Synthesis of the major metabolites of paroxetine.
Paroxetine is a well-known antidepressant, used worldwide in therapeutics. In comparison with other selective serotonin reuptake inhibitors, it exhibits the highest activity in serotonin reuptake inhibition. Paroxetine metabolism initially involves its demethylenation to the catechol intermediate, which is then O-methylated at positions C3 or C4. Herein, the chemistry resulting in the syntheses of these metabolites (3S,4R)-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine and (3S,4R)-4-(4-fluorophenyl)-3-(4-hydroxy-3-methoxyphenoxymethyl)piperidine is described starting from the common intermediate (3S,4R)-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine. Additionally, the common intermediate was used to synthesize paroxetine, which had the same structure and stereochemistry as commercial paroxetine, thereby confirming our synthetic route.
Segura
Mireia
M
Pharmacology Research Unit, IMIM, 08003 Barcelona, Spain.
Roura
Lidia
L
de la Torre
Rafael
R
Joglar
Jesús
J
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000378:metabolism*; D006801:Humans; D017374:Paroxetine / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism*; D013237:Stereoisomerism
D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors