Enantioselective Synthesis of α-Hydroxy Ketones via Benzaldehyde Lyase-Catalyzed C−C Bond Formation Reaction

Demir, Ayhan S.; Şeşenoğlu, Özge; Eren, Elif; Hosrik, Birsu; Pohl, Martina; Janzen, Elena; Kolter, Doris; Feldmann, Ralf; Dünkelmann, Pascal; Müller, Michael

doi:10.1002/1615-4169(200201)344:1<96::aid-adsc96>3.0.co;2-z

Cited by 164 publications

(102 citation statements)

References 15 publications

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“…Furthermore, using related chiral triazolium A 20 , Gravel effected the reaction in a promising 40% ee. Aside from enzymatic catalysts, 62 this is one of two examples of an enantioselective intermolecular cross-benzoin reaction between two aldehydes (Scheme 19). The other example was reported by Yang but used a large excess of the aliphatic aldehyde (10 equiv, delivering cross-benzoin adduct in 41% yield and 60% ee).…”

Section: Umpolung Acyl-anion Catalysismentioning

confidence: 99%

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

et al. 2015

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Section: Umpolung Acyl-anion Catalysismentioning

confidence: 99%

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

et al. 2015

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“…4.1.2.38) have been intensively studied with respect to their carboligation activity, offering an easy access to chiral 2-hydroxy ketones from aldehydes. [1][2][3][4][5][6][7][8] In order to enlarge the range of accessible 2-hydroxy ketones, we studied the carboligase properties of a recently described branchedchain keto acid decarboxylase (E.C. 4.1.1.72).…”

Section: Introductionmentioning

confidence: 99%

Branched‐Chain Keto Acid Decarboxylase from Lactococcus lactis (KdcA), a Valuable Thiamine Diphosphate‐Dependent Enzyme for Asymmetric CC Bond Formation

et al. 2007

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The thiamine diphosphate-dependent, branched-chain 2-keto acid decarboxylase from Lactococcus lactis sup. cremoris B1157 (KdcA) is a new valuable enzyme for the synthesis of chiral 2-hydroxy ketones. The gene was cloned and the enzyme was expressed as an N-terminal hexahistidine fusion protein in Escherichia coli. It has a broad substrate range for the decarboxylation reaction including linear and branched-chain aliphatic and aromatic keto acids as well as phenyl pyruvate and indole-3pyruvate. The dimeric structure of recombinant KdcA is in contrast to the tetrameric structure of other 2-keto acid decarboxylases. The enzyme is stable between pH 5 and 7 with a pH optimum of pH 6-7 for the decarboxylation reaction. While KdcA is sufficiently stable up to 40 8C it rapidly looses activity at higher temperatures. In this work the carboligase activity of KdcA is demonstrated for the first time. The enzyme shows an exceptionally broad substrate range and, most strikingly, it catalyzes the carboligation of different aromatic aldehydes as well as CH-acidic aldehydes such as phenylacetaldehyde and indole-3-acetaldehyde with aliphatic aldehydes such as acetaldehyde, propanal, and cyclopropanecarbaldehyde, yielding chiral 2-hydroxy ketones in high enantiomeric excess. Noteworthy, the donor-acceptor selectivity is strongly influenced by the nature of the respective substrate combination.

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“…1). If incubated with an excess of benzaldehyde, BAL also catalyses the formation of the industrial pharmaceutical intermediate (R)-benzoin by enantioselective carbon-carbon bond ligation (Demir et al, 2002). A range of other aldehyde substrates for BAL have recently been identified (Sanchez-Gonzalez & Rosazza, 2003;Demir et al, 2003) and there is an increasing number of reports of the optimization of its activity for possible application of the enzyme in industrial processes (Stilger et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Structure of the ThDP-dependent enzyme benzaldehyde lyase refined to 1.65 Å resolution

et al. 2007

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Benzaldehyde lyase (BAL; EC 4.1.2.38) is a thiamine diphosphate (ThDP) dependent enzyme that catalyses the enantioselective carboligation of two molecules of benzaldehyde to form (R)-benzoin. BAL has hence aroused interest for its potential in the industrial synthesis of optically active benzoins and derivatives. The structure of BAL was previously solved to a resolution of 2.6 Å using MAD experiments on a selenomethionine derivative [Mosbacher et al. (2005), FEBS J. 272, 6067-6076]. In this communication of parallel studies, BAL was crystallized in an alternative space group (P2 1 2 1 2 1) and its structure refined to a resolution of 1.65 Å , allowing detailed observation of the water structure, active-site interactions with ThDP and also the electron density for the co-solvent 2-methyl-2,4-pentanediol (MPD) at hydrophobic patches of the enzyme surface.

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Enantioselective Synthesis of α-Hydroxy Ketones via Benzaldehyde Lyase-Catalyzed C−C Bond Formation Reaction

Cited by 164 publications

References 15 publications

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

Branched‐Chain Keto Acid Decarboxylase from Lactococcus lactis (KdcA), a Valuable Thiamine Diphosphate‐Dependent Enzyme for Asymmetric CC Bond Formation

Structure of the ThDP-dependent enzyme benzaldehyde lyase refined to 1.65 Å resolution

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