College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Korea.
Arch Pharm Res. 2010 Sep;33(9):1301-6. doi: 10.1007/s12272-010-0902-1. Epub 2010 Oct 9.
Stereoisomers of nadolol were derivatized with S-(-)-menthyl chloroformate((-)-MCF) forming their diastereomers, RSR-nadolol-(-)-MCF, SRS-nadolol-(-)-MCF, RRS-nadolol-(-)-MCF and SSRnadolol-(-)-MCF. Diastereomeric mixture were then chromatographically resolved by preparative HPLC (JAIGEL-ODS-BP-L, 500 × 25 mm column) eluted with methanol-water (84:16, v/v) at flow rate 2.5 mL/min. RSR-nadolol-(-)-MCF diastereomer was hydrolyzed with 5% LiOH at 80°C for 48 h, and the decomposed mixture was further purified by semi-preparative HPLC. The purity and final yield of RSR-nadolol were 99.97% and 12.95%, respectively.
那多洛尔的对映异构体与 S-(-)-薄荷基氯甲酸酯((-)-MCF)衍生化形成非对映异构体，RSR-那多洛尔-(-)-MCF、SRS-那多洛尔-(-)-MCF、RRS-那多洛尔-(-)-MCF 和 SSR-那多洛尔-(-)-MCF。然后通过制备高效液相色谱法（JAIGEL-ODS-BP-L，500×25mm 柱）以甲醇-水（84:16，v/v）为洗脱剂，流速为 2.5mL/min 对非对映异构体混合物进行色谱分离。RSR-那多洛尔-(-)-MCF 非对映异构体在 80°C 下用 5%LiOH 水解 48 小时，分解混合物进一步通过半制备高效液相色谱法纯化。RSR-那多洛尔的纯度和最终收率分别为 99.97%和 12.95%。
