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Synthesis of 13 C warfarin labelled at the hemiketal carbon, and its resolution
Author(s) -
Savell Van Henry,
Valente Edward J.,
Eggleston D. S.
Publication year - 1989
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.2580270605
Subject(s) - chemistry , diastereomer , enantiomer , warfarin , stereochemistry , 4 hydroxycoumarin , anomer , organic chemistry , medicine , cardiology , catalysis , atrial fibrillation
Warfarin (cyclic hemiketal form: 2‐hydroxy‐2‐methyl‐4‐phenyl‐3,4‐dihydro‐2 H ,5 H ‐pyrano[3,2‐c][1]benzopyran‐5‐one) is labeled with 98+% 13 C at the anomeric carbon (C2) and resolved into its enantiomers. Acetone‐2‐ 13 C(98.6%) condenses with benzaldehyde in aqueous base to produce 4‐phenyl‐3‐buten‐2‐one‐2‐ 13 C(98+%). Michael‐type addition of this to 4‐hydroxycoumarin in methanol produces the labeled diastereomeric warfarin methyl ketals which on deprotection form racemic warfarin‐2‐ 13 C(98+%). Classical resolution of labeled warfarin with quinidine produces partly resolved (S)‐(–)‐warfarin‐2‐ 13 C(98+%). Labeled warfarin is a suitable probe for warfarin configuration for which three distinct isomeric forms are known.