title: Enzymatic diastereo- and enantioselective synthesis of α-alkyl-α,β-dihydroxyketones.
abstract: An enzymatic strategy for the preparation of optically pure α-alkyl-α,β-dihydroxyketones is reported. Homo- and cross-coupling reactions of α-diketones catalyzed by acetylacetoin synthase (AAS) produce a set of α-alkyl-α-hydroxy-β-diketones (30-60%, ee 67-90%), which in turn are reduced regio-, diastereo-, and enantioselectively to the corresponding chiral α-alkyl-α,β-dihydroxyketones (60-70%, ee >95%) using acetylacetoin reductase (AAR) as catalyst. Both enzymes are obtained from Bacillus licheniformis and used in a crude form. The relative syn stereochemistry of the enantiopure α,β-dihydroxy products is assigned by NOE experiments, whereas their absolute configuration is determined by conversion of the selected 3,4-dihydroxy-3-methyl-pentan-2-one to the natural product (+)-citreodiol.
authors: Dipartimento di Chimica, Università di Ferrara, Ferrara, Italy. gvnppl@unife.it
authors: Pier Paolo
authors: PP
authors: Giovannini
authors: Giancarlo
authors: G
authors: Fantin
authors: Alessandro
authors: A
authors: Massi
authors: Valentina
authors: V
authors: Venturi
authors: Paola
authors: P
authors: Pedrini
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000478:Alkylation; D006900:Hydroxylation; D007659:Ketones / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D007659:Ketones; D000429:Alcohol Oxidoreductases; C118320:acetylacetoin reductase