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

Stereoselective Biocatalytic Synthesis of (S)‐2‐Hydroxy‐2‐Methylbutyric Acid via Substrate Engineering by Using “Thio‐Disguised” Precursors and Oxynitrilase Catalysis

“…[26] This unsuitability of 1 as a substrate is in accord with the reported synthesis of (R)-cyanohydrin 3 using HNL from Prunus amygdalus (PaHNL) with 76 % ee [12] and from Linum usitatissimum HNL with 77 % ee. [27] Very recently 2-butanone (1) has again been transformed into the (R)-cyanohydrin with a new HNL from Prunus mume to give 72 % ee.…”

“…[9] With respect to the industrial application of HNLs, for example, (S)-3-phenoxybenzaldehyde cyanohydrin, an intermediate for synthetic pyrethroids, was produced on large industrial scale. [10] Regarding ketones as educts for the biocatalysed cyanide attack, besides methyl and ethyl ketones [11][12][13][14][15] fewer results on cyclic ketones were published. [16][17][18] Surprisingly, although acalyphin, a cyanogenic plant glycoside, emerges from a pyridone derivative, [19] except our primary publication [20] and the results presented here, no HNL-catalysed HCN addition to heterocyclic ketones has been reported up to date.…”

Linum usitatissimum Hydroxynitrile Lyase Cross‐Linked Enzyme Aggregates: A Recyclable Enantioselective Catalyst

“…[18] We first optimized LuCLEA preparation on a 90-mL scale and noticed that freeze drying affected the biocatalyst activity. From results obtained in earlier samples it was clear that the CLEA could not be freeze-dried overnight and should be promptly stored at À20 8C when the biocatalyst is sufficiently dry.…”

“…Synthetic approach towards (R)-enantioenriched 2-hydroxy-2-methylbutyric acid (R)-I. [18,19] while the Linum usitatissimum HNL (LuHNL) was reported to give good to very good enantiopurities of the cyanohydrin intermediate. [20,21] We recently described that immobilizing the HNLs from Prunus amygdalus, Hevea brasiliensis and Manihot esculenta as cross-linked enzyme aggregates (CLEAs) can improve their stability and ease their recycling.…”

Screening for New Hydroxynitrilases from Plants

“…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%. Enantiomeric excess was calculated from the peak areas of (R)-2-hydroxy-2-methylpentanoic acid methyl ester, which had been synthesized with Prunus dulcis HNL 15) and (S)-2-hydroxy-2-methylpentanoic acid methyl ester, both synthesized and detected as one of the racemates. …”