El-Behairy Mohammed Farrag, Hassan Rasha M, Abdallah Inas A
Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt.
Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza 12511, Egypt.
ACS Omega. 2021 Sep 23;6(39):25835-25841. doi: 10.1021/acsomega.1c04613. eCollection 2021 Oct 5.
Two commercialized polysaccharide-based chiral stationary phases, Lux cellulose-2 and Lux amylose-2, were examined for their chiral recognition ability on a set of 18 biologically active racemic 4,5-dihydro-1-pyrazole derivatives by applying normal and polar organic elution modes. The results showed that all compounds were baseline-resolved with at least one of the used elution modes. The cellulose-based column was superior using polar organic mobile-phase compositions with analysis times close to 5 min and resolutions up to 18, while the enantiomer-resolving ability of amylose-based columns was greater using the normal elution mode with analysis times close to 30 min and resolutions up to 30. The competition between the analytes and the mobile phase constituents on H-bond interactions with the stationary phase has been discussed, and the impact of this competition on chiral recognition has been investigated. It was found that the polar organic mode is very beneficial for short run times and sharp peaks. The developed enantioselective high-performance liquid chromatography (HPLC) methods will be applied to monitor the stereoselective synthesis of compounds or to develop preparative HPLC techniques for compounds , followed by stereospecific pharmacological studies for each enantiomer separately. Greenness profile assessment of the different elution solvents was carried out using the AGREE metric approach.
通过采用正相和极性有机洗脱模式，研究了两种商业化的基于多糖的手性固定相Lux纤维素-2和Lux直链淀粉-2对一组18种具有生物活性的外消旋4,5-二氢-1-吡唑衍生物的手性识别能力。结果表明，所有化合物在至少一种所用洗脱模式下均能实现基线分离。基于纤维素的色谱柱在使用极性有机流动相组成时表现更优，分析时间接近5分钟，分离度高达18，而基于直链淀粉的色谱柱在采用正相洗脱模式时对映体分离能力更强，分析时间接近30分钟，分离度高达30。讨论了分析物与流动相成分在与固定相的氢键相互作用上的竞争，并研究了这种竞争对手性识别的影响。发现极性有机模式对于短运行时间和尖锐峰形非常有利。所开发的对映体选择性高效液相色谱（HPLC）方法将用于监测化合物的立体选择性合成或开发化合物的制备型HPLC技术，随后分别对每个对映体进行立体特异性药理学研究。使用AGREE指标方法对不同洗脱溶剂的绿色度进行了评估。
