5-乙氧基羰基特特拉姆酸甲酯和5-乙氧基羰基-4-羟基-2-吡咯烷酮对映体液相色谱拆分研究

HPLC Enantioseparation of Methyl 5-Ethyloxylcarbonyltetramate and 5-Ethyloxylcarbonyl-4-hydroxy-2-pyrrolidinone

合成了外消旋5-乙氧基羰基特特拉姆酸甲酯(1)和顺/反式5-乙氧基羰基-4-羟基-2-吡咯烷酮(2),并利用手性高效液相色谱制备少量的单一对映体标样进行圆二色光谱表征。在此基础上,系统研究了这3对外消旋体化合物在Chiralpak AD-H和Chiralcel OD-H手性柱上的液相色谱拆分行为和对映体出峰顺序。采用正己烷-异丙醇(体积比60∶40)作流动相,外消旋化合物1在Chiralpak AD-H柱上得到很好的拆分,k1、α和RS分别为0.99、2.65和12.5;采用正己烷-异丙醇(体积比80∶20)作流动相,化合物2的4个立体异构体可以同时在Chiralpak AD-H柱上得到基线分离,反式-2对映体的k1、α1和RS1分别为1.69、1.12和1.56,顺式-2对映体的k、α和R分别为2.58、1.16和2.28。

Racemic methyl 5-ethyloxylcarbonyltetramate （ 1 ） and trans/cis-5-ethyloxylcarbonyl-4-hy- droxy-2-pyrrolidinone（2） were synthesized. The single enantiomer of compound 1 and 2 was prepared by chiral HPLC and characterized by CD. The chromatographic behaviors and enantiomer elution order of these compounds were investigated on the Chiralpak AD-H and Chiralcel OD-H columns in normal phase mode. A good resolution of racemic compound 1 was obtained on the Chiralpak AD- H column with n-hexane/2-propanol（60 ： 40, by volume）as mobile phase, the values of α and Rs were 2.65 and 12.5 respectively. A baseline separation of four stereoisomers of the racemate 2 was also obtained on the Chiralpak AD-H column with n-hexane/2-propanol（80 ： 20, by volume）as mobile phase. The values of α1 and α2 were 1.12 and 1.16 respectively for trans-2 and cis-2.