3-甲基-γ-辛内酯的超临界流体色谱立体异构性制备拆分

Preparative resolution of stereoisomers of 3-methyl-γ-octalactone by packed column supercritical fluid chromatography

摘要:

用填充柱超临界流体色谱制备性拆分香料3-甲基-γ-辛内酯四个光学立体异构体。3-甲基-γ-辛内酯(合成的)首先在硅胶柱上制备拆分得其cis-、trans-异构体。然后，在分析模式下,考察手性柱种类、改性剂种类、改性剂含量、柱温、柱压的影响，获得拆分cis-、trans-异构体的较佳超临界流体色谱条件，cis-异构体：手性柱Chiralpak AD-H，柱温30 ℃，柱压9 MPa，改性剂甲醇含量4.0 % (v/v)，流动相流速1.5 ml/min，分离度1.45；trans-异构体：手性柱Chiralpak AD-H，柱温30 ℃，柱压10 MPa，改性剂甲醇含量4.5 % (v/v)，分离度2.24。在较佳的条件下对cis-、trans-异构体进行制备规模手性拆分得mg级四个光学立体异构体产品，光学纯度(对映体过量, e.e %)均为100%。

Abstract:

Packed column supercritical fluid chromatography (pSFC) was used to resolve preparatively the four optical stereoisomers of the flavor substance of 3-methyl-γ-octalactone. First, cis-, and trans- isomers were prepared by pSFC resolution of the synthetic molecule of 3-methyl-γ-octalactone on a silica gel column. Then, the effects of kind of chiral column, type of modifier solvent and content of modifier solvent in mobile phase, column temperature, column pressure, and flow rate on the resolution of the cis-, and trans- isomers were investigated in an analytical scale. The optimum resolution conditions for cis-isomers found were chiralpak AD-H, column temperature 30 ℃, column pressure 9 MPa, 4.0 % (v/v) methanol in mobile phase, and flow rate of mobile phase 1.5 ml/min, in which the resolution factor (Rs) achieved was 1.45; while those for trans-isomers found were chiralpak AD-H, column temperature 30 ℃,column pressure 10 MPa, 4.5% (v/v) methanol in mobile phase, and flow rate of mobile phase 1.5 ml/min, in which the resolution factor (Rs) achieved was 2.24. Following the optimum chromatographic conditions, preparative resolution of cis-, and trans- isomers of 3-methyl-γ-octalactone were performed further by pSFC, and four stereoisomers of several milligrams were obtained all in an optical purity of 100 % e. e.