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

The synthesis of stable isotope labeled (SIL) complex drug molecules with >= 3 mass unit increase from the parent compound is essential for drug discovery and development. Typical approaches that rely on H-2, C-13, and N-15 isotopes can be very challenging or even intractable, and can delay the d...

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Published inChemistry : a European journal Vol. 24; no. 28; pp. 7133 - 7136
Main Authors Ren, Sumei, Fier, Patrick S., Ren, Hong, Hoover, Andrew J., Hesk, David, Marques, Rosemary, Mergelsberg, Ingrid
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 17.05.2018
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
isotopic labeling
C-13
RNA
PHOSPHOROTHIOATES
absolute bioavailability
SOLID-PHASE
SULFUR
oligonucleotides
solid-phase synthesis
sulfur-34
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Summary:The synthesis of stable isotope labeled (SIL) complex drug molecules with >= 3 mass unit increase from the parent compound is essential for drug discovery and development. Typical approaches that rely on H-2, C-13, and N-15 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 S-34. The synthetic utility of S-34 was demonstrated with the efficient synthesis of [S-34]phosphorothioates [S-34(2)]-PS-ODNs-TTT and [C-13, N-15, S-34]-ceftolozane. In addition, a procedure for the direct oxidation of phosphites to [S-34]phosphorothioates using elemental S-34 without isotope dilution was developed.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201801494