A new and robust pipeline for absolute configuration determination is presented here.
First, virtual screening selects chiral probes compatible with the active pharmaceutical ingredient (API). Second, crystallization trials produce microcrystals suitable for analysis without further optimization. Finally, MicroED is used to determine the crystal structure. The absolute configuration of the API can be confidently assigned relative to the chiral probe.
Shah, H. S., Yuan, J., Xie, T., Yang, Z., Chang, C., Greenwell, C., Zeng, Q., Sun, G., Read, B. N., Wilson, T. S., Valle, H. U., Kuang, S., Wang, J., Sekharan, S., Bruhn, J. F., Absolute Configuration Determination of Chiral API Molecules by MicroED Analysis of Cocrystal Powders Formed Based on Cocrystal Propensity Prediction Calculations, Chem. Eur. J. 2023; doi.org/10.1002/chem.202203970
