Hydroxynitrile

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Two more examples ia Table 5 iaclude the hydrolysis of esters of trans-alcohols that proceed with high efficiency practically regardless of the nature of the substituents (72) and resolution of P-hydroxynitriles with Upase from Pseudomonas sp. In the latter case the enantioselectivity of the hydrolysis was improved by iatroduciag sulfur iato the acyl moiety (73). 

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

Condensation of the anion obtained on reaction of acetonitrile with sodium amide, with o-chlorobenzophenone (36), affords the hydroxynitrile, 37. Catalytic reduction leads to the corresponding amino alcohol (note that the benzhydryl alcohol is not hydrogenolyzed). Reductive alkylation with formaldehyde and hydrogen in the presence of Raney nickel gives the antitussive a-gent, chlorphedianol (39). °... 

Hetero-fused 4/ -pyrans result from the cyclisation of 1,5-hydroxynitriles <96BSF229> and l,S-diketones <96HA567> the latter route can be adapted to give the corresponding thiopyrans. 

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. 

CRYSTAL STRUCTURES OF HYDROXYNITRILE LYASES AND MECHANISM OF CYANOGENESIS... 

Hydroxynitrile formation from acyclic sulphite Merck Co. Landau etal. (1994)... 

Diethylaluminum cyanide can also be used for preparation of (3-hydroxynitriles. 

Intramolecular deoxygenation of alcohols containing double and triple bonds (such as hydroxyalkynes or hydroxynitriles) with ImCSIm leads via the corresponding thio-carbonylimidazolides to five- and six-membered cyclized systems with exocyclic double bonds.[72]... 

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... 

Purkarthofer, T., Skranc, W., Schuster, C. and Griengl, H. (2007) Potential and capabilities of hydroxynitrile lyases as biocatalysts in the chemical industry. Applied Microbiology and Biotechnology, 76, 309—320. 

Effenberger, F., Forster, S. and Wajant, H. (2000) Hydroxynitrile lyases in stereoselective catalysis. Current... 

The reduction of a-hydroxynitriles to yield vicinal amino alcohols is conveniently accomplished with complex metal hydrides for example, lithium aluminum hydride or sodium borohydride [69]. However, it is still worth noting that a two-step chemo-enzymatic synthesis of (R)-2-amino-l-(2-furyl)ethanol for laboratory production was developed followed by successful up-scaling to kilogram scale using NaBH4/CF3COOH as reductant [70],... 

Starting from enantiomerically pure 4-methylsulfanyl-mandelonitrile, thiamphenicol and florfenicol have been enantioselectively synthesized (Figure 5.14). The enantiomerically pure 4-methylsulfanyl-mandelonitrile was obtained by hydrocyanation reaction of 4-methy lsulfany 1-benzaldehyde catalyzed by (M)-hydroxynitrile lyase of Badamu (almond from Xinjiang, China) (Prunus communis L. var. dulcis Borkh), which, after an extensive screening, was found to be a highly effective bio-catalyst for this reaction [85]. 

Dreveny, I., Gruber, K., Glieder, A. et al. (2001) The hydroxynitrile lyase from almond a lyase that looks like an oxidoreductase. Structure (London, England 1993), 9, 803-815. 

Dreveny, I., Kratky, C. and Gruber, K. (2002) The active site of hydroxynitrile lyase from Prunus amygdalus modeling studies provide new insights into the mechanism of cyanogenesis. Protein Science A Publication of the Protein Society, 11, 292-300. 

Hasslacher, M., Schall, M., Hayn, M. et al. (1997) High-level intracellular expression of hydroxynitrile lyase from the tropical rubber tree Hevea brasiliensis in microbial hosts. Protein Expression and Purification, 11, 61-71. 

Zuegg, J., Gruber, K., Gugganig, M. et al. (1999) Three-dimensional structures of enzyme-substrate complexes of the hydroxynitrile lyase from Hevea brasiliensis. Protein Science A Publication of the Protein Society, 8, 1990-2000. 

Wagner, U.G., Hasslacher, M., Griengl, H. et al. (1996) Mechanism of cyanogenesis the crystal structure of hydroxynitrile lyase from Hevea brasiliensis. Structure (London, England 1993), 4, 811-822. 

Lauble, H., Miehlich, B., Forster, S. et al. (2002) Crystal structure of hydroxynitrile lyase from Sorghum bicolor in complex with the inhibitor benzoic acid a novel cyanogenic enzyme. Biochemistry, 41, 12043-12050. 

Wajant, H. and Effenberger, F. (1996) Hydroxynitrile lyases of higher plants. The Journal of Biological Chemistry, 377, 611-617. 

Andexer, J., von Langermann, J., Mell, A. et al. (2007) An R-selective hydroxynitrile lyase from Arabidopsis thaliana with an alpha/beta-hydrolase fold. Angewandte Chemie-International Edition, 46, 8679-8681. 

Hernandez, L., Luna, H., Rulz-Teran, F. and Vazquez, A. (2004) Screening for hydroxynitrile lyase activity in crude preparations of some edible plants. Journal of Molecular Catalysis B-Enzymatic, 30, 105-108. 

Hughes, J., Lakey, J.H. and Hughes, M.A. (1997) Production and characterization of a plant alpha-hydroxynitrile... 

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. 

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