"Pílula da felicidade": síntese e legado da Fluoxetina
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Data
2021-03-02
Autores
Ganéo Neto, Laerte
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Prozac® é o nome comercial dado ao cloridrato de fluoxetina, um medicamento antidepressivo de origem sintética pertencente à classe dos inibidores seletivos da recaptação de serotonina (ISRS). Ele foi desenvolvido nos laboratórios da Eli Lilly na década de 70 e inserido no mercado em 1988, sendo o primeiro de sua classe a ser comercializado nos Estados Unidos. O antidepressivo teve seu auge de vendas em 1998, quando o valor arrecadado atingiu a marca dos 2,8 bilhões de dólares. O seu sucesso foi tamanho, que com o passar dos anos, os seus diversos derivados foram sendo também inseridos no mercado, como a atomoxetina (Strattera®), utilizada no tratamento do Transtorno do Déficit de Atenção com Hiperatividade (TDAH), e a duloxetina (Cymbalta®), indicada para tratar o Transtorno de Ansiedade Generalizada. Ao contrário do Prozac®, que é comercializado na forma racêmica, os seus derivados são comercializados na forma enantiomericamente pura. A rota sintética original da fluoxetina utiliza como material de partida a acetofenona e conta com seis etapas, utilizando diferentes reações como: condensação, redução e substituição, apresentando um rendimento global de 32%. Além dessa rota, existem diversas outras estratégias descritas na literatura para a síntese da fluoxetina e dos seus derivados, que abrangem desde reações enantiosseletivas famosas como a epoxidação assimétrica de Sharpless, até reações mais sustentáveis, envolvendo biocatálise.
Prozac® is the commercial name given to fluoxetine hydrochloride, an antidepressant of synthetic origin which belongs to the selective serotonin reuptake inhibitor (SSRI) class. It was developed in Eli Lilly’s laboratories in the 70’s and inserted in the market in 1988, being the first of its class to be marketed in the United States. The antidepressant had its peak sales in 1998, when the amount collected reached the mark of 2.8 billion dollars. Its success was so great, that over the years, several derivatives were also introduced in the market, such as atomoxetine (Strattera®), used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and duloxetine (Cymbalta®), indicated to treat Generalized Anxiety Disorder. Unlike Prozac®, which is sold as a racemate, its derivatives are marketed in enantiomerically pure form. The original synthetic route of fluoxetine uses acetophenone as starting material and has six stages, using different reactions such as condensation, reduction and substitution, presenting an overall yield of 32%.In addition to this route, there are several other strategies described in the literature for the synthesis of fluoxetine and its derivatives, which range from famous enantioselective reactions, such as Sharpless asymmetric epoxidation, to more sustainable reactions, involving biocatalysis.
Prozac® is the commercial name given to fluoxetine hydrochloride, an antidepressant of synthetic origin which belongs to the selective serotonin reuptake inhibitor (SSRI) class. It was developed in Eli Lilly’s laboratories in the 70’s and inserted in the market in 1988, being the first of its class to be marketed in the United States. The antidepressant had its peak sales in 1998, when the amount collected reached the mark of 2.8 billion dollars. Its success was so great, that over the years, several derivatives were also introduced in the market, such as atomoxetine (Strattera®), used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and duloxetine (Cymbalta®), indicated to treat Generalized Anxiety Disorder. Unlike Prozac®, which is sold as a racemate, its derivatives are marketed in enantiomerically pure form. The original synthetic route of fluoxetine uses acetophenone as starting material and has six stages, using different reactions such as condensation, reduction and substitution, presenting an overall yield of 32%.In addition to this route, there are several other strategies described in the literature for the synthesis of fluoxetine and its derivatives, which range from famous enantioselective reactions, such as Sharpless asymmetric epoxidation, to more sustainable reactions, involving biocatalysis.
Descrição
Palavras-chave
Prozac®, Fluoxetina, Antidepressivo, Síntese assimétrica, Síntese orgânica