title: Synthesis of the major metabolites of paroxetine.
abstract: 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.
authors.affiliation: Pharmacology Research Unit, IMIM, 08003 Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Segura
authors.forename: Lidia
authors.initials: L
authors.lastname: Roura
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.forename: Jesús
authors.initials: J
authors.lastname: Joglar
mesh_terms: 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
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors