Atropisomers are axially chiral molecules resulting from restricted rotation around a single bond, typically between two sp²-hybridized atoms. Once overlooked in drug discovery, they are now gaining attention due to the potential for one isomer to exhibit significantly greater biological activity than its counterpart. Isolating the active isomer can enhance drug efficacy and specificity while minimizing off-target effects. Approximately 30% of FDA-approved drugs display atropisomerism, with the figure rising to 80% in certain classes like kinase inhibitors. Developing atropisomers as single, stable isomer presents a compelling opportunity for small molecule manufacturing, enabling scalable production from clinical to commercial stages through advanced technologies and expertise.
In this webinar, a three-fold strategy will be discussed that includes technologies for which SK pharmteco has extensive experience:
- Construction of biaryl moieties using Suzuki couplings, integral structural components in most atropisomers.
- Separation of the enantiomers using Simulated Moving Bed (SMB) chromatography.
- Racemization of the undesired enantiomer under continuous flow conditions, coupled with separation of the enantiomers using SMB.
Speaker:
John Jacobsen, Ph.D.
John Jacobsen is the Head of the Process R&D Group at SK pharmteco Small Molecule NA. John oversees R&D activities at the organization’s two small molecule manufacturing facilities in California and Texas, focusing on the development and implementation of complex synthetic chemistry within fixed assets. Driven by a strong commitment to safety and quality, John ensures that processes are scaled correctly, right the first time, to meet clients’ timelines reliably.
John has extensive experience in developing and scaling synthetic routes for APIs and pharmaceutical intermediates, as well as managing CGMP manufacturing across all clinical and commercial stages—from 5 L kilo batches to 4,000-gallon commercial campaigns. John plays a key role in transferring existing commercial synthetic processes to fixed assets and in developing scalable processes from medicinal chemistry routes.
John holds a Ph.D. in Organic Chemistry and a BS in Biochemistry and Molecular Biology from University of California, Davis.