Asymmetric Synthesis of (R)‐1‐Alkyl‐Substituted Tetrahydro‐ß‐carbolines Catalyzed by Strictosidine Synthases. (21st June 2018)

• Record Type: Journal Article
• Authors: Pressnitz, Desiree; Fischereder, Eva‐Maria; Pletz, Jakob; Kofler, Christina; Hammerer, Lucas; Hiebler, Katharina; Lechner, Horst; Richter, Nina; Eger, Elisabeth; Kroutil, Wolfgang
• Is Part Of: Angewandte Chemie. Volume 130:Number 33(2018)
• Page Start: 10843
• Page End: 10847
• Publication Date: 2018-06-21
• Subjects: Asymmetrische Katalyse -- Biokatalyse -- Pictet-Spengler-Reaktion -- Strictosidin-Synthasen -- Tetrahydro-β-carboline; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201803372
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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.