Deracemization cyclic secondary amines

In order to extend the approach to include deracemization of chiral secondary amines, this group carried out directed evolution on the monoamine oxidase (MAO) enzyme MAO-N (Scheme 2.32). A new variant was identified with improved catalytic properties towards a cyclic secondary amine 64, the substrate used in the evolution experiments. This new variant had a single point mutation, lle246Met, and was found to have improved catalytic properties towards a number of other cyclic secondary amines. The new variant was used in the deracemization of rac-64 yielding (R)-64 in high yield and enantiomeric excess [34]. 

Carr, R., Alexeeva, M., Dawson, M. J., Gotor-Fernandez, V., Humphrey, C. E., and Turner, N. J. 2005. Directed evolution of oxidase for the preparative deracemization of cyclic secondary amines. Chem. Bio. Chem.,6, 637-639. 

Cyclic secondary amines [102] have been successfully deracemized via directed evolution of the monoamine oxidase from A. niger. The new variant displayed high catalytic activity and enantioselectivity towards cyclic secondary amines which could be subjected to reduction using ammonia borane to give the enantiomericaUy pure amine (Scheme 4.47). 

Similar to AAOs, MAO can also be employed either in the stereoinversion starting from an enantiopure amine or in the deracemization starting from the racemate vide supra) [18]. Both approaches have been proven to be remarkably efficient for chiral amine synthesis, in particular for cyclic secondary and tertiary structures. Conversely, for acyclic imine intermediates, a competing hydrolysis reaction toward the carbonyl compound is often observed, thus leading to a diminished product yield. This spontaneous hydrolysis was recently exploited for the deracemization cascade reaction combining an (S)-selective MAO with an (R)-selective co-TA (Scheme 2.44) [149]. 

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