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‐...
Published in: | ChemistryOpen |
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Main Authors: | , , |
Other Authors: | |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Wiley
2016
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Subjects: | |
Online Access: | 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 |
Summary: | 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 %). |
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