Synthesis And Chiral Separation Of Chiral Spiro-compounds

Chiral is one of the most important attribute in nature. The role of chiral compounds in pharmaceutical chemical,pesticide, food, increasingly prominent. As the enantiomers of chiral compounds, biological activity, toxicity, metabolism, and pharmaceutical quality of the completely different, Therefore, preparation of various chiral compounds, synthesis, performance, and racemic chiral body of international research has become a hot spot. In recent years, The use of gas chromatography, liquid chromatography, thin layer chromatography, supercritical fluid chromatography and capillary electrophoresis separation of drug enantiomers has become an important part in new drug research and analysis.In this dissertation, a series of chiral spiro compounds were prepared by pentaerythritol and contrapuntal substituted benzaldehyde, in which compounds were separated by HPLC, SFC,CE. The effect of mobile phase modifiers on a compound's retention factor(K') and resolutions (Rs) were investigated, and chromatographic conditions were optimized. It was as follow:1.3,9-di(4-R-phenyl)-2,4,8,10-tetraoxa-spiro[5.5]-undecane and other spiro compounds were prepared by pentaerythritol and counterpoint substituted benzaldehyde, and the effects of different conditions like temperature,catalyst,solvents,time and molar ratio were studied.2.3,9-di(4-formylphenyl)-2,4,8,10-tetraoxaspiro[5.5]undecane was prepared by two methods of pentaerythritol and 4-(2,2-dicyano)vinylbenzaidehyde or Phthalaldehyde Glycol monoAcetal, and these two methods were analyzed and compared.3.Three compounds were separated by HPLC, and 3,9-di-(4-methyl-phenyl)-2,4,8,10- tetraoxa-spiro[5.5]-undecane, 3,9-di-(4-formyl-phenyl)-2,4,8,10-tetraoxa-spiro[5.5]-undecane were successfully separated with the hexane and iso-propanol as mobile phase.4.Three compounds were separated by SFC, and 3,9-di-(4-cyanophenyl)-2,4,8,10- tetraoxa-spiro[5.5]-undecane,3,9-di(4-fluorophenyl)-2,4,8,10-tetraoxaspiro[5.5]undecane,3,9-di(4-hydroxylphenyl)-2,4,8,10-tetraoxaspiro[5.5]undecane were successfully separated with the iso-propanol and CO2 as mobile phase. Its reached the remarkably baseline separation.5.3,9-di(4-carboxylphenyl)-2,4,8,10-tetraoxaspiro[5.5]undecane was separated by CE, with CM-β-CD as Chiral Reagents .It reached the remarkably baseline separation.