Analytical and semi-preparative HPLC enantioseparation of novel pyridazin-3(2H)-one derivatives with alpha-aminophosphonate moiety using immobilized polysaccharide chiral stationary phases

作者：Zhang, Yuping; Zhang, Xiaoyan; Zhou, Jun; Song, Baoan^*; Bhadury, Pinaki S.; Hu, Deyu; Yang, Song

来源：Journal of Separation Science, 2011, 34(4): 402-408.

DOI：10.1002/jssc.201000705

• alpha-Aminophosphonate
• Absolute configuration
• Chiralpak IA column
• Enantioseparation
• Pyridazin derivatives

The direct HPLC enantioseparation of a novel series of chiral pyridazin-3(2H)-one derivatives with alpha-aminophosphonate moiety was performed on two immobilized polysaccharide chiral stationary phases (Chiralpak IA, Chiralpak IC) using n-hexane (n-Hex)/dichloromethane (DCM) mobile phase with 5% alcohol additive. Good baseline separation of the enantiomers was achieved using amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phases (Chiralpak IA) on analytical scale. The analytical method was further scaled up to semi-preparative loading to obtain small amounts of both the enantiomers of pyridazin-3(2H)-one derivative. The semi-preparative resolution of all compounds was successfully achieved with n-hexane/dichloromethane/ethanol (EtOH) as mobile phase using a semi-preparative Chiralpak IA column. The first fractions were isolated with purities of > 99.9% (enantiomeric excess (e.e.), and the second fractions were obtained with purities of > 98.2% (enantiomeric excess). The assignment of the absolute configuration was established for the F1 fraction of compound a-2 by single-crystal X-ray diffraction method.

• 出版日期2011-2
• 单位贵州大学