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  本文關(guān)鍵詞：PS基手性固定相的制備及其手性拆分的初步應(yīng)用　出處：《鄭州大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 氨基酸消旋 氯甲基化交聯(lián)聚苯乙烯微球 手性固定相

【摘要】：目前,光學(xué)純手性藥物的需求日漸增加,人們對手性藥物的有效拆分與制備越來越重視。高效液相色譜法(HPLC)中的手性固定相法(CSP)由于具有效率高、靈敏度高和再現(xiàn)性好等優(yōu)勢被廣泛用于手性藥物的拆分與分離,再加上其較高的柱容量,所以具有良好的工業(yè)化應(yīng)用前景。雖然已經(jīng)商業(yè)化的手性固定相有很多,但由于手性藥物的種類繁多,所需相應(yīng)的手性固定相的類型也非常多。因此,制備高效且多樣化的手性固定相是當(dāng)前手性藥物拆分領(lǐng)域的重要發(fā)展方向。本課題以L-亮氨酸(L-Leu)為手性源,將L-Leu負(fù)載到十微米級的氯甲基化聚苯乙烯微球上,制備了新型的手性固定相,并以DL-苯丙氨酸(DL-Phe)為拆分對象,對所制備的新型手性固定相的手性拆分能力做了初步的應(yīng)用研究。主要工作如下:(1)負(fù)載手性源的確定:使用模板化合物氯化芐來代替氯甲基化聚苯乙烯微球負(fù)載不同的L-氨基酸,探究其消旋化程度。研究表明,L-亮氨酸與氯化芐的反應(yīng)產(chǎn)物在強(qiáng)堿環(huán)境下沒有發(fā)生明顯的消旋化;而L-色氨酸(L-Trp)和L-脯氨酸(L-Pro)與氯化芐的反應(yīng)產(chǎn)物則發(fā)生了明顯的消旋化作用。說明L-Leu相比于其它兩種L-氨基酸更適合作為手性固定相的手性源。(2)手性固定相的制備:先使用介于分散聚合和懸浮聚合之間的聚合方法,采用苯乙烯(St)和氯甲基化苯乙烯(CMS)為共聚單體,在無水乙醇和水的混合反應(yīng)介質(zhì)中,制備了粒徑在10~100μm之間的氯甲基化交聯(lián)聚苯乙烯微球(該氯球的氯含量約為5.91%)。再以該種氯球?yàn)榛w,以L-Leu為手性源,通過相轉(zhuǎn)移催化法,成功地將L-Leu負(fù)載到氯球上制備出了聚苯乙烯基手性固定相,該條件下的親核取代反應(yīng)程度約為62.8%。(3)手性拆分的初步應(yīng)用:利用液相色譜法拆分DL-苯丙氨酸(DL-Phe),初步探究了聚苯乙烯基手性固定相的手性拆分能力。分別考察了流動相的組成和流速對DL-Phe拆分結(jié)果的影響。結(jié)果顯示,當(dāng)流動相是水或者石油醚時(shí),DL-Phe沒有被拆分;當(dāng)流動相是無水甲醇時(shí),固定相對DL-Phe有拆分作用,但是很不明顯;當(dāng)流動相是無水甲醇/石油醚時(shí),對DL-Phe的拆分效果比較好。接著考察了流動相中無水甲醇與石油醚的比例對拆分結(jié)果的影響,結(jié)果顯示,當(dāng)無水甲醇與石油醚體積比為7/3時(shí),拆分效果更優(yōu)。設(shè)定流動相的流速分別為1.0~3.0 mL/min,考察了流動相的流速對拆分結(jié)果的影響,結(jié)果顯示,隨著流動相流速的升高,其拆分程度隨之降低。
[Abstract]:At present, the demand for optical pure chiral drugs is increasing. More and more attention has been paid to the effective resolution and preparation of chiral drugs. The chiral stationary phase method (CSP) in HPLC is highly efficient. The advantages of high sensitivity and good reproducibility are widely used in the resolution and separation of chiral drugs, plus their high column capacity. Although there are many chiral stationary phases which have been commercialized, there are many kinds of chiral stationary phases which need a lot of corresponding chiral stationary phases because of the variety of chiral drugs. The preparation of high efficient and diversified chiral stationary phase is an important development direction in the field of chiral drug resolution. In this paper, L-Leu (L-Leu) is used as chiral source. A novel chiral stationary phase was prepared by loading L-Leu onto chloromethylated polystyrene microspheres of ten micron size and DL-Phe-phenylalanine was used as the resolution object. The chiral resolution ability of the novel chiral stationary phase was studied in this paper. The main work is as follows: 1). Determination of the chiral source: the template compound benzyl chloride was used instead of chloromethylated polystyrene microspheres to load different L-amino acids. The results showed that the reaction products of L-leucine and benzyl chloride had no significant racemization in strong alkali environment. L- tryptophan L-Trp) and L-proline). The products of the reaction with benzyl chloride had a significant racemization, indicating that L-Leu was more suitable as a chiral source for chiral stationary phase than the other two L- amino acids. Preparation of chiral stationary phase: first, the polymerization method between dispersion polymerization and suspension polymerization was used. Styrene (St) and chloromethylated styrene (CMSs) were used as comonomers in the mixed reaction medium of anhydrous ethanol and water. Chloromethylated crosslinked polystyrene microspheres with a diameter of 10 渭 m or 100 渭 m were prepared. The chlorine content of the microspheres was about 5.91%. The chlorine spheres were used as matrix and L-Leu as chiral source. Poly (styrene-based) chiral stationary phase was successfully prepared by phase transfer catalysis (PTC) by loading L-Leu onto chlorine spheres. The initial application of chiral resolution of DL- phenylalanine (DL-PHE) by liquid chromatography was studied. The degree of nucleophilic substitution reaction was about 62.8%. The effects of the composition and flow rate of the mobile phase on the resolution results of DL-Phe were investigated. The results showed that the mobile phase was water or petroleum ether. DL-Phe was not split; When the mobile phase is anhydrous methanol, the fixed DL-Phe can be separated, but it is not obvious. When the mobile phase is anhydrous methanol / petroleum ether, the resolution effect of DL-Phe is better. Then, the effect of the ratio of anhydrous methanol to petroleum ether on the resolution result is investigated. When the volume ratio of anhydrous methanol to petroleum ether is 7/3, the resolution effect is better. The flow rate of mobile phase is 1.0 ~ 3.0 mL / min, respectively. The effect of mobile phase flow rate on the resolution result is investigated. The results showed that the resolution degree decreased with the increase of mobile phase flow rate.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TQ460.1

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本文編號：1438623