Gavriel, Alexander G;
Leroux, Flavien;
Khurana, Gurjeet S;
Lewis, Viliyana G;
Chippindale, Ann M;
Sambrook, Mark R;
Hayes, Wayne;
(2021)
Self-Immolative System for Disclosure of Reactive Electrophilic Alkylating Agents: Understanding the Role of the Reporter Group.
The Journal of Organic Chemistry
, 86
(15)
pp. 10263-10279.
10.1021/acs.joc.1c00996.
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Abstract
The development of stable, efficient chemoselective self-immolative systems, for use in applications such as sensors, requires the optimization of the reactivity and degradation characteristics of the self-immolative unit. In this paper, we describe the effect that the structure of the reporter group has upon the self-immolative efficacy of a prototype system designed for the disclosure of electrophilic alkylating agents. The amine of the reporter group (a nitroaniline unit) was a constituent part of a carbamate that functioned as the self-immolative unit. The number and position of substituents on the nitroaniline unit were found to play a key role in the rate of self-immolative degradation and release of the reporter group. The position of the nitro substituent (meta- vs para-) and the methyl groups in the ortho-position relative to the carbamate exhibited an influence on the rate of elimination and stability of the self-immolative system. The ortho-methyl substituents imparted a twist on the N–C (aromatic) bond leading to increased resonance of the amine nitrogen’s lone pair into the carbonyl moiety and a decrease of the leaving character of the carbamate group; concomitantly, this may also make it a less electron-withdrawing group and lead to less acidification of the eliminated β-hydrogen.
| Type: | Article |
|---|---|
| Title: | Self-Immolative System for Disclosure of Reactive Electrophilic Alkylating Agents: Understanding the Role of the Reporter Group |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.joc.1c00996 |
| Publisher version: | https://doi.org/10.1021/acs.joc.1c00996 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10176302 |
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