Korsik, M;
Tse, EG;
Smith, DG;
Lewis, W;
Rutledge, PJ;
Todd, MH;
(2020)
tele-Substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials.
The Journal of Organic Chemistry
, 85
(21)
pp. 13438-13452.
10.1021/acs.joc.0c01045.
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Abstract
We have discovered and studied a tele-substitution reaction in a biologically important heterocyclic ring system. Conditions that favor the tele-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base or the use of softer nucleophiles, less polar solvents, and larger halogens on the electrophile. Using results from X-ray crystallographic and isotope labeling experiments, a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the in vivo active antiplasmodium compounds of Series 4 of the Open Source Malaria consortium.
| Type: | Article |
|---|---|
| Title: | tele-Substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.joc.0c01045 |
| Publisher version: | https://doi.org/10.1021/acs.joc.0c01045 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. |
| Keywords: | Hydrocarbons, Substitution reactions, Chemical reactions, Aromatic compounds, Solvents |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10114909 |
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