Enantioselective C–C bond synthesis catalysed by enzymes
ABSTRACT The enantioselective synthesis of C-C bonds is often the pivotal step of a synthesis. Nature has made a variety of versatile enzymes available that catalyse this type of reaction very selectively under mild conditions. Cyanohydrins, acyloins (alpha-hydroxy ketones), alpha-hydroxy acids and aldols (beta-hydroxy ketones) are very efficiently synthesised enantioselectively with the aid of C-C bond forming enzymes, which we discuss in this tutorial review. In the case of the alpha-hydroxy acids the applications of nitrilases in a synthetic dkr even allows a disconnection that has no enantioselective chemical equivalent.
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ABSTRACT: Benzoylformate decarboxylase (BFD, EC 220.127.116.11) is a homotetrameric thiamine diphosphate (ThDP)-dependent enzyme which catalyzes the synthesis of chiral 2-hydroxyketones accepting a broad range of aldehydes as substrates. In this study the synthesis of 2-hydroxypropiophenone (2-HPP) from benzaldehyde and acetaldehyde was catalyzed by three BFD variants namely BFD F464I, BFD A460I and BFD A460I-F464I. This paper reports the effect of hydrostatic pressure up to 290 MPa when the reactions were carried out at different benzaldehyde concentrations (5-40 mM) as well as at different pH values (7.0-8.5). Acetaldehyde concentration was fixed at 400 mM in all biotransformations. Reactions performed at high benzaldehyde concentrations and at high hydrostatic pressures showed an increase in (R)-2-HPP formation catalyzed by all BFD variants. For BFD A460I-F464I we observed an increase in the ee of (R)-2-HPP up to 80%, whereas at atmospheric conditions this variant synthesizes (R)-2-HPP with an ee of only 50%. Alkaline conditions (up to pH 8.5) and high hydrostatic pressures resulted in an increase of (R)-2-HPP synthesis, especially in the case of BFD A460I and BFD F464I.Journal of Biotechnology 02/2011; 152(3):87-92. DOI:10.1016/j.jbiotec.2011.01.020 · 2.88 Impact Factor
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ABSTRACT: Several proteases, especially pepsin, were observed to directly catalyze asymmetric aldol reactions. Pepsin, which displays well-documented proteolytic activity under acidic conditions, exhibited distinct catalytic activity in a crossed aldol reaction between acetone and 4-nitrobenzaldehyde with high yield and moderate enantioselectivity. Fluorescence experiments indicated that under neutral pH conditions, pepsin maintains its native conformation and that the natural structure plays an important role in biocatalytic promiscuity. Moreover, no significant loss of enantioselectivity was found even after four cycles of catalyst recycling, showing the high stability of pepsin under the selected aqueous reaction conditions. This case of biocatalytic promiscuity not only expands the application of proteases to new chemical transformations, but also could be developed into a potentially valuable method for green organic synthesis.Journal of Biotechnology 10/2010; 150(4):539-45. DOI:10.1016/j.jbiotec.2010.10.004 · 2.88 Impact Factor
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ABSTRACT: Aldolases are a specific group of lyases that catalyze the reversible stereoselective addition of a donor compound (nucleophile) onto an acceptor compound (electrophile). Whereas most aldolases are specific for their donor compound in the aldolization reaction, they often tolerate a wide range of aldehydes as acceptor compounds. C-C bonding by aldolases creates stereocenters in the resulting aldol products. This makes aldolases interesting tools for asymmetric syntheses of rare sugars or sugar-derived compounds as iminocyclitols, statins, epothilones, and sialic acids. Besides the well-known fructose 1,6-bisphosphate aldolase, other aldolases of microbial origin have attracted the interest of synthetic bio-organic chemists in recent years. These are either other dihydroxyacetone phosphate aldolases or aldolases depending on pyruvate/phosphoenolpyruvate, glycine, or acetaldehyde as donor substrate. Recently, an aldolase that accepts dihydroxyacetone or hydroxyacetone as a donor was described. A further enlargement of the arsenal of available chemoenzymatic tools can be achieved through screening for novel aldolase activities and directed evolution of existing aldolases to alter their substrate- or stereospecifities. We give an update of work on aldolases, with an emphasis on microbial aldolases.Applied Microbiology and Biotechnology 08/2006; 71(3):253-64. DOI:10.1007/s00253-006-0422-6 · 3.81 Impact Factor