Asymmetric Biocatalytic Synthesis of 1‐Aryltetrahydro‐β‐carbolines Enabled by "Substrate Walking". Issue 69 (3rd November 2020)

• Record Type: Journal Article
• Authors: Eger, Elisabeth; Schrittwieser, Joerg H.; Wetzl, Dennis; Iding, Hans; Kuhn, Bernd; Kroutil, Wolfgang
• Is Part Of: Chemistry. Volume 26:Issue 69(2020)
• Page Start: 16281
• Page End: 16285
• Publication Date: 2020-11-03
• Subjects: asymmetric catalysis -- biocatalysis -- carbolines -- enzyme engineering -- Pictet–Spengler reaction; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202004449
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Stereoselective catalysts for the Pictet–Spengler reaction of tryptamines and aldehydes may allow a simple and fast approach to chiral 1‐substituted tetrahydro‐β‐carbolines. Although biocatalysts have previously been employed for the Pictet–Spengler reaction, not a single one accepts benzaldehyde and its substituted derivatives. To address this challenge, a combination of substrate walking and transfer of beneficial mutations between different wild‐type backbones was used to develop a strictosidine synthase from Rauvolfia serpentina ( Rs STR) into a suitable enzyme for the asymmetric Pictet–Spengler condensation of tryptamine and benzaldehyde derivatives. The double variant Rs STR V176L/V208A accepted various ortho ‐, meta ‐ and para ‐substituted benzaldehydes and produced the corresponding chiral 1‐aryl‐tetrahydro‐β‐carbolines with up to 99 % enantiomeric excess. Abstract : Walking to new frontiers : Taking the challenge that not a single biocatalyst was available for the Pictet–Spengler reaction with benzaldehyde derivatives, modern tools of enzyme engineering were applied in a joined forces approach. Thus, a catalyst displaying the desired activity was created, giving optically enriched products with up to 99 % ee .