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The synthesis of deuterium labelled metabolites of warfarin and phenprocoumon
Author(s) -
Heimark L. D.,
Toon S.,
Low L. K.,
Swinney D. C.,
Trager W. F.
Publication year - 1986
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.2580230204
Subject(s) - chemistry , alkylation , hydrolysis , methanol , yield (engineering) , 4 hydroxycoumarin , organic chemistry , deuterium , materials science , physics , quantum mechanics , metallurgy , catalysis
The synthesis of deuterium labelled 4′‐,6‐,7‐ and 8‐hydroxy metabolites of warfarin and phenprocoumon is described. The pentadeuterio labelled 6‐,7‐ and 8‐hydroxyphenprocoumons were prepared via alkylation of the respective 6‐, 7‐ and 8‐methoxy‐4‐hydroxycoumarins with 1‐(phenyl‐d 5 )‐1‐bromopropane and subaequent cleavage of the methyl protecting group with boron tribromide. The synthesis of 1‐(pentadeuteriophenyl)‐1‐bromopropane and the 6‐, 7‐ and 8‐methoxy‐4‐hydroxy‐coumarins are also presented. The pentadeuterio labelled 6‐, 7‐ and 8‐hydroxy‐warfarins were obtained by reaction of 4‐(phenyl‐d 5 )‐3‐buten‐2‐one with the respective 6‐, 7‐ and 8‐hydroxy‐4‐hydroxycoumarins in methanol followed by hydrolysis of the intermediate cyclic methyl ketals in aqueous acid. 4‐Hydroxycoumarin‐5,6,7,8‐d 4 , prepared from phenyl‐d 6 and tetradeuteriomalonic acid, was reacted with 1‐(p‐hydroxyphenyl)‐1‐propanol and 4‐(p‐hydroxyphenyl)‐3‐buten‐2‐one to yield labelled 4′‐hydroxyphenprocoumon and 4′‐hydroxywarfarin respectively.