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Absolute configuration of (+)‐α‐dihydrotetrabenazine, an active metabolite of tetrabenazine
Author(s) -
Kilbourn Michael R.,
Lee Lihsueh C.,
Heeg Mary J.,
Jewett Douglas M.
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:1<59::aid-chir11>3.0.co;2-p
Subject(s) - tetrabenazine , chemistry , enantiomer , stereochemistry , absolute configuration , active metabolite , metabolite , biochemistry , biology , dopamine , neuroscience
Chiral column liquid chromatography and enantiospecific enzymatic hydrolysis were utilized to separate the enantiomers of α‐ and β‐dihydrotetrabenazine and α‐9‐O‐desmethyldihydrotetrabenazine, three benzo[a]quinolizines derived from the amine‐depleting drug tetrabenazine. An X‐ray crystal structure analysis of (−)‐α‐9‐O‐desmethyldihydrotetrabenazine gave an absolute structure of that compound as the 2 S , 3 S , 11b S isomer. Therefore, (−)‐α‐dihydrotetrabenazine also has the 2 S , 3 S , 11b S absolute configuration. (+)‐α‐Dihydrotetrabenazine, the single biologically active isomer from the metabolic reduction of tetrabenazine, thus has the absolute configuration of 2 R , 3 R , 11b R . For further in vitro and in vivo studies of the vesicular monoamine transporter, it is now possible to use the single enantiomer of radiolabeled α‐dihydrotetrabenazine. Chirality 9:59–62, 1997. © 1997 Wiley‐Liss, Inc.