title: Stereoselective biocatalytic synthesis of (S)-2-hydroxy-2-methylbutyric acid via substrate engineering by using "thio-disguised" precursors and oxynitrilase catalysis.
abstract: 3-Tetrahydrothiophenone (4) and 4-phenylthiobutan-2-one (7) were used as masked 2-butanone equivalents to give the corresponding cyanohydrins 5 (79 % yield, 91 % ee) and 8 (95 % yield, 96 % ee) in an enzymatic cyanohydrin reaction applying the hydroxynitrile lyase (HNL) from Hevea brasiliensis. After hydrolysis and desulphurisation the desired intermediate (S)-2-hydroxy-2-methylbutyric acid (10) was obtained with 99 % ee. Interestingly, when applying (R)-selective HNL from Prunus amygdalus again the (S)-cyanohydrin 5 was formed (62 % ee). The absolute configuration of 5 was verified by crystal structure determination of the corresponding hydrolysis derived carboxylate. The fact that both enzymes yield the same enantiomer was analysed and interpreted by molecular modelling calculations.
authors.affiliation: Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 16, 8010 Graz, Austria.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Fechter
authors.forename: Karl
authors.initials: K
authors.lastname: Gruber
authors.forename: Manuela
authors.initials: M
authors.lastname: Avi
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Skranc
authors.forename: Christian
authors.initials: C
authors.lastname: Schuster
authors.forename: Peter
authors.initials: P
authors.lastname: Pöchlauer
authors.forename: Kurt O
authors.initials: KO
authors.lastname: Klepp
authors.forename: Herfried
authors.initials: H
authors.lastname: Griengl
mesh_terms: D000446:Aldehyde-Lyases / Q000737:chemistry / Q000378:metabolism*; D002087:Butyrates / Q000138:chemical synthesis*; D002384:Catalysis; D018360:Crystallography, X-Ray; D028482:Hevea / Q000201:enzymology*; D006868:Hydrolysis; D006880:Hydroxy Acids; D008956:Models, Chemical; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism*; D027861:Prunus / Q000201:enzymology*; D013237:Stereoisomerism
chemical_list: C521666:2-hydroxy-2-methylbutyric acid; D002087:Butyrates; D006880:Hydroxy Acids; D009570:Nitriles; C430593:cyanohydrin; D000446:Aldehyde-Lyases; C021541:mandelonitrile lyase; C079359:hydroxymandelonitrile lyase