Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Regular Articles
Hydrogen–Deuterium (H–D) Exchange Reaction of Warfarin in D2O Solution
Chisato TodeAtsuko TakeuchiSeigo IwakawaAkitoshi TatsumiMakiko Sugiura
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2009 年 57 巻 7 号 p. 653-656

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To prove the presence of a hydrogen–deuterium (H–D) exchange reaction, 1H- and 13C-NMR spectra of warfarin were measured in solvents containing D2O and H2O. In D2O or D2O/dimethyl sulfoxide (DMSO)-d6 solvent, signal pattern changes were observed on H12 and H11 as well as 14 methyl protons over time while no changes were observed on H2O or H2O/DMSO-d6 solvent. The observed changes in the solvents containing D2O were concluded to be caused by the H–D exchange reaction on H12, the process of CH2→CHD→CD2. MS spectroscopy also confirmed these H–D exchanges. The kinetics of this reaction were analyzed as the successive reaction, and the mechanism was also proposed.
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© 2009 The Pharmaceutical Society of Japan
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