160754-13-2

Upstream product

• 4111-09-5 2-Hydroxy-2-methyl-pentanenitrile 
• 91390-80-6 2-methyl-2-(trimethylsiloxy)pentanenitrile 
• 151-50-8 potassium cyanide 
• 107-87-9 2-Pentanone 
• 74-90-8 hydrogen cyanide 

Relevant academic research and scientific papers

Synthesis of aliphatic and α-halogenated ketone cyanohydrins with the hydroxynitrile lyase from Manihot esculenta

The potential of the hydroxynitrile lyase from Manihot esculenta towards ketone substrates was investigated. It was observed that the length of the aliphatic chain is a key parameter for the conversion of aliphatic, non-branched ketones. Smaller substrates are readily converted with high enantioselectivites, but the elongation of the chain length causes a significant loss in enzyme activity. For a number of halogenated, herein especially fluorinated, acetophenone derivatives the corresponding cyanohydrins have been synthesized with good to moderate enantioselectivities. Overcoming limitations: Ketone cyanohydrins are extremely useful intermediates for the synthesis of unusual tertiary alcohols. In this contribution, the limits of the hydroxynitrile lyase from Manihot esculenta towards such substrates are investigated and evaluated. High enantioselectivities are obtained in a simple two-phase system, even with very challenging fluorinated acetophenone derivatives.

Investigation of lewis acid versus lewis base catalysis in asymmetric cyanohydrin synthesis

The asymmetric addition of trimethylsilyl cyanide to aldehydes can be catalysed by Lewis acids and/or Lewis bases, which activate the aldehyde and trimethylsilyl cyanide, respectively. It is not always apparent from the structure of the catalyst whether Lewis acid or Lewis base catalysis predominates. To investigate this in the context of using salen complexes of titanium, vanadium and aluminium as catalysts, a Hammett analysis of asymmetric cyanohydrin synthesis was undertaken. When Lewis acid catalysis is dominant, a significantly positive reaction constant is observed, whereas reactions dominated by Lewis base catalysis give much smaller reaction constants. [{Ti(salen)O}2] was found to show the highest degree of Lewis acid catalysis, whereas two [VO(salen)X] (X = EtOSO3 or NCS) complexes both displayed lower degrees of Lewis acid catalysis. In the case of reactions catalysed by [{Al(salen)}2O] and triphenyl- phosphine oxide, a non-linear Ham- mett plot was observed, which is indicative of a change in mechanism with increasing Lewis base catalysis as the carbonyl compound becomes more electron-deficient. These results suggested that the aluminium complex/tri- phenylphosphine oxide catalyst system should also catalyse the asymmetric addition of trimethylsilyl cyanide to ke- tones and this was found to be the case.

A new (R)-hydroxynitrile lyase from Prunus mume: Asymmetric synthesis of cyanohydrins

A new hydroxynitrile lyase (HNL) was isolated from the seed of Japanese apricot (Prunus mume). The enzyme has similar properties with HNL isolated from other Prunus species and is FAD containing enzyme. It accepts a large number of unnatural substrates (benzaldehyde and its variant) for the addition of HCN to produce the corresponding cyanohydrins in excellent optical and chemical yields. A new HPLC based enantioselective assay technique was developed for the enzyme, which promotes the addition of KCN to benzaldehyde in a buffered solution (pH=4.5).

Screening for new hydroxynitrilases from plants

We established a simple HPLC method to determine the activity and stereochemistry of the chiral mandelonitrile synthesized from benzaldehyde and cyanide, and applied it to screen for hydroxynitrile lyase (HNL) activity of plant origin. A total of 163 species of plants among 74 families were examined for (R)- and (S)-HNL activities using the method. We discovered that homogenate of leaves of Baliospermum montanum shows (S)-HNL activity, while leaves and seeds from Passiflora edulis, and seeds from Eriobotrya japonica, Chaenomles sinensis, Sorbus aucuparia, Prunus mume, and Prunus persica show (R)-HNL activity. Partially purified (R)-HNLs from Passiflora edulis and Eriobotrya japonica acted not only on benzaldehyde but also on aliphatic ketone. The enantiomeric excess of (R)-methylpropylketone cyanohydrin synthesized from 2-pentanone using homogenate from leaves of Passiflora edulis was 87.0%, and that of (R)-mandelonitrile synthesized by homogenate from seeds of Eriobotrya japonica was 85.0%.

Enzyme catalysed formation of (S)-cyanohydrins derived from aldehydes and ketones in a biphasic solvent system

By employing a vigorously stirred two phase system aqueous buffer/organic solvent and using the hydroxynitrile lyase from Hevea brasiliensis as biocatalyst enantiopure (S)-cyanohydrins from aliphatic, unsaturated, aromatic and heteroaromatic aldehydes and methyl alkyl and methyl phenyl ketones are obtained in high yield and in general 98-99% enantiomeric excess.

