Enzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐β‐carboline Derivatives in Batch and Continuous‐Flow Systems
Abstract 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‐...
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crwiley:10.1002/open.201500203 2024-06-02T07:57:06+00:00 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 Hungarian Research Foundation 2016 http://dx.doi.org/10.1002/open.201500203 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fopen.201500203 http://onlinelibrary.wiley.com/wol1/doi/10.1002/open.201500203/fullpdf en eng Wiley http://creativecommons.org/licenses/by-nc-nd/4.0/ ChemistryOpen volume 5, issue 3, page 254-260 ISSN 2191-1363 2191-1363 journal-article 2016 crwiley https://doi.org/10.1002/open.201500203 2024-05-03T11:10:59Z Abstract 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 %). Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library ChemistryOpen 5 3 254 260 |
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Abstract 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 %). |
author2 |
Hungarian Research Foundation |
format |
Article in Journal/Newspaper |
author |
Megyesi, Rita Forró, Enikő Fülöp, Ferenc |
spellingShingle |
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 |
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 |
Wiley |
publishDate |
2016 |
url |
http://dx.doi.org/10.1002/open.201500203 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fopen.201500203 http://onlinelibrary.wiley.com/wol1/doi/10.1002/open.201500203/fullpdf |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
ChemistryOpen volume 5, issue 3, page 254-260 ISSN 2191-1363 2191-1363 |
op_rights |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
op_doi |
https://doi.org/10.1002/open.201500203 |
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ChemistryOpen |
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5 |
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3 |
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254 |
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260 |
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1800738663528660992 |