Absolute configuration determination of SMTP-7 via microcrystal electron diffraction (MicroED)

Direct absolute configuration determination of a drug candidate bearing five chiral centers, SMTP-7, is lacking. With only few-micron-sized powders available, we assigned the absolute configuration of SMTP-7 via MicroED analysis through kinematical refinement with additional chiral information and directly through the recently developed dynamical refinement approach. We showcased the utility of the latest advance in MicroED to unambiguously assign absolute configuration for hard-to-crystallize, complex, and quantity-limited molecules.

Automated summary

In this study, we used MicroED analysis with kinematical refinement and the recently developed dynamical refinement approach to determine the absolute configuration of a drug candidate, SMTP-7, which bears five chiral centers. This method demonstrated its utility in unambiguously assigning absolute configuration for molecules that are hard to crystallize, complex, and limited in quantity.