A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine

Hilborn, J. W.; Lu, Zexi; Jurgens, Alex R.; Fang, Q. Kevin; Byers, Paul D.; Wald, Stephen A.; Senanayake, Chris H.

doi:10.1016/s0040-4039(01)01877-9

Cited by 105 publications

(51 citation statements)

References 21 publications

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“…Subsequent O-arylation of 4-chlorotrifluoromethylbenzene was accomplished using sodium hydride in DMSO (norfluoxetine) (Mitchell and Koening, 1995) or in dimethylacetamide (fluoxetine) (Kamal et al, 2002). The tartrate salts of norfluoxetine enantiomers were prepared by the method described previously (Hilborn et al, 2001).…”

Section: Chemical Syntheses Of Primary Amine and Secondary Hydroxylammentioning

confidence: 99%

Sequential Metabolism of Secondary Alkyl Amines to Metabolic-Intermediate Complexes: Opposing Roles for the Secondary Hydroxylamine and Primary Amine Metabolites of Desipramine, (S)-Fluoxetine, and N-Desmethyldiltiazem

Hanson¹,

VandenBrink²,

Babu³

et al. 2010

Drug Metab Dispos

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Section: Chemical Syntheses Of Primary Amine and Secondary Hydroxylammentioning

confidence: 99%

Sequential Metabolism of Secondary Alkyl Amines to Metabolic-Intermediate Complexes: Opposing Roles for the Secondary Hydroxylamine and Primary Amine Metabolites of Desipramine, (S)-Fluoxetine, and N-Desmethyldiltiazem

Hanson¹,

VandenBrink²,

Babu³

et al. 2010

Drug Metab Dispos

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“…Within this class, alcohol dehydrogenases (E.C.1.1.1.1, also known as keto-reductase) represent an important group of biocatalysts due to their ability to stereospecifically reduce prochiral carbonyl compounds. Alcohol dehydrogenases (ADH) can be used efficiently in the synthesis of optically active alcohols, which are key building blocks for the fine chemicals industry [1,2].…”

Section: Introductionmentioning

confidence: 99%

Cloning, Expression, and Characterization of a Novel (S)-Specific Alcohol Dehydrogenase from Lactobacillus kefir

QiLei

Zhao

et al. 2008

Appl Biochem Biotechnol

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A gene encoding a novel (S)-specific NADH-dependent alcohol dehydrogenase (LK-ADH) was isolated from the genomic DNA of Lactobacillus kefir DSM 20587 by thermal asymmetric interlaced-polymerase chain reaction. The nucleotide sequence of (S)-LK-ADH gene (adhS) was determined, which consists of an open reading frame of 1,044 bp, coding for 347 amino acids with a molecular mass of 37.065 kDa. After a BLAST similarity search in GenBank database, the amino acid sequence of (S)-LK-ADH showed some homologies to several zinc containing medium-chain alcohol dehydrogenases. This novel gene was deposited into GenBank with the accession number of EU877965. adhS gene was subcloned into plasmid pET-28a(+), and recombinant (S)-LK-ADH was successfully expressed in E. coli BL21(DE3) by isopropyl-beta-D-1-thiogalactopyranoside induction. Purified enzyme showed a high enantioselectivity in the reduction of acetophenone to (S)-phenylethanol with an ee value of 99.4%. The substrate specificity and cofactor preference of recombinant (S)-LK-ADH were also tested.

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“…Merck used the same catalyst to reduce bistrifluoro-acetophenone on kilogram scale but, compared to the results for the (transfer) hydrogenation processes described above, the TON (20-50) and TOF (*20 h -1 ) were much lower [117,120]. Sepracor also developed this technology for an aryl-c-keto ester with respectable ee-values but, again, low activity [121], while Merck reported a pilot process for the reduction of a more complex intermediate using the aminoindanol ligand N^O (see Fig. 37.31) [122].…”

Section: Aromatic Ketonesmentioning

confidence: 99%

Industrial Applications

Blaser¹,

Spindler²,

Thommen³

2006

The Handbook of Homogeneous Hydrogenation

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While hydrogenation is without doubt the most important catalytic methodology for the manufacture of fine chemicals, until now most reactions have been carried out with heterogeneous catalysts. Heterogeneous hydrogenation catalysts have an exceptionally broad applicability for the chemo-and diastereoselective reduction of various functional groups, are convenient to handle, and catalyst separation is usually straightforward [1]. Homogeneous catalysts have found application for a number of special selectivity problems, the most important of which is enantioselective hydrogenation. While this will be the dominant topic of this chapter, a few scattered reports have been made where achiral complexes such as the Wilkinson catalyst, RhCl(Ph 3 P) 3 , or Ru-phosphine complexes have been applied on an industrial scale. In this regard, we will mention three examples [2]: (i) the chemoselective hydrogenation of a,b-unsaturated aldehydes; (ii) the diastereoselective hydrogenation of a tetracycline antibiotic; and (iii) the chemoselective hydrogenation of avermectin derivatives.As already mentioned, the most important industrial application of homogeneous hydrogenation catalysts is for the enantioselective synthesis of chiral compounds. Today, not only pharmaceuticals and vitamins [3], agrochemicals [4], flavors and fragrances [5] but also functional materials [6,7] are increasingly produced as enantiomerically pure compounds. The reason for this development is the often superior performance of the pure enantiomers and/or that regulations demand the evaluation of both enantiomers of a biologically active compound before its approval. This trend has made the economical enantioselective synthesis of chiral performance chemicals a very important topic.Industrial interest in the application of enantioselective catalysts began in earnest during the mid-1960s when the first reports of successful enantioselective transformations with homogeneous metal complexes were published. Within a surprisingly short period, production processes for two small-scale products, l-dopa (hydrogenation) and cilostatin (cyclopropanation) were developed and implemented by 1279The Handbook of Homogeneous Hydrogenation. Edited by J. G. de Vries and C. J. Elsevier

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A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine

Cited by 105 publications

References 21 publications

Sequential Metabolism of Secondary Alkyl Amines to Metabolic-Intermediate Complexes: Opposing Roles for the Secondary Hydroxylamine and Primary Amine Metabolites of Desipramine, (S)-Fluoxetine, and N-Desmethyldiltiazem

Sequential Metabolism of Secondary Alkyl Amines to Metabolic-Intermediate Complexes: Opposing Roles for the Secondary Hydroxylamine and Primary Amine Metabolites of Desipramine, (S)-Fluoxetine, and N-Desmethyldiltiazem

Cloning, Expression, and Characterization of a Novel (S)-Specific Alcohol Dehydrogenase from Lactobacillus kefir

Industrial Applications

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