Structural Elucidation and Absolute Stereochemistry\nfor Pharma Compounds Using MicroED

Microcrystal electron\ndiffraction (microED) is an emerging technique\nfor rapid crystallographic analysis of small molecule micro- and nanocrystals.\nIn this report, we evaluate the applicability of microED to pharmaceutical\ncompounds through the analysis of 30 samples obtained from the process\nand medicinal chemistry groups at Amgen Inc. Using only 40 h of microscope\ntime, 15 of 30 crystal structures were elucidated. From these crystal\nstructures, all chiral compounds had the correct absolute stereochemistry\nassigned by dynamical refinement of continuous rotation electron diffraction\ndata, confirming dynamical refinement as a promising tool for the\nabsolute stereochemistry determination of pharmaceutically relevant\ncompounds.