Atropisomerism is a potentially dynamic form of chirality that is ubiquitous throughout drug discovery, most prominently as a rapidly interconverting racemate. While rapidly interconverting atropisomers are not typcally dealt with as chiral, they will in fact bind their targets in single atropisomer form. Herein we will discuss our efforts towards exploiting atropsiomer conformation as a way to modulate the selectivity profile of promiscuous kinase inhibitors. These endeavors inspired the development of several new regio- and enantioselective methodologies that proved to be crucial for our studies on atropisomerism, of which a kinetic resolution that affords direct access to atropisomerically pure kinase inhibitors will be discussed.

Atropisomerism as a means to modulate target selectivity and an inspiration for new chemistry

255th National Meeting (2018)

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