Tautomers of Anthrahydroquinones: Enzymatic Reduction and Implications for Chrysophanol, Monodictyphenone, and Related Xanthone Biosyntheses

Reduction of emodin by sodium dithionite resulted in the formation of two tautomeric forms of emodin hydroquinone. Subsequent conversion by the short-chain dehydrogenase/reductase (SDR) MdpC into the corresponding 3-hydroxy-3,4-dihydroanthracen-1­(2<i>H</i>)-one implies that deoxygenation is the first step in monodictyphenone biosynthesis. Implications for chrysophanol formation as well as reaction sequences in the related xanthone, ergochrome, and bianthraquinone biosyntheses are discussed

Tautomers of Anthrahydroquinones: Enzymatic Reduction and Implications for Chrysophanol, Monodictyphenone, and Related Xanthone Biosyntheses

Reduction of emodin by sodium dithionite resulted in the formation of two tautomeric forms of emodin hydroquinone. Subsequent conversion by the short-chain dehydrogenase/reductase (SDR) MdpC into the corresponding 3-hydroxy-3,4-dihydroanthracen-1­(2<i>H</i>)-one implies that deoxygenation is the first step in monodictyphenone biosynthesis. Implications for chrysophanol formation as well as reaction sequences in the related xanthone, ergochrome, and bianthraquinone biosyntheses are discussed

Highly Efficient One-Pot Multienzyme Cascades for the Stereoselective Synthesis of Natural Naphthalenones

Herein, a biocatalytic cascade containing an ene-reductase (NostocER) and naphthol reductase (tetrahydroxynaphthalene or trihydroxynaphthalene reductase) of Magnaporthe grisea and NADPH is developed. The optimized multienzyme cascade is applied for the one-pot reduction of plumbagin to obtain biologically active cis-(3R,4R)-isoshinanolone, with drcis:trans 98:2 and >99% ee in 96% yield. Furthermore, naturally occurring (+)-isosclerone, (+)-shinanolone, (−)-shinanolone, and (S)-4-hydroxy-3,4-dihydronaphthalen-1­(2H)-one were also synthesized with excellent stereoselectivity and high yields (71–89%) using the enzymatic cascades. The investigation of NostocER–T4HNR-cascade reduction of menadione, plumbagin, and 5-methoxymenadione revealed specificity of tetrahydroxynaphthalene reductase toward these substrates. In addition, the kinetic studies showed a high catalytic efficiency of NostocER and T4HNR toward plumbagin and dihydroplumbagin, respectively, compared to other enzymes

Biomimetic Asymmetric Synthesis of (<i>R</i>)-GTRI-02 and (3<i>S</i>,4<i>R</i>)-3,4-Dihydroxy-3,4-dihydronaphthalen-1(2<i>H</i>)-ones

The NADPH-dependent tetrahydroxynaphthalene reductase (T₄HNR) from <i>Magnaporthe grisea</i> was used for the biomimetic synthesis of (<i>R</i>)-GTRI-02 by stereoselective reduction of 1-(3,6,8-trihydroxy-1-methylnaphthalen-2-yl)ethanone. This also led to the isolation of a (3<i>S</i>,4<i>R</i>)-<i>cis</i>-ketodiol formed by T₄HNR-catalyzed reduction of the corresponding hydroxynaphthoquinone. Flaviolin and lawsone also reduced to corresponding <i>cis</i>-ketodiols in good yields

Biomimetic Asymmetric Synthesis of (<i>R</i>)-GTRI-02 and (3<i>S</i>,4<i>R</i>)-3,4-Dihydroxy-3,4-dihydronaphthalen-1(2<i>H</i>)-ones

The NADPH-dependent tetrahydroxynaphthalene reductase (T₄HNR) from <i>Magnaporthe grisea</i> was used for the biomimetic synthesis of (<i>R</i>)-GTRI-02 by stereoselective reduction of 1-(3,6,8-trihydroxy-1-methylnaphthalen-2-yl)ethanone. This also led to the isolation of a (3<i>S</i>,4<i>R</i>)-<i>cis</i>-ketodiol formed by T₄HNR-catalyzed reduction of the corresponding hydroxynaphthoquinone. Flaviolin and lawsone also reduced to corresponding <i>cis</i>-ketodiols in good yields