Mycroft Coral, Dal Poggetto Guilherme, Barbosa Thaís M, Tormena Cláudio F, Nilsson Mathias, Morris Gareth A, Castañar Laura
Department of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom.
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, OX1 3TA, United Kingdom.
J Am Chem Soc. 2023 Sep 13;145(36):19824-19831. doi: 10.1021/jacs.3c05515. Epub 2023 Aug 31.
The NMR analysis of fluorine-containing molecules, increasingly widespread due to their importance in pharmaceuticals and biochemistry, poses significant challenges. Severe peak overlap in the proton spectrum often hinders the extraction of critical structural information in the form of heteronuclear scalar coupling constants, which are crucial for determining pharmaceutical properties and biological activity. Here, a new method, IPAP-FESTA, is reported that drastically simplifies measurements of the signs and magnitudes of proton-fluorine couplings. Its usefulness is demonstrated for the structural study of the steroidal drug fluticasone propionate extracted from a commercial formulation and for assessing solvent effects on the conformational equilibrium in a physically inseparable fluorohydrin mixture.
由于含氟分子在药物和生物化学领域的重要性，其核磁共振（NMR）分析越来越普遍，但这也带来了重大挑战。质子谱中严重的峰重叠常常阻碍以异核标量耦合常数形式提取关键结构信息，而异核标量耦合常数对于确定药物性质和生物活性至关重要。在此，报道了一种新方法IPAP - FESTA，它极大地简化了质子 - 氟耦合的符号和大小的测量。该方法对于从商业制剂中提取的甾体药物丙酸氟替卡松的结构研究以及评估溶剂对物理上不可分离的氟醇混合物构象平衡的影响的实用性得到了证明。
