Department of Chemical and Biological Engineering, Illinois Institute of Technology, 10 W. 33rd St. Chicago, Illinois 60616, USA.
J Pharm Sci. 2010 Sep;99(9):3931-40. doi: 10.1002/jps.22237.
Chiral drugs are a subgroup of drug substances that contain one or more chiral centers. For reasons of safety and efficacy, the pure enantiomer is usually preferred over the racemate in many marketed dosage forms. Thus, resolution of racemic mixtures is an active area of research. In this work, chiral self assembled monolayers (SAMs) on gold were employed as resolving auxiliaries in the crystallization of the amino acid valine. Results showed the ability to obtain one enantiomer in excess on the crystals grown on the chiral SAMs when starting with racemic solutions. The enantiomer obtained in excess was the one having opposite chirality to the monolayer being used. In addition, it was possible to obtain crystals of the pure enantiomer when starting with a solution having an enantiomeric excess value of 50%. Control experiments carried out without chiral SAMs showed that at equilibrium, mixtures of the pure enantiomer and racemic compound were obtained under these conditions. The enantiomer obtained on the chiral SAMs was the one that was initially present in excess regardless of the chirality of the monolayer being used.
手性药物是药物物质的一个亚组,其中包含一个或多个手性中心。出于安全和疗效的原因,在许多市售剂型中,通常优选纯对映异构体而非外消旋混合物。因此,外消旋混合物的拆分是一个活跃的研究领域。在这项工作中,金上的手性自组装单层 (SAM) 被用作结晶氨基酸缬氨酸的拆分助剂。结果表明,当从外消旋溶液开始时,在手性 SAM 上生长的晶体中可以获得过量的一种对映体。获得的过量对映体是与所用单层相反的对映体。此外,当从对映体过量值为 50%的溶液开始时,有可能获得纯对映体的晶体。没有手性 SAM 的对照实验表明,在这些条件下,在平衡时,获得了纯对映体和外消旋化合物的混合物。在手性 SAM 上获得的对映体是无论使用的单层的手性如何,最初过量存在的对映体。