100568-02-3Relevant articles and documents
Synthesis, anorexigenic activity and QSAR of substituted aryloxypropanolamines
Srivastava, Shipra,Bhandari, Kalpana,Shankar, Girija,Singh,Saxena, Anil K.
, p. 631 - 642 (2004)
Substituted aryloxypropanolamines (6-20) were synthesized and evaluated for their anorexigenic activity. Among them 4-cyanoaryloxy (7), 2-methylaryloxy (9), 2-methoxyl aryloxy (10), 4-acetamidoaryloxy (15), 4-bromoaryloxy (16) and 4-ethylaminoaryloxy (20) exhibited potent anorexigenic activity. According to QSAR studies, the electronic parameter 'σ' plays an important role in describing the variance in activity. Birkhaeuser Boston 2004.
An asymmetric dihydroxylation route to enantiomerically pure norfluoxetine and fluoxetine
Pandey, Rajesh Kumar,Fernandes, Rodney A.,Kumar, Pradeep
, p. 4425 - 4426 (2002)
An efficient, practical asymmetric synthesis of (R)-norfluoxetine 1 and (R)-fluoxetine 2 has been achieved. The synthetic strategy features a Sharpless asymmetric dihydroxylation (SAD) route to the common building block 1,3-amino alcohol 9, from which (R)-norfluoxetine, (R)-fluoxetine and other related analogs can be synthesized.
Chemoenzymatic Synthesis of Both Enantiomers of Fluoxetine
Chenevert, Robert,Fortier, Genevieve
, p. 1603 - 1606 (1991)
Both enantiomers of fluoxetine have been synthesized from ethyl benzoylacetate.The key step is the enantioselective reduction of the starting material by baker's yeast.
Synthesis of R- and S- fluoxetine, norfluoxetine and related compounds from styrene oxide
Mitchell,Koenig
, p. 1231 - 1238 (1995)
A facile, high yield synthesis of R-- or S--fluoxetine and norfluoxetine is described. This synthetic route utilizes readily available starting materials.
Asymmetric Synthesis of Both Enantiomers of Fluoxetine via Microbiological Reduction of Ethyl Benzoylacetate
Chenevert, Robert,Fortier, Genevieve,Rhlid, Rachid Bel
, p. 6769 - 6776 (1992)
Microbiological reduction of ethyl benzoylacetate by bakers' yeast (Saccharomyces cerevisiae), Beauveria sulfurescens or Geotrichum candidum afforded ethyl (S)-3-hydroxy-3-phenylpropionate in high optical yield.This enantiomerically pure alcohol was converted into both enantiomers of fluoxetine (7).The product resulting from the bakers' yeast reduction had ee values (87-93percent) lower than the 100percent value erroneously attributed in earlier studies.Key Words: Fluoxetine; asymmetric synthesis; bioreduction; bakers' yeast; Beauveria sulfurescens; Geotrichum candidum.
Asymmetric dihydroxylation route to (R)-isoprenaline, (R)-norfluoxetine and (R)-fluoxetine
Kumar, Pradeep,Upadhyay, Rajesh Kumar,Pandey, Rajesh Kumar
, p. 3955 - 3959 (2004)
An efficient asymmetric synthesis of enantiomerically pure (R)-isoprenaline, (R)-norfluoxetine and (R)-fluoxetine is described using Sharpless asymmetric dihydroxylation as the key step.
Enantioselective hydrogenation of β-ketoesters using a MeO-PEG-supported Biphep ligand under atmospheric pressure: A practical synthesis of (S)-fluoxetine
Chai, Liting,Chen, Huansheng,Li, Zhiming,Wang, Quanrui,Tao, Fenggang
, p. 2395 - 2398 (2006)
The preparation of a novel chiral 2,2′-bis(MeO-PEG-supported)-6, 6′-bis(diphenylphosphanyl)biphenyl (MeO-PEG-Biphep) ligand is described. The derived ruthenium complex catalyzes the hydrogenation of β-ketoesters in up to 99% yield and 99% ee under atmospheric pressure. The accelerating effects exerted by the PEG linkage are dramatic when compared to the unsupported analogue, MeO-Biphep-RuBr2. Furthermore, the catalyst can be recovered easily and the recycled catalysts were shown to maintain their efficiency in two consecutive runs, albeit with declining activity. One of the products, (S)-ethyl-3-hydroxy-3-phenylpropanoate, is useful in the preparation of (S)-fluoxetine. Georg Thieme Verlag Stuttgart.
Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats
Cardoso, Juciane Lauren Cavalcanti,Lanchote, Vera Lucia,Pereira, Maria Paula Marques,Capela, Jorge Manuel Vieira,Lepera, José Salvador
, p. 206 - 210 (2013)
Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC(+)-(S)/(-)-(R) = 1.68). In animals exposed to gasoline, we observed an increase in AUC0-??? for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC(+)-(S)/(-)-(R) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%). Chirality 25:206-210, 2013. 2013 Wiley Periodicals, Inc. Copyright
Fe(OTf)3-catalyzed tandem Meyer-Schuster rearrangement/intermolecular hydroamination of 3-aryl propargyl alcohols for the synthesis of acyclic β-Aminoketones
Tao, Ruiheng,Yin, Yan,Duan, Yongbin,Sun, Yuxing,Sun, Yue,Cheng, Fengkai,Pan, Jinpeng,Lu, Cheng,Wang, Yuan
, p. 1762 - 1768 (2017)
Fe(OTf)3-catalyzed synthesis of acyclic β-aminoketones from 3-aryl propargyl alcohols and nitrogen nucleophiles were investigated. Results showed that propargyl alcohols without bulky groups α to the hydroxyl group underwent the transformation smoothly. Sulphonamides exhibited the higher reactivity than amides as the nitrogen nucleophiles and the transformation of acyclic β-aminoketones were finished in shorter reaction time and higher yields. Finally, racemic fluoxetine was efficiently accessed with the present reaction as the first step. This novel synthesis of acyclic β-aminoketones probable proceeded a Fe(OTf)3-catalyzed Meyer-Schuster rearrangement of 3-aryl propargyl alcohols, followed by a intermolecular hydroamination between nitrogen nucleophiles and α, β-unsaturated ketones.
Absolute configurations and pharmacological activities of the optical isomers of fluoxetine, a selective serotonin-uptake inhibitor
Robertson,Krushinski,Fuller,Leander
, p. 1412 - 1417 (1988)
Fluoxetine is a potent and selective inhibitor of the neuronal serotonin-uptake carrier and is a clinically effective antidepressant. Although fluoxetine is used therapeutically as the racemate, there appears to be a small but demonstrable stereospecificity associated with its interactions with the serotonin-uptake carrier. The goals of this study were to determine the absolute configurations of the enantiomers of fluoxetine and to examine whether the actions of fluoxetine in behavioral tests were enantiospecific. (S)-Fluoxetine was synthesized from (S)-(-)-3-chloro-1-phenylpropanol by sequential reaction with sodium iodide, methylamine, sodium hybride, and 4-fluoro-benzotrifluoride. (S)-Fluoxetine is dextrorotatory (+ 1.60) in methanol, but is levorotatory (- 10.85) in water. Fluoxetine enantiomers were derivatized with (R)-1-(1-naphthyl)ethyl isocyanate, and the resulting ureas were assaysed by 1H NMR or HPLC to determine optical purities of the fluoxetine samples. Both enantiomers antagonized writhing in mice; following sc administration of (R)- and (S)-fluoxetine, ED50 values were 15.3 and 25.7 mg/kg, respectively. Moreover, both enantiomers potentiated a subthreshold analgesic dose (0.25 mg/kg) of morphine, and ED50 values were 3.6 and 5.7 mg/kg, respectively. Following ip administration to mice, the two stereoisomers antagonized p-chloroamphetamine-induced depletion of whole brain serotonin concentrations. ED50 values for (S)- and (R)- fluoxetine were 1.2 and 2.1 mg/kg, respectively. The two enantiomers decreased palatability-induced ingestion following ip administration to rats; (R)- and (S)-fluoxetine reduced saccharin-induced drinking with ED50 values of 6.1 and 4.9 mg/kg, respectively. Thus, in all biochemical and pharmacological studies to date, the eudismic ratio for the fluoxetine enantiomers is near unity.
