Synthesis of Aliphatic and α‐Halogenated Ketone Cyanohydrins with the Hydroxynitrile Lyase from Manihot esculenta

Abstract

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.

Hydroxynitrile Lyase‐Catalyzed Synthesis of Enantiopure Cyanohydrins in Biocatalytic Active Static Emulsions (BASE) with Suppression of the Non‐Enzymatic Side Reaction

“…Only moderate to low conversions are found with these substrates, starting with 2‐heptanone and gradually decreasing to 2‐decanone (Table 3). Similar results were also recently reported with a classical aqueous‐organic two‐phase system 40. This indicates perfectly that the inclusion immobilization of water into a silicon sphere still represents an aqueous‐organic two‐phase system, but with an exceptional high phase ratio between bulk organic and encapsulated aqueous phase (aqueous pools).…”

A full picture of enzymatic catalysis by hydroxynitrile lyases from Hevea brasiliensis: protonation dependent reaction steps and residue-gated movement of the substrate and the product

“…4,5 The reverse in vivo reactions may also occur under different conditions, with the efficient enantioselectivity for the synthesis of chiral compounds. [6][7][8][9][10][11][12] In recent years, HNLs have been successfully utilized in the production of pharmaceuticals and agrochemicals owing to their importance in biocatalytic retrosynthesis. [13][14][15][16][17][18][19][20] Certainly, an improved understanding of the enzymatic catalysis mechanism of HNLs can potentially further optimize the production processes in industry and help the rational design of biocatalysts.…”

Building Up Quaternary Stereocenters Through Biocatalyzed Direct Insertion of Carbon Nucleophiles on Ketones

“…However, in the literature several examples of both ketone cyanohydrin enantiomers obtained with excellent ee and satisfactory yield starting from methyl ketones are reported . More recently, a comprehensive study toward ketone substrate compatibility of ( S )‐selective hydroxynitrile lyase from Manihot esculenta ( Me HNL), under two‐phase conditions (preferred in industrial applications) consisting of pH 4 or pH 5 buffer and diisopropyl ether (DIPE), with hydrogen cyanide at 10 °C, has been undertaken . Aliphatic methyl ketones have been converted into the corresponding cyanohydrins with enantioselectivities which range from moderate to high along with the increase of the steric hindrance difference between methyl and the alkyl chains bonded to the carbonyl group (Table ).…”

“…On the other hand, substrates with long side chains exhibited significantly reduced reactivity. In fact, to obtain acceptable conversions in the cases of 2‐nonanone and 2‐decanone, reaction times have been prolonged to 22.5 hours and citrate buffer pH 5 has been used, although a slight drop of enantioselectivity occurred …”

“…A further adjustment to pH 6 determined an increase of the non‐enzymatic reaction. However, a strong drop in the reactivity have been observed compared to aliphatic methyl ketones …”