本文選題：高效液相色譜法 + 奎寧衍生物　； 參考：《鄭州大學(xué)》2014年碩士論文

【摘要】：手性是自然界的物質(zhì)屬性之一。大多數(shù)手性藥物以外消旋體的形式存在。而單一構(gòu)型的藥物由于其作用位點(diǎn)明確，見(jiàn)效快，已經(jīng)成為藥物研發(fā)的璀璨明星。因而，各種新型的手性藥物的分離與分析技術(shù)應(yīng)運(yùn)而生。其中，手性固定相法應(yīng)用最為廣泛。 球形氨丙基乙基橋連介孔硅膠（APEPMOs）中不僅含有氨丙基和乙撐基兩種官能團(tuán)，球形形貌，而且具有高度有序的介孔通道、較大的比表面積、較高的容量和機(jī)械強(qiáng)度，不僅可以直接作為常規(guī)液相色譜柱填料，并且其側(cè)鏈上的氨丙基為富電子的活性官能團(tuán)，可以為后續(xù)的衍生化修飾提供便利；其通透性較好，在快速分離分析方面有一定的優(yōu)勢(shì)。而目前為止，成功制備球形氨丙基修飾的PMOs的報(bào)道還比較少。而對(duì)于手性選擇劑奎寧而言，一直以來(lái)，人們都致力于制備奎寧、奎寧衍生物鍵合手性固定相及正相條件下拆分手性對(duì)映體的研究，但很少有文獻(xiàn)報(bào)道在反相洗脫模式下，考察流動(dòng)相變量（如流動(dòng)相組成等）對(duì)手性化合物拆分的影響。因此，手性選擇劑奎寧衍生物與雜化介孔硅膠的結(jié)合，和對(duì)其在反相條件下應(yīng)用的研究有著理論基礎(chǔ)和必要性。 本文旨在開(kāi)發(fā)一種新型手性固定相，為建立高效、快速的手性藥物拆分方法提供新型的分離材料。以APEPMOs為固定相的鍵合基質(zhì)，以QN為手性選擇劑，將QN鍵合到介孔硅膠上，制備出新型奎寧衍生物鍵合手性固定相，并將其制備成手性色譜柱，評(píng)價(jià)了自制手性柱的色譜性能及在反相洗脫模式下對(duì)多種手性藥物的拆分能力。 首先，以1,2-二（三乙氧基硅基）乙烷（BTSE）和3-氨丙基三乙氧基硅烷（KH-550）為雙硅源，以陽(yáng)離子表面活性劑十八烷基三甲基氯化銨（C18TACl）為模板，，乙醇為助溶劑，在堿性條件下通過(guò)一步共縮聚合成新型氨丙基乙基橋連球形介孔硅膠；再以偶氮二異丁腈為引發(fā)劑，與O-9-（叔丁酯氨基甲酰）奎寧（QN）反應(yīng)，合成奎寧衍生物鍵合新型雜化介孔硅膠手性固定相。并對(duì)每一步的反應(yīng)產(chǎn)物進(jìn)行相應(yīng)的純化和表征，表征方法主要有傅里葉紅外分光光度計(jì)（FT-IR）、元素分析、掃描電子顯微鏡（Scanning electron microscope, SEM）以及氮?dú)馕綄?shí)驗(yàn)，最終得到結(jié)構(gòu)明確的手性固定相。采用濕法裝柱，以三氯甲烷-二氧六環(huán)（50/50, V/V）為勻漿液，將合成的手性固定相填裝于不銹鋼液相色譜柱中，制得新型手性液相色譜柱。 其次，研究自制奎寧衍生物鍵合氨丙基介孔硅膠手性色譜柱在高效液相色譜（HPLC）中的應(yīng)用。在反相洗脫模式下，扁桃酸及其衍生物鄰氯扁桃酸、酮洛芬3種手性藥物達(dá)到了基線分離（Rs1.5），并系統(tǒng)地考察了流動(dòng)相改性劑的濃度、柱溫及流速等因素對(duì)手性藥物對(duì)映體分離的影響。 最后，本文考察了自制手性色譜柱的重復(fù)性和穩(wěn)定性，對(duì)三個(gè)不同批次的自制手性色譜柱進(jìn)行考察，得知其手性識(shí)別能力及柱效基本保持一致，從而說(shuō)明自制手性柱的重復(fù)性較好；通過(guò)對(duì)同一自制手性色譜柱在不同時(shí)間段色譜性能的考察，發(fā)現(xiàn)其手性識(shí)別能力減弱，柱效有所降低，說(shuō)明其穩(wěn)定性不太好�？赡苡捎阪I合量問(wèn)題，部分藥物對(duì)映體未能達(dá)到基線分離。
[Abstract]:Chiral is one of the material properties of nature. Most of the chiral drugs exist in the form of racemes. And single configuration drugs have become the resplendent star of drug research and development because of their clear action sites and fast effect. Therefore, the separation and analysis techniques of various new chiral drugs have emerged. For a wide range.
Spherical amino propyl ethyl bridged mesoporous silica gel (APEPMOs) not only contains two kinds of functional groups, such as propyl and ethopyl groups, spherical morphology, highly ordered mesoporous channels, larger specific surface area, higher capacity and mechanical strength, not only can be directly used as conventional liquid chromatography column filler, but also its side chain is rich in propyl. The active functional groups of the children can provide convenience for subsequent derivatization, and their permeability is good and has some advantages in rapid separation and analysis. So far, there are few reports on the successful preparation of spherical modified PMOs. The study of chiral chiral stationary phase and chiral enantiomer under normal phase is studied by Ningyan, but few reports have been reported on the effect of the separation of chiral compounds in the reverse phase elution mode, such as the composition of mobile phase, etc. There is a theoretical basis and necessity for the research under the application.
