title: Enantiocomplementary Synthesis of γ-Nitroketones Using Designed and Evolved Carboligases.
abstract: Artificial enzymes created by computational design and directed evolution are versatile biocatalysts whose promiscuous activities represent potentially attractive starting points for divergent evolution in the laboratory. The artificial aldolase RA95.5-8, for example, exploits amine catalysis to promote mechanistically diverse carboligations. Here we report that RA95.5-8 variants catalyze the asymmetric synthesis of γ-nitroketones via two alternative enantiocomplementary Michael-type reactions: enamine-mediated addition of acetone to nitrostyrenes, and nitroalkane addition to conjugated ketones activated as iminium ions. In addition, a cascade of three aldolase-catalyzed reactions enables one-pot assembly of γ-nitroketones from three simpler building blocks. Together, our results highlight the chemical versatility of artificial aldolases for the practical synthesis of important chiral synthons.
authors.affiliation: Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
authors.forename: Xavier
authors.identifier: 0000-0003-3663-8420
authors.initials: X
authors.lastname: Garrabou
authors.affiliation: Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Verez
authors.affiliation: Laboratory of Organic Chemistry, ETH Zurich , 8093 Zurich, Switzerland.
authors.forename: Donald
authors.initials: D
authors.lastname: Hilvert
mesh_terms: D000446:Aldehyde-Lyases / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D007659:Ketones / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D009574:Nitro Compounds / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D007659:Ketones; D009574:Nitro Compounds; D000446:Aldehyde-Lyases