Iterative Catalyst-Controlled Diastereoselective Matteson Homologations Enable the Selective Synthesis of Benzestrol Isomers
We report the development of an iterative Matteson homologation reaction with catalyst-controlled diastereoselectivity through the design of a new catalyst. This reaction was applied to the selective synthesis of each stereoisomer of benzestrol, a bioactive compound with estrogenic activity featuring three contiguous stereocenters. The different stereoisomers were assayed to determine their binding affinity for the estrogen receptor α (ERα), and the absolute configuration of the compound having uniquely high activity was determined. This research lays a framework for the catalytic synthesis and study of complete stereoisomeric sets of other bioactive molecules and chemical probes containing contiguous stereocenters.
Authors
- K.W. Nettles (ORCID: https://orcid.org/0000-0003-2917-7574)
- Eric N. Jacobsen (ORCID: https://orcid.org/0000-0001-7952-3661)
- John A. Katzenellenbogen (ORCID: https://orcid.org/0000-0003-0914-0010)
- Benita S. Katzenellenbogen (ORCID: https://orcid.org/0000-0002-8847-2752)
- Jerome C. Nwachukwu (ORCID: https://orcid.org/0000-0003-4313-9187)
- Hayden A. Sharma (ORCID: https://orcid.org/0000-0003-3894-9118)
- Yingwei Hou (ORCID: https://orcid.org/0000-0003-0591-8753)
- Kathryn E. Carlson
- Steven R. Angle (ORCID: https://orcid.org/0009-0009-9769-4806)
- Chan K. Choi (ORCID: https://orcid.org/0009-0002-4005-5367)
- Sung Hoon Kim (ORCID: https://orcid.org/0000-0002-1344-5653)
Institutions
- Harvard University (US)
- University of Illinois Urbana-Champaign (US)
- The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1021/jacs.4c12857
- Citations
- 8
- Primary Topic
- Chemical Synthesis and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- Breast Cancer Research Foundation
- National Institutes of Health
- National Cancer Institute
- National Institute of General Medical Sciences