A short enantioselective synthesis of the antiepileptic agent, levetiracetam based on proline-catalyzed asymmetric α-aminooxylation

Kotkar, Shriram P.; Sudalai, Arumugam

doi:10.1016/j.tetlet.2006.07.061

Cited by 51 publications

(16 citation statements)

References 23 publications

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“…Other target molecules which had been successfully synthesized using proline catalyzed α-aminoxylation as one of the key steps include halipeptin A [ 104 ], (+)- exo - and (–)- endo -brevicomins [ 105 ], linezolid and eperezolid [ 106 ], levetiracetam [ 107 ], ( S , S )-ethambutol [ 108 ], (+)-harzialactone A and ( R )-(+)-4-hexanolide [ 109 ], ( R )-seleginine [ 110 ], ( S )-propanolol and ( S )-naftopidil [ 111 ], (+)-disparlure and its trans -isomer [ 112 ], (-)-anisomycin [ 59 ] and (1 R ,3 S )-thysanone, a HRV 3C-protease inhibitor [ 113 ].…”

Section: α-Aminoxylation Reactionsmentioning

confidence: 99%

Organocatalyzed Asymmetric α-Oxidation, α-Aminoxylation and α-Amination of Carbonyl Compounds

2010

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Organocatalytic asymmetric α-oxidation and amination reactions of carbonyl compounds are highly useful synthetic methodologies, especially in generating chiral building blocks that previously have not been easily accessible by traditional methods. The concept is relatively new and therefore the list of new catalysts, oxidizing and aminating reagents, as well as new substrates, are expanding at an amazing rate. The scope of this review includes new reactions and catalysts, mechanistic aspects and synthetic applications of α-oxidation, hydroxylation, aminoxylation, amination, hydrazination, hydroxyamination and related α-heteroatom functionalization of aldehydes, ketones and related active methylene compounds published during 2005–2009.

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Section: α-Aminoxylation Reactionsmentioning

confidence: 99%

Organocatalyzed Asymmetric α-Oxidation, α-Aminoxylation and α-Amination of Carbonyl Compounds

2010

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“…To date, several methodologies have been applied to produce LEV for the increasing demand of AEDs, which involve resolution processes and asymmetric syntheses [6][7][8]. However, obtaining enantiomerically pure LEV through conventional chemical synthetic protocols is costly and laborious.…”

Section: Introductionmentioning

confidence: 99%

Purification and Immobilization of a Novel Enantioselective Lipase from Tsukamurella tyrosinosolvents for Efficient Resolution of Ethyl 2-(2-oxopyrrolidin-1-yl) Butyrate

Huang

Ren

et al. 2016

Appl Biochem Biotechnol

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A highly enantioselective lipase from Tsukamurella tyrosinosolvents E105 was purified via ultrasonic extraction, precipitation, and chromatographic steps. The enzyme was purified about 38-fold with the recovery yield of 9 % and was confirmed as a dimer protein consisting of two identical subunits with a molecular mass of 24 kDa. The purified lipase was used to catalyze resolution of racemic ethyl 2-(2-oxopyrrolidin-1-yl) butyrate to (S)-2-(2-oxopyrrolidin-1-yl) butyric acid. The maximum activity of such lipase was obtained at pH 7.5, 35 °C, and the highest relative activity (156.80 %) was observed in the presence of 0.5 mM Co. Subsequently, the lipase was encapsulated within a mixture of 3 % sodium alginate and 0.8 % carrageenan, and then cross-linked with 0.6 % glutaraldehyde to enhance its biocatalytic capability and stability. Comparing with 36.9 % product yield and 97.5 % product ee of free lipase, the highest product yield of 46.3 % and ee of 98.5 % for immobilized lipase were achieved with the presence of 20 mM substrate. In addition, the reusability of immobilized lipase was also investigated, which could maintain 63.7 % of its initial conversion yield after seven repeated batch reactions. Thus, the evaluated enantioselective lipase in this work has a good potential for further industrial application.

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“…Reported methods for the synthesis of levetiracetam typically involve chiral pool approaches starting from relevant enantiopure -amino acids [5][6][7][8], resolution of etiracetam or advanced racemic intermediates [5][6][7][8][9][10], asymmetric hydrogenation over Rh (I) or Ru(II) complexes [11,12], and deracemization of 2-bromobutyric acid using N-phenyl pantolactam as a chiral auxiliary [13], proline catalyzed asymmetric -aminooxylation [14].…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Synthesis of Antiepileptic Agent, (−)‐Levetiracetam, through Evans Asymmetric Strategy

Babu

Reddy

Mukkanti

et al. 2012

Journal of Chemistry

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A practical and efficient enantioselective synthesis of antiepileptic drug, (−)-Levetiracetam, has been described in five steps (33.0% overall yield) and high optical purity (99.0%ee), using Evans asymmetric strategy forα-alkylation of carbonyl functionality as the key step. The simplicity of the experimental procedures and high stereochemical outcome make this method synthetically attractive for preparing the target compound on multigram scales.

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A short enantioselective synthesis of the antiepileptic agent, levetiracetam based on proline-catalyzed asymmetric α-aminooxylation

Cited by 51 publications

References 23 publications

Organocatalyzed Asymmetric α-Oxidation, α-Aminoxylation and α-Amination of Carbonyl Compounds

Organocatalyzed Asymmetric α-Oxidation, α-Aminoxylation and α-Amination of Carbonyl Compounds

Purification and Immobilization of a Novel Enantioselective Lipase from Tsukamurella tyrosinosolvents for Efficient Resolution of Ethyl 2-(2-oxopyrrolidin-1-yl) Butyrate

Enantioselective Synthesis of Antiepileptic Agent, (−)‐Levetiracetam, through Evans Asymmetric Strategy

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