This account focuses on the application
of ω-transaminases,
lyases, and oxidases for the preparation of amines considering mainly
work from our own lab. Examples are given to access α-chiral
primary amines from the corresponding ketones as well as terminal
amines from primary alcohols via a two-step biocascade. 2,6-Disubstituted
piperidines, as examples for secondary amines, are prepared by biocatalytical
regioselective asymmetric monoamination of designated diketones followed
by spontaneous ring closure and a subsequent diastereoselective reduction
step. Optically pure tert-amines such as berbines
and N-methyl benzylisoquinolines are obtained by
kinetic resolution via an enantioselective aerobic oxidative C–C
bond formation.
Stereoselective methods for the synthesis of tetrahydro‐ß‐carbolines are of significant interest due to the broad spectrum of biological activity of the target molecules. In the plant kingdom, strictosidine synthases catalyze the C−C coupling through a Pictet–Spengler reaction of tryptamine and secologanin to exclusively form the (S)‐configured tetrahydro‐ß‐carboline (S)‐strictosidine. Investigating the biocatalytic Pictet–Spengler reaction of tryptamine with small‐molecular‐weight aliphatic aldehydes revealed that the strictosidine synthases give unexpectedly access to the (R)‐configured product. Developing an efficient expression method for the enzyme allowed the preparative transformation of various aldehydes, giving the products with up to >98 % ee. With this tool in hand, a chemoenzymatic two‐step synthesis of (R)‐harmicine was achieved, giving (R)‐harmicine in 67 % overall yield in optically pure form.
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