Enantioanalysis Of Some Chiral Compounds In Asymmetric Synthesis Of Tetramate-related Natural Products By High Performance Liquid Chromatography

Chirality widely exists in our world. Chiral compounds (single enantiomers) have comprehensive applications in many fields dealing with pharmaceuticals, natural products, agrochemicals, and ferroelectric liquid crystals etc. Asymmetric synthesis is the most effective and straightly method for obtaining the single enantiomer. The enantiomeric purity which is used to estimate the value of the asymmetric synthesis is an important parameter. So determination of enantiomeric purity is a pivotal step in asymmetric synthesis.Chiral chromatography is recognized as one of the most accurate and credible methods to determine enantiomeric purity. Chiral high performance liquid chromatography (HPLC) is very convenient, highly stereoselective and flexibility. So the thesis is aimed at studying the applications of high performance liquid chromatography for enantioseparation and determination of enantiomeric purity in the asymmetric synthesis. In this thesis, enantioanalysis of several important chiral compounds in the asymmetric synthesis of 5-alkyl tetramate-related natural products were studied. The determination of the enantiomeric purity of 1-trimethylsilyl-1-decyn-3-ol by precolumn UV-derivatization chiral high performance liquid chromatography was also studied in the thesis.There are four parts in the dissertation:The first part briefly summarized the research progresses in the enantioseparation of chiral compounds, derivatization in chiral high performance liquid chromatography and the determination methods of enantiomeric purity. The chiral high performance liquid chromatography was emphasized. At last, the content of the study was briefly shown.The second part expatiated on the applications of chiral HPLC for determination of the enantiomeric purity of l-trimethylsilyl-l-decyn-3-ol in detail. The 1-decyn-3-ol enantiomers were derivatized with benzoyl chloride by esterification to the benzoates, which could be detected sensitively by an UV monitor. The racemic 3-benzoyloxy -1-trimethylsilyl-1-decyne was completely resolved on Chiralcel OD-H column. The effects of different alcohol modifiers, ethanol concentration, and column temperature and flow rate on enantioseparation of the benzoate derivatives were discussed. It was found that: The condition of the derivatization is moderation, sample pretreatment is relatively simple, the retention time is short and the analytical method is more sensitive. So the proposed method will be used for analysis of other chial alcohols and amines with poor absorption in ultraviolet region.The third part studied on racemic methyl N-protected 5-ethyloxylcarbonyl-tetramate and 5-ethyloxylcarbonyl-4-hydroxy-2-pyrrolidinone which were the intermediate chiral compounds in asymmetric synthesis of 5-alkyl tetramates. Their chromatographic behaviors of enantioseparation were investigated on the Chiralpak AD-H and Chiralcel OD-H columns in normal phase mode. In addition, a single enanisomer of them was prepared by chiral HPLC and characterized by CD spectrum. The enantiomer elution order and chiral recognition mechanism also discussed. It was found that: A good resolution of racemic N-protected 5-ethyloxylcarbonyl-tetramate was obtained on the Chiralpak AD-H column with n-hexane/i-propanol (or n-hexane/ethanol) as mobile phase; the enantiomer elution order is identical at different chromatographic conditions. A baseline separation of four stereo-isomers of the racemate 5-ethyloxylcarbonyl-4-hydroxy-2-pyrrolidinone was also obtained on the Chiralpak AD-H column with n-hexane/z-propanol as mobile phase, the enantiomer elution order is changed at different chromatographic conditions.The fourth part studied on enantioseparation and determination of the enantiomeric purity of chiral compounds in the asymmetric synthesis of natural products Belamide A and Palau'imide. It was found that: The optimal baseline separations of six pairs of newly synthesized chiral compounds were achieved with Chiralcel OD-H or Chiralpak AD-H using n-hexane/i-propanol (or n-hexane/ethanol) as mobile phase in various concentrations. The enantiomeric purities of the chiral compounds are all up to the required level, and racemization has not been obviously observed.