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Asymmetric Synthesis of ( R )‐1‐Alkyl‐Substituted Tetrahydro‐ß‐carbolines Catalyzed by Strictosidine Synthases
Author(s) -
Pressnitz Desiree,
Fischereder EvaMaria,
Pletz Jakob,
Kofler Christina,
Hammerer Lucas,
Hiebler Katharina,
Lechner Horst,
Richter Nina,
Eger Elisabeth,
Kroutil Wolfgang
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201803372
Subject(s) - tryptamine , chemistry , yield (engineering) , biocatalysis , stereoselectivity , alkyl , stereochemistry , enzyme , catalysis , combinatorial chemistry , organic chemistry , biochemistry , reaction mechanism , materials science , metallurgy
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.