Synthesis And Resolution Of 2-(9-Anthryl)-2-Hydroxyacetic Acid

Chirality is a universal phenomenon in the nature, especially in Pharmaceuticals, biological molecules and agrochemicals. Whereas the tridimensional structure of organic molecule has special relation with its biological activity, it is significant to establish enantiomers separating and measuring method of high specialization and high degree of resolution for boosting molecular activity and lessening side-effect and researching mechanism of action in depth. Nowadays, the manufacture and production of optically pure drugs is the trend of new drugs research. The study on chiral drugs has become one of the new directions of new drugs research internationally. Analysis of chiral drugs, with increasing importance in chiral pharmaceutical research, has become a hot and difficult topic in international analysis science. The study of pharmacology and toxicologically speciality of chiral drugs and compounds is more and more highly valued, along with various understanding of biological activity caused by tridimensional structure of chiral compounds. One of the pivotal and basal techniques in researching of chiral compounds is the separation analysis of chiral compounds. In the early 1980s, the routine and rapid analytical means of chiral compounds didn't appear. However, by the early 1990s, fast advancement in the field of separation technology was made. Many scientists focus on chromatography gradually in virtue of its strong applicability, wide application prospects and high degree of resolution purity.Optically pure 2-(9-anthryl)-2-hydroxyacetic acid (9AHAA) is the pre-compound of chiral auxiliary reagents ethyl-2-(9-anthryl)-2-hydroxyacetate (9AHA) and 2-(9-anthryl)-2-methoxyacetic acid (9AMAA). 9AHA and 9AMAA have their original effects on mensurating the absolute configuration of chiral carbon atom. We researched the regular chiral resolution methods of enantiomer 9AHA from its synthesis, which would make preparations for the other important work in our laboratory later. This paper mainly concludes the following contents:The first chapter briefly summarized the study of chiral compounds. There are many contents with regard to correlative knowledge of chiral compounds. We mostly expatiate on the following five facets: the foundational knowledge of chiral compounds,the significance of chiral resolution, the research status quo and new development of chiral medicament, the resolution methods of chiral compounds and chiral stationary phase of chromatography. People have realized the difference of physiological function and metabolization process of optical chiral compounds in organism with the development of life science, especially life chemistry and medicine chemistry. Chirality revolution has emerged in many fields, we could dope that chiral medicine making of optically pure molecule will become the mainstream in the world medicament market.The second chapter discussed the synthesis of 9AHAA. Based on Riguera's idea, 9AHAA could be obtained from Friedel-Crafts acylation, reduction, hydrolysis. Favorable progress was made in our experiments. We found the optimum method to synthesize target product by optimizing the conditions of reaction, and we have obtained 9AHAA with high yield. According to the fluorescence characteristic of intermediates, every experiment was monitored by TLC so that we could mensurated the end-point of reaction. Every intermediate structure was characterized by *H NMR or 13C NMR. As a result, we made success in our experiments.The third chapter investigated the synthesis and structure characterization of chiral stationary phase (CSP) cellulose tribenzoate (CTB). First of all, this part briefly summarized the synthetical methods of CTB. Then, the synthetical methods of CTB by ultrasonic means were presented in this paper. At last, the structure of CTB was characterized from various methods, mainly by the following five aspects: elemental analysis, ESEM, powder X-ray diffraction, TGA, IR. As a result, microcrystalline cellulose(MC) has been derivatized to CTB, but not totally derivatized.The fourth chapter discussed the chiral resolution of enantiomer 9AHAA.We mostly studied on the following aspects: CE separation, chemical resolution and TLC separation. The mechanism of chiral separation was primarily investigated. The result of CE separation indicated that 9AHAA was separated on baseline, when we selected HP-B-CD (DS 6.2) of 15mmol/L as chiral selector, Tris-H3PO4(pH 6.50) of 20mmol/L as buffer system, and the Rs is 1.35. The result of chemical resolution showed that two different stereoisomers of 9AHAA were obtained successfully, when we used (-)-ephedrine as resolution reagent. The result of TLC separation indicated that 9AHAA was separated well when we chose 6-CD/silica gel and CTB as chiral stationary phase at proper mobile phase system. The relative Rf is 16.69 and 36.01 respectively, which commendably illuminated the effect of chiral separation.This paper made some progress in comparison with previous study: firstly, we introduced assistance catalyzer l-methyl-2-pyrrolidinone to solid-phase reaction of Friedel-Crafts acylation, which enhanced the yield to 92.5%;secondly, to obtain optical purity of 9AHAA, (-)-ephedrine was used as resolution reagent in this experiment;lastly, we adopted TLC with CTB stationary phase to separate 9AHAA, which acquired ideal result. The experiment methods in this paper embodied some innovation and necessity, the research and exploration we made in this aspect is important, as well as significant.