Nicotinamide Adenine Dinucleotide-Dependent Redox-Neutral Convergent Cascade for Lactonizations with Type II Flavin-Containing Monooxygenase

A nicotinamide adenine dinucleotide (NADH)-dependent redox-neutral convergent cascade composed of a recently discovered type II flavin-containing monooxygenase (FMO E) and horse liver alcohol dehydrogenase (HLADH) has been established. Two model reaction cascades were analyzed for the synthesis of g-butyrolactone and chiral bicyclic lactones. In the former cascade, all substrates were converted into one single product g-butyrolactone with high atom efficiency. More than 130 mM g-butyrolactone were obtained when applying 100 mM cyclobutanone and 50 mM 1,4-butanediol in this cascade. In the second cascade where bicyclo[4.2.0]octan-7-one and cis1,2-cyclohexanedimethanol were coupled, the ketone substrate was converted to the corresponding normal lactone with an ee value of 89–74% (3aS, 7aS) by FMO E alone and the abnormal lactone with an ee value of >99% (3aR, 7aS) was formed by both HLADH and FMO E.