Umpolung Phosphorylation of Tyrosine via 1,2-Phospha-Brook Rearrangement

Org Lett. 2024 Oct 18;26(41):8827-8831. doi: 10.1021/acs.orglett.4c03223. Epub 2024 Oct 10.

Abstract

Phosphorylated tyrosine is a fundamental building block of bioactive peptides and proteins. However, the chemoselective phosphorylation of tyrosine over other nucleophilic amino acid residues in unprotected peptides remains a significant challenge. Here we report an umpolung strategy that converts the C-terminal tyrosine into an electrophilic spirolactone cyclohexadienone motif through hypervalent iodine oxidation, followed by a 1,2-phospha-Brook rearrangement using phosphite diesters as nucleophilic phosphoryl donors. This reaction proceeds chemoselectively at the tyrosine phenol and is applicable to a wide range of peptide substrates containing various nucleophilic amino acid residues, including serine and threonine.

MeSH terms

  • Molecular Structure
  • Oxidation-Reduction
  • Peptides / chemistry
  • Phosphites / chemistry
  • Phosphorylation
  • Tyrosine* / chemistry

Substances

  • Tyrosine
  • Peptides
  • Phosphites