Hydroxynitrile lyases cyanohydrin

Hydroxynitrile lyase Cyanohydrin formation R- and S-enzymes Few enzymes State of the art, commercial enzymes ... 

Hydroxynitrile lyase can be used for the decomposition of cyanohydrins with some level of enantioselectivity. " ... 

Griengl reported the first example of hydroxynitrile lyase-catalyzed cyanohydrin formation in a mixed solvent system of [bmim][BF4] and buffer (pH 3.7) (1 1) (Fig. 19). In the reaction, a mixed solvent system was essential, but excellent results were obtained. 

Figure 19 Enantioselective cyanohydrin formation using hydroxynitrile lyase in...

The hydroxynitrile lyase (HNL)-catalyzed addition of HCN to aldehydes is the most important synthesis of non-racemic cyanohydrins. Since now not only (f )-PaHNL from almonds is available in unlimited amounts, but the recombinant (S)-HNLs from cassava (MeHNL) and rubber tree (HbHNL) are also available in giga units, the large-scale productions of non-racemic cyanohydrins have become possible. The synthetic potential of chiral cyanohydrins for the stereoselective preparation of biologically active compounds has been developed during the last 15 years. 

Hydroxynitrile lyases (HNLs or oxynitrilases) catalyze C—C bond-forming reactions between an aldehyde or ketone and cyanide to form enantiopure cyanohydrins (Figure 1.15), which are versatile building blocks for the chiral synthesis of amino acids, hydroxy ketones, hydroxy acids, amines and so on [68], Screening of natural sources has led to the discovery of both... 

Forster, S., Roos, J., Effenberger, F. et al. (1996) The first recombinant hydroxynitrile lyase and its application in the synthesis of (S)-cyanohydrins. Angewandte Chemie (International Edition in English), 35, 457 459. 

Gaisberger, R.P., Fechter, M.H. and Griengl, H. (2004) The first hydroxynitrile lyase catalysed cyanohydrin formation in ionic liquids. Tetrahedron Asymmetry, 15, 2959-2963. 

Costes, D., Wehtje, E. and Adlercreutz, P. (2001) Cross-linked crystals of hydroxynitrile lyase as catalyst for the synthesis of optically active cyanohydrins. Journal of Molecular Catalysis B-Enzymatic, 11, 607-612. 

Rhodococcus erythropolis NCIMB 11540 has been employed as biocatalyst for the conversion of (R)- or (.S )-cyanohydrins to the corresponding (R)- or (S)-a-hydroxycarboxylic acids with an optical purity of up to >99% enatiomeric excess (ee) [27-29] the chiral cyanohydrins can separately be produced using hydroxynitrile lyase from Hevea braziliensis or from Prunus anygdalis [30]. Using the combined NHase-amidase enzyme system of the Rhodococcus erythropolis NCIMB 11 540, the chiral cyanohydrins were first hydrolyzed to the... 

Roberge, C., Eleitz, E., Pollard, D. and Devine, P., Asymmetric synthesis of cyanohydrin derived from pyridine aldehyde with cross-linked aggregates of hydroxynitrile lyases. Tetrahedron Lett., 2007, 48, 1473-1477. 

The hydroxynitrile lyase (HNL)-catalysed cyanohydrin reaction is a useful method to synthesize enantiopure a-hydroxy nitriles and the corresponding a-hydroxy acids. However, small ketones, such as 2-butanone, are converted with low selectivities, due to the poor discrimination between methyl and ethyl. ... 

Selective Cyanohydrin Formation from Aromatic Ketones Using Hydroxynitrile Lyases... 

The production of optically active cyanohydrins, with nitrile and alcohol functional groups that can each be readily derivatized, is an increasingly significant organic synthesis method. Hydroxynitrile lyase (HNL) enzymes have been shown to be very effective biocatalysts for the formation of these compounds from a variety of aldehyde and aliphatic ketone starting materials.Recent work has also expanded the application of HNLs to the asymmetric production of cyanohydrins from aromatic ketones. In particular, commercially available preparations of these enzymes have been utilized for high ee (5)-cyanohydrin synthesis from phenylacetones with a variety of different aromatic substitutions (Figure 8.1). 