Ueber die erste rekombinante Hydroxynitril-Lyase und ihre Anwendung in der Synthese von (S)-Cyanhydrinen

Keywords: Asymmetrische Synthesen; (S)-Cyanhydrine; Enzymkatalyse; Lyasen

Optically Active (S)-Ketone- and (R)-Aldehyde-cyanohydrins via an (R)-Oxynitrilase-catalysed Transcyanation. Chemoenzymatic Syntheses of 2-Cyanotetrahydrofuran and 2-Cyanotetrahydropyran

(R)-Oxynitrilase catalyses the enantioselective decyanation of racemic ketone cyanohydrins and the enantioselective addition of HCN to ω-bromoaldehydes in one step.

(R)-Oxynitrilase Catalyzed Synthesis of (R)-Ketone Cyanohydrins

(R)-Oxynitrilase from almonds (Prunus amygdalus) catalyzed the enantioselective addition of HCN to ethyl alkyl ketones 1 in diisopropyl ether yielding (R)-ethyl alkyl ketone cyanohydrins (R)-2, which are hydrolyzed under acid catalysis to give the α-hydroxy acids (R)-3.This (R)-oxynitrilase also catalyzes the enantioselective addition in aqueous citrate buffer (50 mM, pH 4.0), as demonstrated for the preparation of (R)-methyl alkyl ketone cyanohydrins (R)-5 which are obtained in high enantiomeric excesses comparable to those in diisopropyl ether as solvent.

Synthese und Reaktionen optisch aktiver Cyanhydrine

Bei der grossen Bedeutung, die Cyanhydrine in der Technik und in der Organischen Chemie immer schon hatten, ist es erstaunlich, dass optisch aktive Cyanhydrine erst in den letzten Jahren intensiver untersucht und in der Synthese eingesetzt wurden.Der Grund dafuer ist wohl darin zu sehen, dass es erst in neurerer Zeit gelungen ist, chirale Cyanhydrine, hauptsaechlich mit enzymatischen Methoden, relativ einfach und in hoher optischer Reinheit herzustellen.Chirale Cyanhydrine sind, zumeist als Glycoside geschuetzt, in der Natur weit verbreitet.Annaehernd dreitausend Pflanzen und vielen Insekten dienen sie unter anderem als Abwehrstoffe gegen "Fresser".Ihre grosse Bedeutung in der Organischen Chemie beruht auf ihrem enormen Synthesepotential fuer die Gewinnung anderer wichtiger chiraler Verbindungen.In Wirkstoffen sind chirale Cyanhydrinbausteine nur vereinzelt enthalten.Wegen der Notwendigkeit, bei neuen Wirksubstanzen mit Chiralitaetszentren, saemtliche Stereoisomere herzustellen und sie bezueglich ihres Wirkungsspektrums sowie ihres Metabolismus zu untersuchen, ist die Entwicklung neuer und einfacher stereoselektiver Synthesen erforderlich.Chirale Cyanhydrine koennen hierbei wertwolle Ausgangsverbindungen sein.Im vorliegenden Artikel werden folgende Themen behandelt: die durch die Enzyme (R)- oder (S)-Oxynitrilase katalysierte enantioselektive Addition von Blausaeure an Aldehyde und Ketone zu (R)- bzw. (S)-Cyanhydrinen; die durch cyclische Dipeptide katalysierte enantioselektive Addition von Blausaeure an Aldehyde; die durch Lipasen und Esterasen katalysierte enantioselektive Hydrolyse bzw.Veresterung racemischer Cyanhydrine und Cyanhydrinester; Folgereaktionen der Nitrilgruppe chiraler Cyanhydrine zu optisch aktiven α-Hydroxycarbonsaeuren, α-Hydroxyaldehyden, α-Hydroxyketonen und 2-Aminoalkoholen; Folgereaktionen der OH-Gruppe chiraler Cyanhydrine durch Sulfonylaktivierung und anschliessende stereoselektive Substitution mit Nucleophilen unter Konfigurationsumkehr zu optisch aktiven α-Azidonitrilen, α-Aminonitrilen unf α-Fluornitrilen.

Enzyme-catalyzed synthesis of (R)-ketone-cyanohydrins and their hydrolysis to (R)-α-hydroxy-α-methyl-carboxylic acids

(R)-Ketone-cyanohydrins (R)-2 are obtained with high enantioselectivity from aliphatic ketones 1 and HCN in organic solvents using (R)-oxynitrilase ( EC 4.1.2.10) as catalyst. Acid catalyzed hydrolysis of the cyanohydrins (R)-2 affords the corresponding (R)-α-hydroxy-α-methyl-carboxylic acids (R)-3 without measurable racemization.