The aim of this paper is to develop a new chiral stationary phase, which provides a new separation material for the establishment of high efficient and fast chiral separation method. Using APEPMOs as the bonding matrix and QN as the chiral selector, the QN bond is bonded to the mesoporous silica gel to prepare a new type of chiral stationary phase of quinine derivatives, and the chiral chromatography is prepared. The chromatographic properties of the self-made chiral column and the resolution ability of chiral drugs in the reverse elution mode were evaluated.
First, 1,2- two (triethoxyl silicyl) ethane (BTSE) and 3- ammonia propyl triethoxy silane (KH-550) were used as two silicon sources, with cationic surfactant eighteen alkyl three methyl ammonium chloride (C18TACl) as the template and ethanol as a cosolvent, a new type of propyl ethyl bridge spherical mesoporous silica gel was synthesized by one step co polycondensation under alkaline conditions. Nitrogen two isobutyl nitrile was used as an initiator to react with O-9- (tert butyl amino formyl) quinine (QN) to synthesize quinine derivatives bonding new hybrid mesoporous silica chiral stationary phase. The reaction products of each step were purified and characterized. The main characterization methods were Fourier infrared spectrophotometer (FT-IR), element analysis, scanning electron microscope (Sc). Anning electron microscope, SEM) and nitrogen adsorption experiments were carried out. Finally, the chiral stationary phase with clear structure was obtained. The chiral stationary phase was filled in the stainless steel liquid chromatography column using the wet packed column and the trichloromethane - two oxygen six ring (50/50, V/V) as the homogenate.
Secondly, the application of the homemade quinine derivative bonded mesoporous silica chiral chromatographic column in high performance liquid chromatography (HPLC) was studied. Under the reverse phase elution mode, 3 kinds of chiral drugs, almanic acid and its derivatives, oalmanic acid and ketoprofen, reached the baseline separation (Rs1.5), and the concentration, column temperature and flow velocity of the mobile phase modifier were systematically investigated. The effect of adversary drug on enantiomer separation.
Finally, the reproducibility and stability of the homemade chiral chromatographic column were investigated, and the self-made chiral chromatographic columns of three different batches were investigated. It was found that the chiral recognition ability and the column efficiency were basically consistent, which indicated that the reproducibility of the homemade chiral column was better, and the performance of the chromatographic column of the same self made chiral chromatographic column was in different time periods. It is found that the chiral recognition ability is weakened and the column efficiency is reduced, indicating that its stability is not very good.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R943

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相關(guān)期刊論文 前3條

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本文編號(hào)：2023508