文摘
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.