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( S )‐Selectivity in Phenylacetyl Carbinol Synthesis Using the Wild‐Type Enzyme Acetoin:Dichlorophenolindophenol Oxidoreductase from Bacillus licheniformis
Author(s) -
Giovannini Pier Paolo,
Lerin Lindomar Alberto,
Müller Michael,
Bernacchia Giovanni,
Bastiani Morena De,
Catani Martina,
Di Carmine Graziano,
Massi Alessandro
Publication year - 2016
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201600359
Subject(s) - chemistry , benzaldehyde , chemoselectivity , selectivity , aldehyde , acetoin , oxidoreductase , cyclohexanone , bacillus licheniformis , enzyme , biocatalysis , stereochemistry , combinatorial chemistry , organic chemistry , catalysis , fermentation , reaction mechanism , biology , bacillus subtilis , bacteria , genetics
Abstract Thiamine diphosphate (ThDP)‐dependent enzymes are well known biocatalysts for the asymmetric synthesis of α‐hydroxy ketones with preferential ( R )‐selectivity. Pharmaceutically relevant phenylacetyl carbinol (PAC) has been prepared with absolute ( S )‐configuration only on a few occasions using enzyme variants suitably designed through rational site‐directed mutagenesis approaches. Herein, we describe the synthesis of ( S )‐phenylacetyl carbinol products with extended reaction scope employing the readily available wild‐type ThDP‐dependent enzyme acetoin:dichlorophenolindophenol oxidoreductase (Ao:DCPIP OR) from Bacillus licheniformis . On a semipreparative scale, cross‐benzoin‐like condensations of methylacetoin (donor) and differently substituted benzaldehydes proceed with almost complete chemoselectivity yielding the target ( S )‐1‐hydroxy‐1‐phenylpropan‐2‐one derivatives with high conversion efficiencies (up to 95%) and good enantioselectivities (up to 99%). Ao:DCPIP OR accepts hydroxy‐ and nitrobenzaldehydes and also sterically demanding substrates such as 1‐naphthaldehyde and 4‐( tert ‐butyl)benzaldehyde, which are typically poor acceptors in enzymatic transformations. The explorative synthesis of ( S )‐phenylpropionyl carbinol mediated by Ao:DCPIP OR via carboligation of benzaldehyde with 3,4‐hexanedione is also reported.