柱前衍生高效液相色谱法分离分析1-氮杂双环[2,2,2]辛-3-基胺对映异构体

Enantiomeric Resolution and Quantitative Determination of (R/S) 1-Azabicyclo[2,2,2]octan-3-amine by Pre-column Derivatization High Performance Liquid Chromatography

1-氮杂双环[2,2,2]辛-3-基胺是制备5-羟色胺拮抗剂药物盐酸帕洛诺司琼等的重要中间体,手性帕洛诺司琼可以通过中间体的手性分离来制备。用柱前衍生化-反相高效液相色谱法对1-氮杂双环[2,2,2]辛-3-基胺对映体进行分离并建立了检测方法。结果表明,用2,3,4,6-四-O-乙酰基-β-D-葡萄糖异硫氰酸酯(GITC)为柱前手性衍生化试剂,C18柱(300mm×4.6mm,5μm)为色谱柱,可将1-氮杂双环[2,2,2]辛-3-基胺对映体分离,其它色谱条件:流动相组成为[甲醇-乙腈-0.01mol/L四丁基溴化铵(20∶10∶75,V/V)]-(三乙胺)0·1%-(冰醋酸)0.15%,流速0.7mL/min,检测波长为266nm。在选择的测定条件下,衍生后的两非对映异构体分离度达4以上。

1-Azabicyclo [ 2, 2, 2 ] octan-3-amine is an important intermediate for the preparation of 5-Hydroxytryptamine 3-antagonist palonosetron hydrochloride. Chiral palonosetron can be synthesized by the enantioseparation of intermediates. A high performance liquid chromatographic method for the separation of 1-azabicyclo [2,2,2 ] octan-3-amine has been developed The resuhs show that the enantiomers can be separa- ted with 2,3,4,6-tetra-o-acetyl-β-D-glucopyranosyl isothiocyanate（ GITC ） as the derivatization reagent and a column of C18 （300 mm ×4.6 mm, 5 μm）. Other chromatographic conditions are mobile phase consisting of [ methanol-acetonitfile-0.01 mol/L tetrabutylamine bromine （ 20： 10： 75, V/V ] -triethanolamine 0.1% -acetic acid 0.15% at a flow rate of 0.7 mL/min and the detection wavelength at 266 nm. Under the optimum conditions two diastereoisomers were well separated （ R = 4. 165 ）.