Combining Lipase-Catalyzed Enantiomer-Selective Acylation with Fluorous Phase Labeling:  A New Method for the Resolution of Racemic Alcohols

Hungerhoff, Benno; Sonnenschein, Helmut; Theil, Fritz

doi:10.1021/jo010767p

Cited by 42 publications

(24 citation statements)

References 27 publications

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“…[81] Alternatively, lipase-catalyzed saponification of a racemic fluorinated ester can be conducted under triphasic conditions in a U-tube such that the product alcohol collects in one methanolic phase. [82] The unreacted ester remains in the fluorinated solvent phase during lipase hydrolysis, and is then saponified by contact with aqueous hydroxide in a second methanol layer.…”

Section: Methodsmentioning

confidence: 99%

Efficiency in Nonenzymatic Kinetic Resolution

2005

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The Walden memorial at the Technical University in Riga is pictured in the frontispiece to mark the recent centennial of the Walden inversion. This is a rare public monument to key events from the first era of exploration in stereocontrolled synthesis, and may be the only such monument to use the language of organic chemistry expressed at the molecular level. The reaction of racemic substrates with chiral nucleophiles is one of many methods currently known to achieve kinetic resolution, a phenomenon that ranks as the oldest and most general approach for the synthesis of highly enantioenriched substances. The first nonenzymatic kinetic resolutions as well as the original forms of the Walden inversion were studied in the 1890s. All of these investigations were conducted within the first generation following the demonstration that carbon is tetrahedral, and provided abundant evidence that the principles and importance of enantiocontrolled syntheses were understood. However, a reliable, rapid technique to quantify results and guide the optimization process was still lacking. Many decades passed before this problem was solved by the advent of HPLC and GLPC assays on chiral supports, which stimulated explosive growth in the synthesis of nonracemic substances by kinetic resolution. The Walden monument is accessible to passers-by for hands-on inspection as well as for contemplation and learning. In a similar way, kinetic resolution is experimentally accessible and can be thought-provoking at several levels. We follow the story of kinetic resolution from the early discoveries through fascinating historical milestones and conceptual developments, and close with a focus on modern techniques that maximize efficiency.

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Section: Methodsmentioning

confidence: 99%

Efficiency in Nonenzymatic Kinetic Resolution

2005

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“…[18] As shown in Scheme 3 (top), we could prepare this bromide directly from the alcohol using CBr 4 and PPh 3 . [19] Interestingly, H 2 SO 4 and aqueous HBr [20] gave only modest conversions, even at temperatures of > 100 8C in sealed vessels.…”

Section: H T U N G T R E N N U N G (Ch 2 ) 3 ]A C H T U N G T R E Nmentioning

confidence: 99%

Syntheses and Properties of Fluorous Quaternary Phosphonium Salts that Bear Four Ponytails; New Candidates for Phase Transfer Catalysts and Ionic Liquids

et al. 2006

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“…Novel application of fluorous solvents in product isolation following biocatalysis An interesting application of solvents for biocatalysis was developed in 2002 by Theil et al [165][166][167] Initially lipase-mediated kinetic resolution of a range of alcohols with fluorous esters was performed and repeated washing with the fluorous solvent removed the transformed ester in high enantiopurity with the untransformed alcohol remaining in the organic phase also in excellent enantiopurity. 165 This methodology was adapted to lipase-mediated hydrolysis of highly fluorinated esters with similar results. 166,167 Source phase Combination of the kinetic resolution by enzymatic deacylation with fluorous triphasic reaction and subsequent separation yielded the enantiomeric alcohols in excellent enantiopurities and good yields ( Figure 5).…”

Section: Anionmentioning

confidence: 99%

Recent trends in whole cell and isolated enzymes in enantioselective synthesis

Milner¹,

Maguire²

2012

Arkivoc

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Modern synthetic organic chemistry has experienced an enormous growth in biocatalytic methodologies; enzymatic transformations and whole cell bioconversions have become generally accepted synthetic tools for asymmetric synthesis. This review details an overview of the latest achievements in biocatalytic methodologies for the synthesis of enantiopure compounds with a particular focus on chemoenzymatic synthesis in non-aqueous media, immobilisation technology and dynamic kinetic resolution. Furthermore, recent advances in ketoreductase technology and their applications are also presented.Keywords: Biocatalysis, kinetic and dynamic kinetic resolution, Baker's yeast, ketoreductases General IntroductionAsymmetric synthesis is the preferential formation of one stereoisomer of a chiral target compound to another; when scientists at GlaxoSmithKline, AstraZeneca and Pfizer 1 examined 128 syntheses from their companies, they found as many as half of the drug compounds made by their process research and development groups are not only chiral but also contain an average of two chiral centres each. 2In 2006 just 25 % were derived from the chiral pool and over 50 % employed chiral technologies. 1In order to meet regulatory requirements enantiomeric purities of 99.5 % were deemed necessary by the FDA. 3 This is one of the biggest challenges which face chemists today, primarily due to the recognition of the fact that different enantiomers of the same compound can interact differently in biological systems. As a consequence, the production of single enantiomers instead of racemic mixtures has become an important process in the pharmaceutical and agrochemical industry. Several routes can lead to the desired enantiomer including transition metal-, [4][5][6] organo-5,7-10 and bio-catalysis [11][12][13][14][15] and these have been thoroughly reviewed in the literature. 16,17 2. Biocatalysis IntroductionBiocatalysis involves the use of enzymes or whole cells (containing the desired enzyme or enzyme system) as catalysts for chemical reactions. A timeline of historic events in biocatalysis and biotechnology is outlined in Table 1. [18][19][20] Reviews and Accounts Novel methodologies for discovering industrial enzymes based on genomic sequencing and phage display (discussed further in Section 1.3), 21,22 as well as highly effective optimisation tools based on chemical, physical and molecular biology approaches, 23 have improved the access to biocatalysts, increased their stability, and radically broadened their specificity. 24This greater availability of catalysts with superior qualities including the use of new bioengineering tools contributed significantly to the development of new industrial processes. Biocatalytic methodologies for organic synthesis were outlined by Woodley et al. in three categories: established, emerging and expanding chemistries as depicted in Figure 1. 25 Enzyme classesBy the late 1950s it had become evident that the nomenclature of enzymes without any guiding authority, in a period when the...

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Combining Lipase-Catalyzed Enantiomer-Selective Acylation with Fluorous Phase Labeling: A New Method for the Resolution of Racemic Alcohols

Cited by 42 publications

References 27 publications

Efficiency in Nonenzymatic Kinetic Resolution

Efficiency in Nonenzymatic Kinetic Resolution

Syntheses and Properties of Fluorous Quaternary Phosphonium Salts that Bear Four Ponytails; New Candidates for Phase Transfer Catalysts and Ionic Liquids

Recent trends in whole cell and isolated enzymes in enantioselective synthesis

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