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Synthesis of Two Metabolites of the Antiarrythmicum Amiodarone
Author(s) -
Wendt Barbara,
Riem Ha Huy,
Hesse Manfred
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200209)85:9<2990::aid-hlca2990>3.0.co;2-r
Subject(s) - chemistry , metabolite , heteronuclear single quantum coherence spectroscopy , stereochemistry , in vitro , chemical structure , chromatography , nuclear magnetic resonance spectroscopy , organic chemistry , biochemistry
The metabolism of the potent antiarrythmic drug amiodarone (AMI; 1 ) has yet not been fully investigated. Recently, in vitro experiments revealed that in rabbit‐liver microsomes, AMI ( 1 ) and its main metabolite MDEA ( 2 ) were biotransformed to the hydroxylated derivatives 3′‐OH‐AMI ( 3 ) and 3′‐OH‐MDEA ( 4 ), respectively. To establish the chemical structure of 3 and 4 , we developed a total synthesis of these two metabolites of AMI ( 1 ). 1 H‐ and 13 C‐NMR Signal assignment from HSQC and HMBC 2D NMR data of synthesized 4 showed that the proposed structure of metabolite 4 is correct. Even the structure of 3 was found to be correct by comparing its HPLC/MS‐MS/MS with the data described earlier.