Enzymatic and Chemoenzymatic Three-Step Cascades for the Synthesis of Stereochemically Complementary Trisubstituted Tetrahydroisoquinolines
| Autor: | Vanessa Erdmann, Jianxiong Zhao, Wolfgang Kroutil, Robert C. Simon, Dörte Rother, John M. Ward, Benjamin R. Lichman, Helen C. Hailes |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
biocatalysis
Transamination Stereochemistry Substituent Chemistry Techniques Synthetic norcoclaurine synthase 010402 general chemistry 01 natural sciences Cofactor Catalysis chemistry.chemical_compound Thalictrum Tetrahydroisoquinolines medicine Escherichia coli Carbon-Nitrogen Ligases Transaminases chemistry.chemical_classification Cascade Reactions biology 010405 organic chemistry Chemistry Chromobacterium Communication Enantioselective synthesis asymmetric catalysis Stereoisomerism General Chemistry Communications 0104 chemical sciences Acetolactate Synthase Enzyme Biocatalysis THIQ ddc:540 biology.protein chemoenzymatic cascades medicine.drug |
| Zdroj: | Angewandte Chemie (International Ed. in English) Angewandte Chemie / International edition 56(41), 12503-12507 (2017). doi:10.1002/anie.201705855 |
| ISSN: | 1433-7851 |
| DOI: | 10.1002/anie.201705855 |
| Popis: | Chemoenzymatic and enzymatic cascade reactions enable the synthesis of complex stereocomplementary 1,3,4‐trisubstituted tetrahydroisoquinolines (THIQs) with three chiral centers in a step‐efficient and selective manner without intermediate purification. The cascade employs inexpensive substrates (3‐hydroxybenzaldehyde and pyruvate), and involves a carboligation step, a subsequent transamination, and finally a Pictet–Spengler reaction with a carbonyl cosubstrate. Appropriate selection of the carboligase and transaminase enzymes enabled the biocatalytic formation of (1R,2S)‐metaraminol. Subsequent cyclization catalyzed either enzymatically by a norcoclaurine synthase or chemically by phosphate resulted in opposite stereoselectivities in the products at the C1 position, thus providing access to both orientations of the THIQ C1 substituent. This highlights the importance of selecting from both chemo‐ and biocatalysts for optimal results. |
| Databáze: | OpenAIRE |
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