Bioorthogonal Retro-Cope Elimination Reaction of N, N-Dialkylhydroxylamines and Strained Alkynes

J Am Chem Soc. 2021 Apr 21;143(15):5616-5621. doi: 10.1021/jacs.1c00885. Epub 2021 Apr 8.

Abstract

A bioorthogonal reaction between N,N-dialkylhydroxylamines and cyclooctynes is described. This reaction features a highly regioselective transformation between small, easily functionalizable reaction components with second-order rate constants reaching 84 M-1 s-1. The reaction is orthogonal to the inverse-electron demand Diels-Alder reactions between tetrazine and strained alkenes, and its components exhibit exquisite stability and chemoselectivity in cell lysate. This retro-Cope elimination reaction introduces a new member to the bioorthogonal reaction compendium outside the prolific class of cycloaddition reactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry
  • Alkynes / chemistry*
  • Cycloaddition Reaction
  • Green Fluorescent Proteins / chemistry
  • HeLa Cells
  • Humans
  • Hydroxylamines / chemistry*
  • Microscopy, Confocal
  • Muramidase / chemistry
  • Stereoisomerism
  • Tetrazoles / chemistry

Substances

  • Alkenes
  • Alkynes
  • Hydroxylamines
  • Tetrazoles
  • Green Fluorescent Proteins
  • Muramidase