An efficient chemoenzymatic route to the antidepressants (R)-fluoxetine and (R)-tomoxetine.
(S)-1-Phenyl-3-buten-1-ol (1), prepared in high optical purity by enzymatic resolution of the racemate, is a convenient building block for the synthesis of (R)-fluoxetine (7a) and (R)-tomoxetine (7b). Compound 1 was converted to the title drugs by etherification with appropriate phenols under Mitsunobu conditions, ozonolysis of the terminal double bond, mesylation of the resulting alcohol and substitution with methylamine.
Bracher
F
F
Institut für Pharmazeutische Chemie, Technischen Universität Braunschweig, Germany.
Litz
T
T
D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000069445:Atomoxetine Hydrochloride; D004798:Enzymes / Q000737:chemistry; D005473:Fluoxetine / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D011437:Propylamines / Q000138:chemical synthesis* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D000928:Antidepressive Agents; D004798:Enzymes; D011437:Propylamines; D005473:Fluoxetine; D000069445:Atomoxetine Hydrochloride