Enzymatic Strategy for the Resolution of New 1-Hydroxymethyl Tetrahydro-β-carboline Derivatives in Batch and Continuous-Flow Systems
Many alkaloids containing a tetrahydro-β-carboline skeleton have well-known therapeutic effects, leading to increased interest in the synthesis of these natural products. Enantiomers of N-Boc-protected 1-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline [(±)-7], 1-hydroxymethyl-6-methoxy-1,2,3,4-tetrahyd...
| Published in: | ChemistryOpen |
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| Main Authors: | , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
Wiley
2016
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| Subjects: | |
| Online Access: | http://publicatio.bibl.u-szeged.hu/9901/ http://publicatio.bibl.u-szeged.hu/9901/1/megyesi_chemopen.pdf https://doi.org/10.1002/open.201500203 |
| Summary: | Many alkaloids containing a tetrahydro-β-carboline skeleton have well-known therapeutic effects, leading to increased interest in the synthesis of these natural products. Enantiomers of N-Boc-protected 1-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline [(±)-7], 1-hydroxymethyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline [(±)-8], and 1-hydroxymethyl-6-fluoro-1,2,3,4-tetrahydro-β-carboline [(±)-9] were prepared through enzymecatalyzed asymmetric acylation of their primary hydroxyl group. The preliminary experiments were performed in a continuous-flow system, while the preparative-scale resolutions were done as batch reactions. Excellent enantioselectivities (E>200) were obtained with Candida antarctica lipase B (CAL-B) and acetic anhydride in toluene at 60°C. The recovered alcohols and the produced esters were obtained with high enantiomeric excess values (ee≥96%). The O-acylated enantiomers [(S)-10-(S)-12)] were transformed into the corresponding amino alcohols [(S)-7-(S)-9)] with methanolysis. Microwave-assisted Boc removals were also performed and resulted in the corresponding compounds (R)-4-(R)-6 and (S)-4-(S)-6 without a drop in the enantiomeric excess values (ee≥96%). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
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