ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
2 files

Synthesis and Configurational Assignment of Vinyl Sulfoximines and Sulfonimidamides

preprint
submitted on 12.02.2021, 09:43 and posted on 15.02.2021, 04:40 by Gregory Craven, Edward L. Briggs, Charlotte Zammit, Alex McDermott, Stephanie Greed, Dominic Affron, Charlotte Leinfellner, Hannah Cudmore, Ruth Tweedy, Renzo Luisi, James Bull, Alan Armstrong
Vinyl sulfones and sulfonamides are valued for their use as electrophilic warheads in covalent protein inhibitors. Conversely, the S(VI) aza-isosteres thereof, vinyl sulfoximines and sulfonimidamides, are far less studied and have yet to be applied to the field of protein bioconjugation. Herein, we report a range of different synthetic methodologies for constructing vinyl sulfoximine and vinyl sulfonimidamide architectures that allows access to new areas of electrophilic chemical space. We demonstrate how late stage functionalization can be applied to these motifs to incorporate alkyne tags, generating fully functionalized probes for future chemical biology applications. Finally, we establish a workflow for determining the absolute configuration of enantioenriched vinyl sulfoximines and sulfonimidamides by comparing experimentally and computationally determined electronic circular dichroism spectra, enabling access to configurationally assigned enantiomeric pairs by separation.

History

Email Address of Submitting Author

g.craven13@gmail.com

Institution

University of Leeds

Country

United Kingdom

ORCID For Submitting Author

0000-0003-3414-8348

Declaration of Conflict of Interest

No conflict of interest

Exports