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34 S: A New Opportunity for the Efficient Synthesis of Stable Isotope Labeled Compounds
Author(s) -
Ren Sumei,
Fier Patrick S.,
Ren Hong,
Hoover Andrew J.,
Hesk David,
Marques Rosemary,
Mergelsberg Ingrid
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201801494
Subject(s) - chemistry , isotope , stable isotope ratio , combinatorial chemistry , molecule , isotope dilution , radiochemistry , organic chemistry , mass spectrometry , chromatography , physics , quantum mechanics
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.