Department of Medicinal Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Dr. A. Jurasza 2, 85-089 Bydgoszcz, Poland.
Department of Biomedical Chemistry and Polymer Science, Faculty of Chemistry, Nicolaus Copernicus University in Torun, Gagarina 7, 87-100 Toruń, Poland.
Int J Mol Sci. 2023 Jul 5;24(13):11124. doi: 10.3390/ijms241311124.
Clopidogrel is a chiral compound widely used as an antiplatelet medication that lowers the risk of blood clots, strokes, and heart attacks. The main aim of the study presented herein was to obtain ()-clopidogrel, which is commercially available in treatments, via the kinetic resolution of racemic clopidogrel carboxylic acid with the use of lipase from and a two-phase reaction medium containing an ionic liquid. For this purpose, the enantioselective biotransformation of clopidogrel carboxylic acid and chiral chromatographic separation with the use of a UPLC-MS/MS system were optimized. The best kinetic resolution parameters were obtained by using a catalytic system containing lipase from OF as a biocatalyst, cyclohexane and [EMIM][BF4] as a two-phase reaction medium, and methanol as an acyl acceptor. The enantiomeric excess of the product was ee = 94.21% ± 1.07 and the conversion was c = 49.60% ± 0.57%, whereas the enantioselectivity was E = 113.40 ± 1.29. The performed study proved the possibility of obtaining ()-clopidogrel with the use of lipase as a biocatalyst and a two-phase reaction medium containing an ionic liquid, which is in parallel with green chemistry methodology and does not require environmentally harmful conditions.
氯吡格雷是一种手性化合物，广泛用作抗血小板药物，可降低血栓、中风和心脏病发作的风险。本研究的主要目的是通过使用 和含有离子液体的两相反应介质中的脂肪酶，从外消旋氯吡格雷羧酸获得（）-氯吡格雷，（）-氯吡格雷可在治疗中获得。为此，优化了氯吡格雷羧酸的对映选择性生物转化和使用 UPLC-MS/MS 系统的手性色谱分离。通过使用含有脂肪酶的催化体系，获得了最佳的动力学拆分参数，脂肪酶来自 OF 作为生物催化剂，环己烷和 [EMIM][BF4] 作为两相反应介质，甲醇作为酰基受体。产物的对映体过量 ee = 94.21% ± 1.07，转化率 c = 49.60% ± 0.57%，而对映选择性 E = 113.40 ± 1.29。进行的研究证明了使用脂肪酶作为生物催化剂和含有离子液体的两相反应介质获得（）-氯吡格雷的可能性，这与绿色化学方法并行，并且不需要对环境有害的条件。
