Vinyl sulfoximines offer an easily made, tunable warhead class for covalent drugs

  • A gentle one-pot oxidative route converts easily prepared beta-chlorosulfides into a wide range of vinyl sulfoximines, tolerating many functional groups with workable yields.
  • Reaction-rate studies using amino acid models showed a clear bias toward thiol partners over other nucleophilic side chains.
  • Quantitative structure-reactivity trends let chemists dial electrophilicity up or down, positioning the S(VI) motif as a rational option for covalent inhibitor design.
💡 Points Based on the abstract

Interesting as an acrylamide alternative, mainly because the sulfoximine nitrogen is a free handle: N-substituents should tune both electrophilicity and physchem, and the stereogenic S is another lever. Thiol bias is encouraging, but amino acid models aren't proteome-wide. The proof will be GSH half-lives and intrinsic kinact/KI against acrylamides on a real kinase.

A One-Pot Synthesis of Vinyl Sulfoximines and Their Kinetic Evaluation as Tunable Covalent Warheads ↗