In this section
@article{Zhong:2024:10.1002/ange.202420028,
author = {Zhong, Z and Hocking, BJW and Brown, CP and Ma, T and White, AJP and Mann, DJ and Armstrong, A and Bull, JA},
doi = {10.1002/ange.202420028},
journal = {Angewandte Chemie},
title = {Synthesis and Functionalization of SulfoximineBicyclo[1.1.0]butanes: Functionalizable, Tuneable and CysteineSelective Chiral Warheads},
url = {http://dx.doi.org/10.1002/ange.202420028},
year = {2024}
}
TY - JOUR
AB - <jats:title>Abstract</jats:title><jats:p>Electrophilic covalent warheads with appropriate reactivity and selectivity are crucial to the investigation of protein function and the discovery of therapeutics. Here we report the synthesis of sulfoximine bicyclo[1.1.0] butanes (BCBs) as novel thiol reactive chiral warheads, achieved in onepot from methylsulfoximines. Unusually the warhead can then be derivatized, keeping the BCB intact, over 3 vectors: i) sulfoximine Nmodification instills a broad range of strainrelease reactivity; ii) sp<jats:sup>2</jats:sup>crosscoupling reactions on arylBCBsulfoximines allows direct diversification, and iii) functionalization of the BCB motif itself is achieved by metalation and trapping with electrophiles. The BCB sulfoximines are shown to react selectively with cysteine including in a protein model (CDK2) under biocompatible conditions. Preliminary data indicate suitability for chemoproteomic applications, and enantioselective cysteinelabelling. The reactivity of sulfoximine BCBs with electron withdrawing groups on nitrogen is comparable to acrylamides with low to moderate reactivity.</jats:p>
AU - Zhong,Z
AU - Hocking,BJW
AU - Brown,CP
AU - Ma,T
AU - White,AJP
AU - Mann,DJ
AU - Armstrong,A
AU - Bull,JA
DO - 10.1002/ange.202420028
PY - 2024///
SN - 0044-8249
TI - Synthesis and Functionalization of SulfoximineBicyclo[1.1.0]butanes: Functionalizable, Tuneable and CysteineSelective Chiral Warheads
T2 - Angewandte Chemie
UR - http://dx.doi.org/10.1002/ange.202420028
UR - https://doi.org/10.1002/ange.202420028
ER -
Interested in studying a PhD at the Department of Life Sciences? Find out more about postgraduate research opportunties.