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Asymmetric Biocatalytic Synthesis of 1-Aryltetrahydro-?-carbolines Enabled by "Substrate Walking".

ABSTRACT: Stereoselective catalysts for the Pictet-Spengler reaction of tryptamines and aldehydes may allow a simple and fast approach to chiral 1-substituted tetrahydro-?-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 (RsSTR) into a suitable enzyme for the asymmetric Pictet-Spengler condensation of tryptamine and benzaldehyde derivatives. The double variant RsSTR V176L/V208A accepted various ortho-, meta- and para-substituted benzaldehydes and produced the corresponding chiral 1-aryl-tetrahydro-?-carbolines with up to 99?% enantiomeric excess.

SUBMITTER: Eger E

PROVIDER: S-EPMC7756766 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Asymmetric Biocatalytic Synthesis of 1-Aryltetrahydro-β-carbolines Enabled by "Substrate Walking".

Eger Elisabeth E Schrittwieser Joerg H JH Wetzl Dennis D Iding Hans H Kuhn Bernd B Kroutil Wolfgang W

Chemistry (Weinheim an der Bergstrasse, Germany) 20201103 69

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 strictosid ...[more]

PMID: 33017078

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