Asymmetric Synthesis of O-Protected Acyloins Using Enoate Reductases: Stereochemical Control through Protecting Group Modification

O-Protected cyclic acyloins were obtained in nonracemic form through asymmetric bioreduction of alpha,beta-unsaturated alkoxy ketones by using 11 different enoate reductases from the Old Yellow Enzyme family. The stereochemical outcome of the biotransformation could be switched by variation of the O-protecting group or by the ring size of the substrate, which allows access to both stereoisomers in up to >97% ee Whereas alpha-alkoxy enones were readily accepted as substrates, beta-analogs were not converted. Overall, alpha-alkoxy enones represent a novel type of substrate for flavin-dependent ene-reductases.