Development of an atropselective methodology for axially chiral biaryls in the asymmetric synthesis of A-240610.0.
A-240610.0 is a novel non-steroidal glucocorticoid receptor-selective ligand. It has demonstrated an anti-inflammatory activity equivalent to that of the synthetic glucocorticoids, and has shown an improved side-effects profile in vivo. This review will present the process research and development proceeding from the initial racemic route to an efficient asymmetric process. This process relied on the development of a novel atropselective synthesis of an axially chiral biaryl to form the critical atropisomer intermediate in good yields (85%) and with high diastereoselectivity (99:1).
Ku
Yi-Yin
YY
Abbott Laboratories, GPRD Process Research, D-R450, Building R-13, 1401 Sheridan Road, North Chicago, IL 60064, USA. yiyin.ku@abbott.com
Grieme
Tim
T
D000818:Animals; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D006801:Humans; D013237:Stereoisomerism; D013678:Technology, Pharmaceutical / Q000379:methods*
C456759:A-240610; D006576:Heterocyclic Compounds, 4 or More Rings