Armstrong D W, Ward T J, Armstrong R D, Beesley T E
Science. 1986 May 30;232(4754):1132-5. doi: 10.1126/science.3704640.
For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.
对于许多药物而言，临床上仅可获得外消旋混合物。由于药物的不同立体异构体通常会引起不同的生理反应，使用纯异构体可能会产生更确切的治疗效果。研究了固定化β-环糊精对多种药物立体异构体的差异络合作用。观察到β-受体阻滞剂、钙通道阻滞剂、镇静催眠药、抗组胺药、抗惊厥药、利尿剂和合成阿片类药物等临床上有用类别中的多种化合物具有手性识别和外消旋拆分作用。还证明了具有心脏活性和抗疟疾作用的金鸡纳生物碱以及两种抗雌激素的非对映异构体的分离。比较了通过该技术拆分的普萘洛尔和未拆分的华法林与β-环糊精形成的复合物的三维投影。这些研究增进了对β-环糊精手性相互作用的理解和应用，并且展示了一种测量光学纯度以及分离或生产药物纯对映体的方法。此外，这种高度特异性的技术还可用于对映体药物的药理学评估。
