Fenfluramine, synthesis

The amphetamine analogue fenfluramine, whose synthesis you designed while you were reading Chapter 31, used to be marketed as an anorectic (appetite-suppressant)—it stimulates the production of the hormone serotonin and makes the body feel satisfied—until it became clear that some undesirable side-effects could be avoided by administering it solely as the (S)-enantiomer. Fenfluramine relaunched as the enantiomerically pure dexfenfluramine, and was reputedly a turning point for your overweight patients —was available in the USA as a component of the slimming pill Redux. 

Resolution of compounds made as diastereoisomeric mixtures The synthesis of Jacobsen s Mn(III) epoxidation catalyst by resolution Resolution with half an equivalent of resolving agent Physical Separation of Enantiomers Chromatography on chiral columns Resolution of triazole fungicides by HPLC A commercial drug separation by chiral HPLC Differential Crystallisation or Entrainment of Racemates Conglomerates and racemic compounds Typical procedure for differential crystallisation (entrainment) Conventional resolution ofL-methyl DOPA Resolution ofL-methyl DOPA by differential crystallisation Finding a differential crystallisation approach to fenfluramine Resolution with Racemisation... 

The synthesis of Fenfluramine (21), a drug acting on the central nervous system, illustrates two amine disconnections. The ethyl group can be removed by the amide method leaving the branched chain primary amine (22) available from the ketone (23) by the oxime method. 

Following is an outline for a synthesis of the anorexic (appetite suppressant) fenfluramine. This compound was one of the two ingredients in Phen-Fen, a weight-loss preparation now banned because of its potential to cause irreversible heart valve damage. 

Welch JT, Lim DS (2007) The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine. Biooig Med Chem 15 6659-6666... 

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