Strategic enzymatic enantioselective desymmetrization of prochiral cyclohexa-2,5-dienones
Bhavita Kattula1,2, Anandarao Munakala3, Rajnandani Kashyap1
1Department of Applied Biology, Hyderabad, India. anthony@csiriict.in.
Abstract:
Asymmetric desymmetrization through the selective reduction of one double bond of prochiral 2,5-cyclohexadienones is highly challenging. A novel method has been developed for synthesizing chiral cyclohexenones by employing an ene-reductase (Bacillus subtilis YqjM) enzyme that belongs to the OYE family. Our strategy demonstrates high substrate scope and enantioselectivity towards substrates containing all-carbon as well as heteroatom (O, N)-containing quaternary centers. The mechanistic studies (kH/D = ∼1.8) indicate that hydride transfer is probably the rate-limiting step. Mutation of several active site residues did not affect the stereochemical outcomes. This work provides a convenient way of synthesizing various enantioselective γ,γ-disubstituted cyclohexanones using enzymes.
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