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...
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ftpubmed:oai:pubmedcentral.nih.gov:4984410 2023-05-15T13:53:13+02:00 Enzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐β‐carboline Derivatives in Batch and Continuous‐Flow Systems Megyesi, Rita Forró, Enikő Fülöp, Ferenc 2016-03-01 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984410/ http://www.ncbi.nlm.nih.gov/pubmed/27551661 https://doi.org/10.1002/open.201500203 en eng John Wiley and Sons Inc. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984410/ http://www.ncbi.nlm.nih.gov/pubmed/27551661 http://dx.doi.org/10.1002/open.201500203 © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. CC-BY-NC-ND Full Papers Text 2016 ftpubmed https://doi.org/10.1002/open.201500203 2016-08-28T00:10:47Z 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 %). Text Antarc* Antarctica PubMed Central (PMC) ChemistryOpen 5 3 254 260 |
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Full Papers Megyesi, Rita Forró, Enikő Fülöp, Ferenc Enzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐β‐carboline Derivatives in Batch and Continuous‐Flow Systems |
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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 %). |
format |
Text |
author |
Megyesi, Rita Forró, Enikő Fülöp, Ferenc |
author_facet |
Megyesi, Rita Forró, Enikő Fülöp, Ferenc |
author_sort |
Megyesi, Rita |
title |
Enzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐β‐carboline Derivatives in Batch and Continuous‐Flow Systems |
title_short |
Enzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐β‐carboline Derivatives in Batch and Continuous‐Flow Systems |
title_full |
Enzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐β‐carboline Derivatives in Batch and Continuous‐Flow Systems |
title_fullStr |
Enzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐β‐carboline Derivatives in Batch and Continuous‐Flow Systems |
title_full_unstemmed |
Enzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐β‐carboline Derivatives in Batch and Continuous‐Flow Systems |
title_sort |
enzymatic strategy for the resolution of new 1‐hydroxymethyl tetrahydro‐β‐carboline derivatives in batch and continuous‐flow systems |
publisher |
John Wiley and Sons Inc. |
publishDate |
2016 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984410/ http://www.ncbi.nlm.nih.gov/pubmed/27551661 https://doi.org/10.1002/open.201500203 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984410/ http://www.ncbi.nlm.nih.gov/pubmed/27551661 http://dx.doi.org/10.1002/open.201500203 |
op_rights |
© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
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CC-BY-NC-ND |
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https://doi.org/10.1002/open.201500203 |
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