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Lookup NU author(s): Jude HeedORCiD, Dr Roly ArmstrongORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2023.
For re-use rights please refer to the publisher's terms and conditions.
Atropisomers are molecules whose stereogenicity arises from restricted rotation about a single bond and are of current importance due to their applications in catalysis, medicine, and materials science. The defining feature of atropisomericmolecules is that their stereoisomers may interconvert by bond rotation: as a result, evaluating their configurational stability (i.e., the rate at which their stereoisomers interconvert) is central to any work in this area. Important atropisomeric scaffolds include C–C linked biaryls (such as the ligand BINAP and the drug vancomycin) and C–N linked amine derivatives such as the drug telenzepine. This article focusses upon the three most widely used experimental methods that are available to measure the rate of racemization in atropisomers, namely: (i) kinetic analysis of the racemization of an enantioenriched sample: (ii) dynamic HPLC; and (iii) variable temperature NMR. Foreach technique, an explanation of the theory is set out, followed by a detailed experimental procedure. A discussion is also included of which technique to try when confronted with a new molecular structure whose properties are not yet known. None of the three procedures require complex experimental techniques, and all can be performed using standard analytical equipment (NMR and HPLC). The time taken to determine a racemization rate depends on which experimental method is required, but for a new compound it is generally possible to measure a racemization rate in <1 day.
Author(s): Heeb JP, Clayden J, Smith MD, Armstrong RJ
Publication type: Article
Publication status: Published
Journal: Nature Protocols
Year: 2023
Volume: 18
Pages: 2745–2771
Online publication date: 04/08/2023
Acceptance date: 05/06/2023
Date deposited: 06/06/2023
ISSN (print): 1750-2799
ISSN (electronic): 1754-2189
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41596-023-00859-y
DOI: 10.1038/s41596-023-00859-y
ePrints DOI: 10.57711/3tvb-nf76
Data Access Statement: We have previously reported synthetic procedures and data for compounds 1 (ref. 18), 2 (ref. 11) and 4 (ref. 11), which are used to illustrate all three procedures.
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