biostudies-literaturePressnitz DÖsterreichische ForschungsförderungsgesellschaftAustrian Science Fund FWFFP7 People: Marie-Curie ActionsAustrian Centre of Industrial Biotechnology10683-10687https://www.ebi.ac.uk/biostudies/studies/S-EPMC6146909biostudies-literatureUnknown57(33)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.Angewandte Chemie (International ed. in English)Asymmetric Synthesis of (R)-1-Alkyl-Substituted Tetrahydro-ß-carbolines Catalyzed by Strictosidine Synthases.PMC6146909project W9-01, DK Molecular Enzymologyacibgrant agreement #289646Fischereder EMKroutil WKofler CHammerer LLechner HRichter NPletz JHiebler KPressnitz DEger EfalseAsymmetric Synthesis of (R)-1-Alkyl-Substituted Tetrahydro-ß-carbolines Catalyzed by Strictosidine Synthases.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.2018-01-01T00:00:00Z2018 Aug2026-05-05T23:27:31.278Z2019-03-26T23:57:24ZS-EPMC61469092985252410.1002/anie.201803372