Tritium O-Methylation of N-Alkoxy Maleimide Derivatives as Labeling Reagents for Biomolecules

Martin R. Edelmann, Thorsten Muser

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An efficient procedure to access tritium-labeled maleimide derivatives in a high specific activity has been developed. N-Substituted maleimides containing the hydroxy functionality are O-methylated in a three-step synthesis route, including (1) Diels-Alder protection of the maleimide core, (2) O-methylation by the use of commercially available [3H]methyl nosylate, and (3) deprotection by retro-Diels-Alder reaction. With our procedure, N-hydroxyalkyl maleimide derivatives can be labeled in overall radiochemical yields of 13-15% and in >98% radiochemical purity. The major advantage of N-alkoxy maleimides in comparison to N-alkylated maleimides such as N-ethylmaleimide is their lower volatility, which enables safer handling with respect to radiation-safety protection. Tritium-labeled maleimide building blocks allow subsequent Michael-type conjugation reactions of thiol-containing biomolecules for mechanistic in vitro or in vivo studies.

Original languageEnglish
Pages (from-to)1027-1033
Number of pages7
JournalBioconjugate Chemistry
Issue number5
Early online date28 Apr 2021
Publication statusPublished - 19 May 2021

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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