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

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 S2 ]-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.