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

Abstract

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.