34S: A New Opportunity for the Efficient Synthesis of Stable Isotope Labeled Compounds

Abstract The synthesis of stable isotope labeled (SIL) complex drug molecules with a ≥3 mass unit increase from the parent compound is essential for drug discovery and development. Typical approaches that rely on 2 H, 13 C, and 15 N isotopes can be very challenging or even intractable, and can delay the drug development process. This work introduces a new concept for the synthesis of labeled compounds that relies on the use of 34 S. The synthetic utility of 34 S was demonstrated with the efficient synthesis of [ 34 S]phosphorothioates [ 34 S 2 ]‐PS‐ODNs‐TTT and [ 13 C, 15 N, 34 S]‐ceftolozane. In addition, a procedure for the direct oxidation of phosphites to [ 34 S]phosphorothioates using elemental 34 S without isotope dilution was developed.