Tools
Tools
Ballard, A, Ahmad, HO, Narduolo, S, Rosa, L, Chand, N, Cosgrove, DA, Varkonyi, P, Asaad, N, Tomasi, S, Buurma, NJ and Leach, AG (2017) Quantitative Prediction of Rate Constants for Aqueous Racemization To Avoid Pointless Stereoselective Syntheses. Angewandte Chemie International Edition, 57 (4). pp. 982-985. ISSN 1521-3773
|
Text
Manuscript.pdf - Accepted Version Download (847kB) | Preview |
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: | 04 Sep 2021 11:03 |
| DOI or ID number: | 10.1002/anie.201709163 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/7450 |
 |
View Item |