Synthesis and resolution of a key building block for epothilones: a comparison of asymmetric synthesis, chemical and enzymatic resolution

Scheid, Günther; Ruijter, Eelco; Konarzycka-Bessler, Monika; Bornscheuer, Uwe T.; Wessjohann, Ludger A.

doi:10.1016/j.tetasy.2004.06.048

Cited by 29 publications

(15 citation statements)

References 31 publications

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“…[31b] During our synthetic studies towards epothilones B and D, [32] we were confronted with the need to introduce an optically pure α-hydroxy ketone functionality. We envisioned that a kinetic resolution of a racemic acyloin acetate with lipases might afford the desired optically pure α-hydroxy ketone.…”

Section: Introductionmentioning

confidence: 99%

A New Route to Protected Acyloins and Their Enzymatic Resolution with Lipases

et al. 2004

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A series of 16 different 3-acyloxy methyl ketones, the acyloin acetates and butyrates (±)-5, was synthesised by a straightforward new method through alkylation of tert-butyl 2-acyloxyacetoacetates 3, followed by chemoselective dealkoxycarbonylation of the tert-butyloxycarbonyl group in the presence of other ester groups. Subsequent hydrolysis of (±)-5 can be achieved with base to give racemic acyloins 6, or with lipase catalysis to afford the corresponding non-racemic acyloins (S)-6. The remaining (R)-acyloin esters 5 can be ra-

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Section: Introductionmentioning

confidence: 99%

A New Route to Protected Acyloins and Their Enzymatic Resolution with Lipases

et al. 2004

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“…The Wessjohann and Bornscheuer group found that in the presence of a lipase from Burkholderia cepacia (Amano PS), the acyloin acetate 47 was hydrolyzed highly enantioselectively with an E value of > 300, leading to the corresponding diol (3 S ,10 R ) -48 in > 99% ee (Scheme 6.17 ) [61] . This is exemplifi ed by the enzymatic hydrolysis of 47 , which represents a key building block of epothilones.…”

Section: Ester Hydrolysismentioning

confidence: 99%

Enzyme‐Catalyzed Asymmetric Synthesis

Gröger

2010

Catalytic Asymmetric Synthesis

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INTRODUCTIONBiocatalysis has been recognized over the past decades as a highly valuable tool for organic chemists to prepare enantiomerically pure molecules, so -called chiral building blocks, in a highly effi cient way. Besides a multitude of academic work, it is noteworthy that enzyme catalysis belongs to the standard repertoire in industry when facing challenging enantioselective synthetic routes. A broad range of biocatalytic methods is already in use in particular for large -scale manufacture of drug intermediates [1] .The research in the fi eld of enzyme catalysis has already been comprehensively reviewed some years ago [2] . Thus, the focus of the current review is on a selection of (particularly recently developed) enantioselective enzymatic reactions, which turned out to be highly useful and applicable in organic synthesis, fulfi lling criteria such as high productivity, substrate concentrations, conversions, and enantioselectivities. The presented methods are an interesting complementary tool to existing " classic organic " or " chemocatalytic asymmetric " methodologies. Among biocatalytic reactions, both resolution of racemates and asymmetric synthesis starting from prochiral substrates are attractive routes already applied, in part, in industry. A third type of biotechnological approach, which is not a subject of this review, are fermentation processes. A graphical summary of these three types of so -called " white biotechnology " methodologies is given in Scheme 6.1 .Hydrolases are the enzyme class most commonly applied as biocatalysts in organic chemistry. This is mainly due to the accessibility of these enzymes (used, e.g., in the textile and detergents industry), their suitability for transformations in organic media Catalytic Asymmetric Synthesis, Third Edition, Edited by Iwao Ojima 269 270 ENZYME-CATALYZED ASYMMETRIC SYNTHESIS (in particular when using lipases), and the lack of a need for cofactors. However, in recent years, we have also seen an increasing tendency to apply redox enzymes in organic syntheses as well as lyases in C -C bond formations and transferases. Isomerases also turned out to be very useful in particular in combination with hydrolases for dynamic kinetic resolutions. Thus, a broad range of biotransformations is available for organic chemists. A challenge, however, is the use of ATP cofactor -dependent enzymes, which contribute to only a negligible number of typical organic biotransformations (e.g., due to the high price of ATP).The fi eld of biocatalysis benefi ted signifi cantly from the tremendous progress in molecular biology. Highly effi cient methods for screening and optimization of biocatalysts (by, e.g., directed evolution in the latter case) have been developed, which allows access to tailor -made enzymes. Furthermore, the design of recombinant microorganisms gives access to highly productive whole -cell catalysts, which contain only the desired enzymes in large amount, thus signifi cantly reducing the required biomass for biotransformations compared with the use of...

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“…21 Hydrolysis of this acetate proceeded smoothly to the acyloin 12 , 23 but then our efforts to bring about oxidative cleavage to the carboxylic acid went unrewarded. In contrast, reduction of compound 11 proceeded smoothly upon treatment with LiAlH 4 to give the diol 13 as a mixture of stereoisomers, and oxidative cleavage by treatment with sodium periodate on silica gel gave the expected aldehyde 14 in nearly quantitative yield.…”

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confidence: 99%

“…For our purposes, the β-keto acetate derivative 10 was prepared from neryl bromide and tert -butyl 2-acetoxyacetoacetate according to the known procedure, and subsequent decarboxylation upon treatment with TsOH gave racemic acetate 11 (Scheme ). Hydrolysis of this acetate proceeded smoothly to the acyloin 12 , but then our efforts to bring about oxidative cleavage to the carboxylic acid went unrewarded. In contrast, reduction of compound 11 proceeded smoothly upon treatment with LiAlH 4 to give the diol 13 as a mixture of stereoisomers, and oxidative cleavage by treatment with sodium periodate on silica gel gave the expected aldehyde 14 in nearly quantitative yield.…”

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confidence: 99%