Tang Y, Reepmeyer J C, Revelle L K, Wilson J A
Food and Drug Administration, Division of Drug Analysis, St. Louis, MO, USA.
J Chromatogr A. 1996 Nov 1;752(1-2):93-9. doi: 10.1016/s0021-9673(96)00463-3.
This paper reports HPLC methodology for the first successful enantiomeric separations of 3-phenylacetylamino-2,6-piperidinedione (PAP), a naturally occurring peptide derivative used for inhibiting the growth of cancer tissues. The chiral separation of four related hydrolysates is also described. A commercially available tris-4-methylbenzoate cellulose (Chiralcel OJ) column was used as the chiral stationary phase, operated in the normal-phase, mode. The results demonstrated that hydrolyzed products of PAP, each of which has a carboxylic acid functionality present in its structure, eluted in a reasonable time and are enantiomerically resolved only when a trace amount of organic acid is present in the mobile phase. Different alcohols (ethanol and isopropanol) and acid additives (trifluoroacetic acid, trichloroacetic acid and acetic acid) were evaluated. In general, for the separation of the acidic enantiomers, ethanol is superior to isopropanol and stronger acids enhance the resolution more effectively. However, chiral separation of PAP could only be accomplished with isopropanol in the mobile phase and no acidic additive was needed.
本文报道了高效液相色谱法，首次成功拆分了3-苯乙酰氨基-2,6-哌啶二酮（PAP），这是一种用于抑制癌组织生长的天然肽衍生物。文中还描述了四种相关水解产物的手性拆分情况。使用市售的三（4-甲基苯甲酸）纤维素（手性cel OJ）柱作为手性固定相，采用正相模式操作。结果表明，PAP的水解产物，其结构中均含有羧酸官能团，在合理时间内洗脱，且只有当流动相中存在痕量有机酸时才能实现对映体拆分。评估了不同的醇类（乙醇和异丙醇）和酸添加剂（三氟乙酸、三氯乙酸和乙酸）。一般来说，对于酸性对映体的拆分，乙醇优于异丙醇，且更强的酸能更有效地提高拆分度。然而，PAP的手性拆分只能在流动相中使用异丙醇且无需酸性添加剂的情况下完成。
