High-Complexity Atropisomeric Macrocycle

The publication describes the complete synthetic route redesign of AZD5991, one of the most complex APIs in AstraZeneca’s small molecule development portfolio to date. The teams worked together to explore a range of routes to key heterocyclic fragments, utilising high-throughput experimentation to identify hits and optimise processes quickly.

Authors: Gareth P. Howell, Lauren R. Agnew, Christoph Bauer, Fiona J. Bell, Andrew D. Campbell, Kuangchu Dai, David Dave, Sam R. Ellis, Matthew J. Foulkes, Malcolm A. Y. Gall, Kilian Garrec, Huajun Ge, Barry R. Hayter, Martin F. Jones, George Karageorgis, Mairi Littleson, Thomas W. Lloyd-Hughes, Harriet C. McNicholl, David T. Mooney, Bethany J. Moore, Rachel H. Munday, Emily Noone, David Perkins, Lyn Powell, Okky Dwichandra Putra, Simone Tomasi, Miriam Turner, Hongxu Wang, Hucheng Zhao, Oliver T. Ring

Organic Letters 2025, 1083-6160

DOI: 10.1021/acs.oprd.4c00524

Access the publication at https://pubs.acs.org/doi/10.1021/acs.oprd.4c00524