Hydroxynitrile-lyase-catalysed Synthesis of Enantiopure (5)-Acetophenone Cyanohydrins... 

Chiral cyanohydrins are versatile intermediates in the synthesis of a-hydroxy acids, /3-amino alcohols, amino nitriles, a-hydroxy ketones and aziridines. For the synthesis of enantiopure cyanohydrins, the use of hydroxynitrile lyases is currently the most effective approach.Application of an organic-solvent-free system allows thermodynamically hindered substrates to be converted with moderate to excellent yields. With the use of the highly selective hydroxynitrile lyase from Manihot esculenta, the syntheses of several acetophenone cyanohydrins with excellent enantioselectivities were developed (Figure 8.2). (5)-Acetophenone cyanohydrin was synthesized on a preparative scale. ... 

A New (/ )-Hydroxynitrile Lyase from Prunus mume for Asymmetric Synthesis of Cyanohydrins... 

A new hydroxynitrile lyase (HNL) was isolated from the seed of Japanese apricot Prunus mume). It accepts benzaldehyde and a large number of unnatural substrates for the addition of HCN to produce the corresponding (7 )-cyanohydrins in excellent optical and chemical yields. A new high-performance liquid chromatography (HPLC)-based enantioselective assay technique was developed for the enzyme, which promotes the addition of KCN to benzaldehyde in a buffered solution (pH 4.0). Asymmetric synthesis of (7 )-cyanohydrins by a new HNL is described (Figure 8.4). ... 

We have found a new (/ )-hydroxynitrile lyase from Japanese apricot (P. mume). The new enzyme accepts a broad array of substrates, ranging from aromatic, heteroaromatic, bicyclic to aliphatic carbonyl compounds, and yields the corresponding cyanohydrins with excellent enantioselection. 

Another notable new advance is the development of hydroxynitrile lyases for the synthesis of enantiomerically active aromatic and aliphatic cyanohydrins. For instance, an S-specific hydroxynitrile lyase has been obtained from Hevea brasiliensis and the resulting fS)-cyanohydrin can be used to obtain both hydroxy acids and aminoalcohols. 

K. Trummler, H. Wajant, Molecular cloning of acetone cyanohydrin lyase from flax Linum usitatissimum). Definition of a novel class of hydroxynitrile lyases./. Biol. Chem. 1997, 272, 4770-4774. 

Scheme 7.23 Synthesis of chiral cyanohydrins from 3-pyridinecarboxyaldehyde in organic solvent using commercially available CLEA particles of hydroxynitrile lyases.

The commercially available CLEA particles of hydroxynitrile lyases (HNLs) from cassava and almond were used to produce both enantiomers. The use of dichloromethane, free hydrogen cyanide, and low temperatures was important for improving the cyanohydrin stereoselectivity and suppressing the background reaction. The aggregate particles were easily separated from the reaction by filtration followed by washing, and up to ten times reuse was demonstrated. 

In the last decades, cyanohydrins have become versatile chiral building blocks, not only for laboratory synthesis, but also for a range of pharmaceuticals and agrochemicals. Several methods for the enantioselective preparation of these compounds have been published [1, 2]. The most important synthetic approaches are catalysis by oxynitrilases, also termed hydroxynitrile lyases (HNLs), wording used in this chapter, [3] and by transition metal complexes [4], whereas the relevance of cyclic dipeptides as catalysts is decreasing [2]. 

Aliphatic aldehydes have been converted to their (R)-cyanohydrins using a bipha-sic system to accommodate hydroxynitrile lyase enzyme (from the Japanese apricot, Prunus mume) as the enantioselective catalyst.251... 

F. Effenberger, and K. Pfizenmaier, Enantioselective synthesis of aliphatic (S)-cyanohydrins in organic solvents using hydroxynitrile lyase from Manihot esculenta, Ann. N. Y. Acad. Sci. 1996, 799, 771-776. 

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