Screening for generality in asymmetric catalysis.

Autor: Wagen CC; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA., McMinn SE; Discovery Chemistry, Merck & Co. Inc, Boston, MA, USA., Kwan EE; Process Research and Development, Merck & Co. Inc, Boston, MA, USA. eugene.kwan@merck.com., Jacobsen EN; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA. jacobsen@chemistry.harvard.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Oct; Vol. 610 (7933), pp. 680-686. Date of Electronic Publication: 2022 Sep 01.
DOI: 10.1038/s41586-022-05263-2
Abstrakt: Research in the field of asymmetric catalysis over the past half century has resulted in landmark advances, enabling the efficient synthesis of chiral building blocks, pharmaceuticals and natural products 1-3 . A small number of asymmetric catalytic reactions have been identified that display high selectivity across a broad scope of substrates; not coincidentally, these are the reactions that have the greatest impact on how enantioenriched compounds are synthesized 4-8 . We postulate that substrate generality in asymmetric catalysis is rare not simply because it is intrinsically difficult to achieve, but also because of the way chiral catalysts are identified and optimized 9 . Typical discovery campaigns rely on a single model substrate, and thus select for high performance in a narrow region of chemical space. Here we put forth a practical approach for using multiple model substrates to select simultaneously for both enantioselectivity and generality in asymmetric catalytic reactions from the outset 10,11 . Multisubstrate screening is achieved by conducting high-throughput chiral analyses by supercritical fluid chromatography-mass spectrometry with pooled samples. When applied to Pictet-Spengler reactions, the multisubstrate screening approach revealed a promising and unexpected lead for the general enantioselective catalysis of this important transformation, which even displayed high enantioselectivity for substrate combinations outside of the screening set.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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