小分子的共结晶绝对构型。

Institute of Organic Chemistry, University of Stuttgart, 70569, Stuttgart, Germany.

Angew Chem Int Ed Engl. 2020 Sep 7;59(37):15875-15879. doi: 10.1002/anie.202004992. Epub 2020 Jun 29.

The most reliable method to determine the absolute configuration of chiral molecules is X-ray crystallography, but small molecules can be difficult to crystallize. We report rapid co-crystallization of tetraaryladamantanes with small molecules as different as n-decane to nicotine to produce crystals for X-ray analysis and the assignment of absolute configuration when the molecules are chiral. A screen of 52 diverse compounds gave inclusion in co-crystals for 88 % of all cases and a high-resolution structure in 77 % of cases. Furthermore, starting from three milligrams of analyte, a combination of NMR spectroscopy and X-ray crystallography produced a full structure in less than three days using an adamantane crystallization chaperone that encapsulates the analyte at room temperature.

确定手性分子绝对构型最可靠的方法是 X 射线晶体学，但小分子很难结晶。我们报告了四芳基金刚烷与小分子（如正癸烷、尼古丁）的快速共结晶，生成可用于 X 射线分析的晶体，并在手性分子的情况下确定其绝对构型。对 52 种不同化合物进行筛选，共晶包含率为 88%，高分辨率结构为 77%。此外，从 3 毫克分析物开始，使用金刚烷结晶助溶剂，通过 NMR 光谱和 X 射线晶体学的组合，在不到三天的时间内即可获得完整结构，该助溶剂在室温下将分析物包裹在内。