT2具有选择性的原因。
