Da-Cheng Yang

Biocatalytic one-pot three-component synthesis of 3,3′-disubstituted oxindoles and spirooxindole pyrans using α-amylase from hog pancreas

α-Amylase from hog pancreas displayed catalytic promiscuity in three-component reaction for the synthesis of 3,3′-disubstituted oxindoles and spirooxindole pyrans. The reactions between isatins, malononitrile and active methyl or active methylene compounds (acetone, nitromethane, indole, acetylacetone, 4-hydroxylcoumarin and dimedone) offered corresponding products via Knoevenagel/Michael reactions or Knoevenagel/Michael/cyclization reactions in one pot with high to excellent yields of up to 98% under mild reaction conditions. The α-amylase showed a broad spectrum of adaptability to various substrates. A possible mechanism of the α-amylase catalyzed three-component reaction was proposed.

Chlorophyll-Catalyzed Visible-Light-Mediated Synthesis of Tetrahydroquinolines from N,N-Dimethylanilines and Maleimides

Natural pigment chlorophyll was used as a green photosensitizer for the first time in a visible-light photoredox catalysis for the efficient synthesis of tetrahydroquinolines from N,N-dimethylanilines and maleimides in an air atmosphere. The reaction involves direct cyclization via an sp3 C-H bond functionalization process to afford products in moderate to high yields (61-98%) from a wide range of substrates with a low loading of chlorophyll under mild conditions. This work demonstrates the potential benefits of chlorophyll as photosensitizer in visible light catalysis.

Combining enzyme and photoredox catalysis for aminoalkylation of indoles via a relay catalysis strategy in one pot

We report a novel strategy for combining enzyme and visible-light for mild aminoalkylation of indoles. This method features a relay catalysis protocol consisting of enzyme-catalyzed hydrolysis, visible-light excited decarboxylation, and subsequent oxidization of α-amino radicals and the Friedel–Crafts reaction of the iminium ion with indoles. The α-amino-alkylation products were obtained in good to excellent yields (up to 96%) with a wide range of substrates. This work demonstrates the potential benefits of combining an enzyme and photocatalyst in a relay catalysis reaction.

Biocatalytic asymmetric Mannich reaction of ketimines using wheat germ lipase

A highly enantioselective Mannich reaction between 3-substituted-2H-1,4-benzoxazines and acetone catalyzed by lipase from wheat germ type I (WGL) is described. Enantioselectivity of up to 95% ee was achieved in DMSO at 25 °C. This research provides a new and simple method for the synthesis of β-amino ketone derivatives and promotes the development of enzyme-catalyzed Mannich reactions.

The α-chymotrypsin-catalyzed Povarov reaction: one-pot synthesis of tetrahydroquinoline derivatives

The three-component one-pot Povarov reaction for the synthesis of tetrahydroquinoline derivatives was catalyzed by α-chymotrypsin from bovine pancreas (BPC) for the first time. The products were obtained in moderate to good yields with a wide range of substrates. Based on the control and comparison experiments of natural and promiscuous activities, a tentative mechanism was discussed. Molecular docking and energy calculation of quantum chemistry were used to explain the experimental results in theory. As a novel case of enzyme catalytic promiscuity, this work expands the application of BPC. Exploring the untapped catalytic promiscuity of natural enzymes may also provide useful information about enzyme evolution.

Enzyme-Catalyzed Asymmetric Domino Thia-Michael/Aldol Condensation Using Pepsin

The novel catalytic promiscuity of pepsin from porcine gastric mucosa for the asymmetric catalysis of the domino thia-Michael/aldol condensation reaction in MeCN and buffer was discovered for the first time. Broad substrate specificity was tested, and a series of corresponding products were obtained with enantioselectivities of up to 84% ee. This specific catalysis was demonstrated by using recombinant pepsin and control experiments with denatured and inhibited pepsin. The reaction was also shown to occur in the active site by site-directed mutagenesis (the Asp32Ala mutant of pepsin), and a possible mechanism was proposed.

Enzyme-catalyzed domino reaction: efficient construction of spirocyclic oxindole skeleton using porcine pepsin

Pepsin from porcine gastric mucosa was used as a sustainable and environmentally friendly biocatalyst in the domino Knoevenagel/Michael/Michael reaction for the synthesis of spirooxindole derivatives in methanol. A wide range of isatins and α,β-unsaturated ketones reacting with malononitrile provided the corresponding products in yields of up to 99% with diastereoselectivities of up to >99 : 1 dr. This pepsin-catalyzed domino reaction provided a novel case of enzyme catalytic promiscuity.

Catalyst-free synthesis of trisubstituted tetrahydrothiophenes in water via a cascade sulfa-Michael/aldol (Henry) type reaction

A simple, efficient, eco-friendly and catalyst-free procedure was developed for the construction of trisubstituted tetrahydrothiophenes via sulfa-Michael/aldol (Henry) cascade reaction in water. The protocol, simply utilizing readily-available starting materials under clean reaction conditions, provided an alternative and highly attractive approach to a series of tetrahydrothiophene derivatives from a wide range of substrates in good yields (up to 93%) with excellent diastereoselectivities (up to >99 : 1).

Earthworm Is a Versatile and Sustainable Biocatalyst for Organic Synthesis

A crude extract of earthworms was used as an eco-friendly, environmentally benign, and easily accessible biocatalyst for various organic synthesis including the asymmetric direct aldol and Mannich reactions, Henry and Biginelli reactions, direct three-component aza-Diels-Alder reactions for the synthesis of isoquinuclidines, and domino reactions for the synthesis of coumarins. Most of these reactions have never before seen in nature, and moderate to good enantioselectivities in aldol and Mannich reactions were obtained with this earthworm catalyst. The products can be obtained in preparatively useful yields, and the procedure does not require any additional cofactors or special equipment. This work provides an example of a practical way to use sustainable catalysts from nature.