残留偶极耦合参数在有机分子结构解析及NMR波谱在手性识别中的应用

发布时间：2018-02-16 11:25

本文关键词： 核磁共振残留偶极耦合定向介质合成高分子液晶手性分析有机小分子手性溶剂化试剂　出处：《南京大学》2017年博士论文　论文类型：学位论文

【摘要】：天然和合成有机分子结构鉴定,特别是立体化学解析一直是有机化学和药物化学的核心任务之一。利用常规的化学位移(δ)、3J耦合、NOE效应等核磁共振参数存在一定的局限性。作为核磁共振各向异性参数,残留偶极耦合(residual dipolar coupling,RDC)可提供独特的结构信息,在立体结构分析中的重要作用正被逐步展示。但RDC提取与分析需要分子定向介质,而迄今仅有少数与有机溶剂相溶的弱定向介质可供选用。因此,发展和构筑新型、简便实用的,具有手性识别性能的弱定向介质用于RDC参数采集与分析,是拓展核磁共振各向异性参数在有机小分子结构分析与应用的重要课题。针对此问题,本论文开展了以下研究工作:1.对残留偶极耦合在有机小分子结构确证方面的发展进行综述,归纳总结了测定有机小分子RDC的定向介质和检测分析方法,并利用实例展示了 RDC各向异性参数在解析天然产物立体构型的独到优势。2.发展了一类新型螺旋二肽聚异腈液晶弱定向介质,它可在较低浓度的氯仿溶液中自成液晶相。这一特征被成功用于马钱子碱、雷公藤甲素等复杂天然分子的立体化学研究;RDC计算结果与其单晶原子坐标的空间构型相吻合,可清晰区分有机分子异松蒎醇的对映体异构体;表明本工作创建的螺旋二肽聚异腈液晶丰富了 RDC提取介质,从而拓展了 RDC在有机结构分析中的应用。3.设计合成了一种新型的聚苯基异腈手性高分子,并将其发展为一类手性液晶,深入研究了它在异松蒎醇对映异构体区分测定中的应用空间;同时它也可使青蒿素,石斛碱等多种类型的手性分子产生定向排列,结果显示用其测得的RDC值在合适的范围内。以上事实表明,这些新合成手性定向介质在解析复杂天然产物和有机合成分子立体化学方面具有广阔应用前景。4.作为以上工作的延生和补充,论文的第四章发展了以脯氨酸骨架衍生的一类氨基醇手性溶剂化试剂,它们通过1 H NMR可识别手性羟基羧酸类化合物的不同对映体组成,准确快速地分析手性化合物的ee值及相关立体异构体的绝对构型。这些工作为分析手性药物对映体纯度提供了新方法,拓宽了现存的手性溶剂化试剂在手性对映体组成分析中的应用。
[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.
【学位授予单位】：南京大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.13;O657.2

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