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Asymmetric Biocatalytic Synthesis of 1‐Aryltetrahydro‐β‐carbolines Enabled by “Substrate Walking”
Author(s) -
Eger Elisabeth,
Schrittwieser Joerg H.,
Wetzl Dennis,
Iding Hans,
Kuhn Bernd,
Kroutil Wolfgang
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202004449
Subject(s) - tryptamine , benzaldehyde , tryptamines , pictet–spengler reaction , substrate (aquarium) , chemistry , stereoselectivity , enantioselective synthesis , enantiomeric excess , enantiomer , condensation , catalysis , organic chemistry , combinatorial chemistry , biochemistry , biology , ecology , physics , thermodynamics
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.