發(fā)布時(shí)間：2018-02-16 11:25

  本文關(guān)鍵詞： 核磁共振殘留偶極耦合 定向介質(zhì) 合成高分子液晶 手性分析 有機(jī)小分子 手性溶劑化試劑　出處：《南京大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：天然和合成有機(jī)分子結(jié)構(gòu)鑒定,特別是立體化學(xué)解析一直是有機(jī)化學(xué)和藥物化學(xué)的核心任務(wù)之一。利用常規(guī)的化學(xué)位移(δ)、3J耦合、NOE效應(yīng)等核磁共振參數(shù)存在一定的局限性。作為核磁共振各向異性參數(shù),殘留偶極耦合(residual dipolar coupling,RDC)可提供獨(dú)特的結(jié)構(gòu)信息,在立體結(jié)構(gòu)分析中的重要作用正被逐步展示。但RDC提取與分析需要分子定向介質(zhì),而迄今僅有少數(shù)與有機(jī)溶劑相溶的弱定向介質(zhì)可供選用。因此,發(fā)展和構(gòu)筑新型、簡便實(shí)用的,具有手性識別性能的弱定向介質(zhì)用于RDC參數(shù)采集與分析,是拓展核磁共振各向異性參數(shù)在有機(jī)小分子結(jié)構(gòu)分析與應(yīng)用的重要課題。針對此問題,本論文開展了以下研究工作:1.對殘留偶極耦合在有機(jī)小分子結(jié)構(gòu)確證方面的發(fā)展進(jìn)行綜述,歸納總結(jié)了測定有機(jī)小分子RDC的定向介質(zhì)和檢測分析方法,并利用實(shí)例展示了 RDC各向異性參數(shù)在解析天然產(chǎn)物立體構(gòu)型的獨(dú)到優(yōu)勢。2.發(fā)展了一類新型螺旋二肽聚異腈液晶弱定向介質(zhì),它可在較低濃度的氯仿溶液中自成液晶相。這一特征被成功用于馬錢子堿、雷公藤甲素等復(fù)雜天然分子的立體化學(xué)研究;RDC計(jì)算結(jié)果與其單晶原子坐標(biāo)的空間構(gòu)型相吻合,可清晰區(qū)分有機(jī)分子異松蒎醇的對映體異構(gòu)體;表明本工作創(chuàng)建的螺旋二肽聚異腈液晶豐富了 RDC提取介質(zhì),從而拓展了 RDC在有機(jī)結(jié)構(gòu)分析中的應(yīng)用。3.設(shè)計(jì)合成了一種新型的聚苯基異腈手性高分子,并將其發(fā)展為一類手性液晶,深入研究了它在異松蒎醇對映異構(gòu)體區(qū)分測定中的應(yīng)用空間;同時(shí)它也可使青蒿素,石斛堿等多種類型的手性分子產(chǎn)生定向排列,結(jié)果顯示用其測得的RDC值在合適的范圍內(nèi)。以上事實(shí)表明,這些新合成手性定向介質(zhì)在解析復(fù)雜天然產(chǎn)物和有機(jī)合成分子立體化學(xué)方面具有廣闊應(yīng)用前景。4.作為以上工作的延生和補(bǔ)充,論文的第四章發(fā)展了以脯氨酸骨架衍生的一類氨基醇手性溶劑化試劑,它們通過1 H NMR可識別手性羥基羧酸類化合物的不同對映體組成,準(zhǔn)確快速地分析手性化合物的ee值及相關(guān)立體異構(gòu)體的絕對構(gòu)型。這些工作為分析手性藥物對映體純度提供了新方法,拓寬了現(xiàn)存的手性溶劑化試劑在手性對映體組成分析中的應(yīng)用。
[Abstract]:Structural identification of natural and synthetic organic molecules, In particular, stereochemical resolution has always been the core of organic chemistry and pharmaceutical chemistry. There are some limitations in the use of conventional chemical shift (未 ~ + ~ (3J)) coupled with Noe effect and other nuclear magnetic resonance parameters, which are considered as anisotropic parameters of nuclear magnetic resonance (NMR). Residual dipolar coupling can provide unique structural information, and its important role in stereoscopic structure analysis is being gradually demonstrated. However, RDC extraction and analysis require molecular oriented media. So far, only a few weak directional media dissolving with organic solvents are available. Therefore, a new, simple and practical weak directional medium with chiral recognition property is developed and constructed for RDC parameter acquisition and analysis. It is an important subject to extend the anisotropic parameters of NMR in the analysis and application of organic small molecular structure. In this paper, the following research work was carried out: 1. The development of residual dipole coupling in the identification of the structure of organic small molecules was reviewed, and the directional medium and analytical methods for the determination of RDC were summarized. The unique advantage of anisotropic parameters of RDC in the analysis of the three-dimensional configuration of natural products is demonstrated by an example. 2. A new kind of weak directional medium of helical dipeptide polyisonitrile liquid crystal is developed. It can form its own liquid crystal phase in low concentration chloroform solution. This characteristic has been successfully used to study the stereochemistry of complex natural molecules such as brucine, triptolide and so on. The results of RDC calculation are in agreement with the spatial configuration of its single crystal atomic coordinates. The enantiomer isomers of the organic molecule isopentanol can be clearly distinguished, which indicates that the helical dipeptide polyisonitrile liquid crystal created in this work enriches the extraction medium of RDC. Therefore, the application of RDC in organic structure analysis was expanded. 3. A novel poly (phenylisonitrile) chiral polymer was designed and synthesized, and developed into a chiral liquid crystal. The application space of isoppinol enantiomers in the determination of isoponitol enantiomers was studied in depth, and the chiral molecules such as artemisinin, Dendrobium alkaloids and other chiral molecules were orientated. The results show that the RDC values measured are in the appropriate range. These new synthetic chiral oriented media have broad application prospects in the analysis of complex natural products and organic synthesis molecular stereochemistry. In Chapter 4th, a class of amino alcohol chiral solvation reagents derived from proline skeleton are developed. They can recognize different enantiomers of chiral hydroxy carboxylic acids by 1H NMR. The ee value of chiral compounds and the absolute configuration of the related stereoisomers are analyzed accurately and rapidly. These work provide a new method for the analysis of enantiomeric purity of chiral drugs. The application of the existing chiral solvation reagents in the analysis of enantiomeric composition of chiral compounds has been broadened.
【學(xué)位授予單位】：南京大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：O621.13;O657.2

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