New materials and strategies for NMR based structural elucidation of organic molecules

几十年来，以核磁共振为基础的有机分子的结构解析主要是通过对化学位移、J偶联和核Overhauser效应(NOE)的评价来实现的。近年来，核磁共振各向异性参数的测量，如剩余偶极耦合(RDC)或最近的剩余化学位移各向异性(RCSA)的测量，可以准确地确定复杂和具有挑战性的分子的组成、构型和构象。该技术基于使用各向异性体系引入弱分子有序，例如溶致相或机械应变聚合物凝胶。巴西-德国团队在该领域的下列方面有长期的合作：(I)开发具有更好的机械和光谱性能并与各种溶剂兼容的新型手性对准介质材料；(Ii)开发新的脉冲序列和方法，以便更准确地提取各向异性参数；(Iii)开发新的分析和软件工具，用于使用各向异性核磁共振参数确定相对和绝对构型；(Iv)应用于要求苛刻的结构问题。提出的建议旨在加强合作，并特别致力于开发新的对准介质，以有效和准确地测量碳、质子甚至异核RCSA。此外，他们还将开发新的策略来解释高柔性分子的各向异性核磁共振数据。这些新方法将被应用于解决杂环分子、抗菌肽以及仅存在于非常有限数量的新型天然产物的结构问题。

For many decades, NMR-based structural elucidation of organic molecules was dominated by the evaluation of chemical shifts, J-couplings and nuclear Overhauser effects (NOEs). In the last years it has been proved that the measurement of anisotropic NMR parameters such as residual dipolar couplings (RDCs) or more recently residual chemical shift anisotropies (RCSAs) can lead to accurate determination of constitution, configuration and conformation of complex and challenging molecules. The technique is based on the introduction of a weak molecular order using anisotropic system, e.g. lyotropic phases or mechanically strained polymer gels. Brazilian-German teams have long-term collaborations on following aspects of this field: (i) development of new chiral aligning media materials with improved mechanical and spectroscopical properties and compatible with a variety of solvents; (ii) Development of new pulse sequences and methodologies for more accurate extraction of anisotropic parameters; (iii) Development of new analysis and software tools for the determination of relative and absolute configuration using anisotropic NMR parameter; (iv) Application to demanding structural problems. The presented proposal will aim at strengthening their collaborations and put special effort on developing new alignment media for efficient and accurate measurement of carbon, proton, and even heteronuclei RCSAs. Furthermore, they will develop new strategies for interpreting anisotropic NMR data of highly flexible molecules. These new methods will be applied to solve structural problems of heterocyclic molecules, antimicrobial peptides, as well as novel natural products that exist only in very limited amounts.