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 γ ‐butyrolactone and chiral bicyclic lactones. In the former cascade, all substrates were converted into one single product γ ‐butyrolactone with high atom efficiency. More than 130 mM γ ‐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 cis‐1,2‐cyclohexanedimethanol were coupled, the ketone substrate was converted to the corresponding normal lactone with an ee value of 89–74% (3a S , 7a S ) by FMO−E alone and the abnormal lactone with an ee value of >99% (3a R , 7a S ) was formed by both HLADH and FMO−E. magnified image