Department of Basic and Applied Sciences, GD Goenka University, Gurgaon, India.
Institut für Chemie, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.
Biomed Chromatogr. 2021 Jan;35(1):e4990. doi: 10.1002/bmc.4990. Epub 2020 Oct 21.
Of the various methods available for high-performance liquid chromatography separation of enantiomers (of e.g. amino acids and amino group containing compounds) by the pre-column derivatization approach, use of Marfey's reagent has been most successful with continued application since its introduction in 1984. The reagent is prepared from difluoro dinitro benzene by nucleophilic substitution of one of its F atoms by l-alanine amide. There is flexibility to prepare several chiral variants (by substituting the F atom with different chiral auxiliaries) and to tailor the hydrophobicity and resolution, ultimately, of the diastereomeric derivatives. The present paper assesses and reviews applications of Marfey's reagent and its chiral variants (i.e. other FDNP reagents) for enantioseparation of certain amino group containing drugs/amino acids, and to provide some case studies on enantiomeric separations that are important for the pharmaceutical industry. Various explanations for separation mechanism and elution order using FDNP reagents are included and the question of the configuration of the corresponding enantiomer using an indirect approach has also been addressed.
对于通过柱前衍生化方法对映异构体（例如氨基酸和含氨基的化合物）进行高效液相色谱分离的各种方法中，自 1984 年引入以来，Marfey 试剂的使用最为成功，并持续得到应用。该试剂是通过其一个 F 原子的亲核取代由二氟二硝基苯与 L-丙氨酸酰胺制备的。可以灵活制备几种手性变体（通过用不同的手性助剂取代 F 原子），并最终调整非对映异构体衍生物的疏水性和分辨率。本文评估和回顾了 Marfey 试剂及其手性变体（即其他 FDNP 试剂）在某些含氨基药物/氨基酸的对映体分离中的应用，并提供了一些对制药行业很重要的对映体分离的案例研究。包括了使用 FDNP 试剂的分离机制和洗脱顺序的各种解释，并且还解决了使用间接方法确定相应对映异构体构型的问题。
