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Synthesis of a stable‐isotope‐labeled biotinylated pentasaccharide conjugate (EP217609), a dual‐effect anticoagulant drug
Author(s) -
Richard Sébastien,
El Hadri Ahmed,
Goedheijt Marcel Schreuder,
Heisen Michel,
Vader Jan,
Wiegerinck Peter,
Petitou Maurice
Publication year - 2011
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1900
Subject(s) - chemistry , amidine , hydrogenolysis , yield (engineering) , amine gas treating , conjugate , lysine , chromatography , combinatorial chemistry , stereochemistry , catalysis , organic chemistry , biochemistry , amino acid , mathematical analysis , materials science , mathematics , metallurgy
EP217609 is a neutralizable dual‐effect anticoagulant under clinical investigation in cardiopulmonary bypass during cardiac surgery. Stable‐isotope‐labeled EP217609 was synthesized as an internal standard for mass spectrometry in support of bioassays. EP217609 was obtained in six steps starting from three building blocks in an overall yield of 42%, with a chemical purity of >99%. Thus, coupling between the N‐protected labeled biotin‐lysine 4 , prepared in three steps from [ 13 C, 15 N]‐ l ‐lysine 2 , and the pentasaccharide‐spacer‐amine 6 was first performed. Removal of the Cbz protective group to 8 followed by coupling of the activated peptidomimetic building‐block 10 gave the immediate precursor of EP217609, which could be obtained after catalytic hydrogenolysis of 1,2,4‐oxadiazol‐5(2 H )‐one into amidine.