The .9 Aha Asymmetric Synthesis Of High Performance Liquid Chiral Separation,

Chirality is the intrinsic characteristic of nature.The determination of the conFig.uration of chiral compounds has triggered widespread interests due to the important role of chiral organic compounds in the academic field of chemistry,physics,biology and pharmacy.The case of Thalidomide urged scientists to study chiral organic compounds in a profound level.Many ways have been applied for the determination of the absolute stereochemistry of chiral compounds,such as X-ray crystallography,circular dichroism(CD),optical rotatory dispersion(ORD) and NMR spectroscopy.The use of NMR spectroscopy for the determination of the absolute conFig.uration of chiral compounds has some obvious merits:the easy operation of the instrument,low expenditure, small amount of sample and wide application.The chiral derivatizing reagents(CDAs) are a current method to determine the absolute stereochemistry of chiral compounds by NMR.The CDAs uses aryl methoxyacetic acids(AMAAs) and aryl hydroxyacetate esters(AHAs) to react with alcohol, amine and carboxylic acid to obtain the corresponding ester or amide respectively,then through comparison and analysis of the NMR signals of ester or amide,the absolute conFig.uration of chiral alcohol,amine and carboxylic acid can be assured.However,there are many difficulties in the preparation and resolution of AMAAs and AHAs, so this thesis focuses on the asymmetric synthesis and HPLC chiml resolutions of the widely used Chiral Derivatizing Reagents(9-anthryl)methoxyacetic acid(9AMAA),ethyl 2-hydroxy-2-(9-anthryl) acetate(9AHA) and its derivatives,and some development has been achieved.This paper includes:1.The review of the methods for determination of the absolute configuration of chiral compounds,the asymmetric reduction of aehiral ketones and the HPLC resolution of ehiral compounds.The principel and method for the determination of the absolute stereochemistry of chiral alcohols,amines and carboxylic acids using AMAAs and AHAs were introduced.The methods for obtaining optical alcohols such as:the asymmetric reduction by chiral modified LiAlH₄,chiral assisted reagent modified NaBH4,oxazaborolidine catalyst system for reduction,transition metal-complex catalyzed hydrogenation and asymmetric reduction of carbonyl compounds by catalyzing with yeast were introduced,the oxazaborolidine catalyst system for asymmetric reduction and the transition metal-complex catalyzed hydrogenation were discussed in detail.We also briefly introduced the high performance liquid chromatography(HPLC),which included the principel and different types of the detectors,the principle and the application of chiralHPLC chiral stationary phases(CSPs) in asymmetric synthesis,asymmetric catalysis and chiral drug research.2.The HPLC resolution of 9AHA,9AMAA and its derivativesIn order to determine the enantiomeric excess value of 9AHA and 9AMAA in the asymmetric synthesis,the optial purity of 9AHA and its derivatives,a resolution method based on HPLC with a chiral column has been developed and validated for the qualitative analysis.The best resolution condition for the qualitative analysis of 9AHA and 9AMA was built.The effects of concentration of the alcoholic modifier,temperature and flow rate on the separation capability,resolution and retention time were discussed.The 9AHA and its derivatives were characterized by NMR,IR spectra,UV and melting points.3.The asymmetric synthesis of 9AHA and 9AMAAThe method using the chiral derivatizing reagents(CDAs) to determine the absolute stereochemistry of chiral compounds usually needs only one enantiomer of the cacemic enantiomer. According to the law of green chemisty,we have tried the asymmetric synthesis of 9AHA in order to avoid the unnecessary resolution.The asymmetric inducement synthesis and oxazaborolidine catalyst system were performed in our experiments and the results of the two methods were compared.The single crystal of(+)-bornyl(9-anthryl) acetate obtained in the experiment was characterized.