The manuscript is dedicated to Prof. Laschat at the occasion of her 60th birthday
– thanks Sabine.
Abstract
The different topics and synthetic approaches in an isotope chemistry laboratory of
a pharma company are described. Besides the challenges in the synthesis of long-lived
isotopes such as 3H or 14C, short-lived isotopes such as 68Ga and stable isotopes such as 15N, 13C or 2H approaches for the isotopic labeling are also demonstrated. Furthermore, method
development with emphasis on collaborations with academic groups to tackle the future
challenges are discussed.
1 Introduction
2 Isotopic Labeling with Hydrogen Isotopes Deuterium (2H, D) and Tritium (3H, T)
2.1 Deuterium Labeling for MS Standards
2.1.1 Labeled Nitrosamines – The Hunt to Quantify Hazardous Impurities
2.1.2 Deuterated Drugs, an Approach To Improve Existing Drugs or To Find Opportunities
in Drug Discovery
2.2 Tritium-Labeling Methods – The Fast Approach to Radioactively Labeled Compounds
2.2.1 Hydrogen Isotope Exchange by Iridium Catalysis
2.2.2 Ruthenium-Catalyzed HIE
2.2.3 Nanoparticles as Catalysts in HIE
2.2.4 Photoredox-Catalyzed HIE
2.2.5 HIE via Classical Radical Mechanism
2.2.6 Beyond HIE – Halogen–Tritium Exchange
3 Challenges in 14C-Synthesis Projects
4 Short-Lived Isotopes – The Need for Speed
5 Beyond Isotope Science – Late-Stage Functionalization
5.1 Examples of Late-Stage Functionalization for Peptides
5.2 Examples of Catalyst-Controlled Late-Stage Functionalization
6 Conclusion
Key words
isotope science - drug discovery - isotope exchange - CH functionalization - catalysis
