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A quantitative approach to predicting rate constants for aqueous racemization allows pointless stereoselective syntheses to be avoided.

Ballard, A and Ahmad, HO and Narduolo, S and Rosa, L and Chand, N and Cosgrove, DA and Varkonyi, P and Asaad, N and Tomasi, S and Buurma, NJ and Leach, AG (2017) A quantitative approach to predicting rate constants for aqueous racemization allows pointless stereoselective syntheses to be avoided. Angewandte Chemie International Edition. ISSN 1521-3773

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Abstract

Racemisation has a large impact upon the biological properties of molecules but the chemical scope of compounds with known rate constants for racemisation in aqueous conditions was hitherto limited. To address this remarkable blind spot, we have measured the kinetics for racemisation of 28 compounds using circular dichroism and 1H NMR spectroscopy. We show that rate constants for racemisation (measured by ourselves and others) correlate well with deprotonation energies from quantum mechanical (QM) and group contribution calculations. Such calculations thus provide predictions of the second-order rate constants for general-base-catalyzed racemisation that are usefully accurate. When applied to recent publications describing the stereoselective synthesis of compounds of purported biological value, the calculations reveal that racemisation would be sufficiently fast to render these expensive syntheses pointless.

Item Type: Article
Additional Information: This is the accepted version of the following article: Ballard, A., Ahmad, H. O., Narduolo, S., Rosa, L., Chand, N., Cosgrove, D. A., Varkonyi, P., Asaad, N., Tomasi, S., Buurma, N. J. and Leach, A. G. (), A quantitative approach to predicting rate constants for aqueous racemization allows pointless stereoselective syntheses to be avoided. Angew. Chem. Int. Ed.. Accepted Author Manuscript. doi:10.1002/anie.201709163, which has been published in final form at http://dx.doi.org/10.1002/anie.201709163
Uncontrolled Keywords: 03 Chemical Sciences
Subjects: Q Science > QD Chemistry
Q Science > QR Microbiology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Related URLs:
Date Deposited: 31 Oct 2017 12:10
Last Modified: 31 Oct 2017 12:10
DOI or Identification number: 10.1002/anie.201709163
URI: http://researchonline.ljmu.ac.uk/id/eprint/7450

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