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: | Text |
| Language: | English |
| Published: |
John Wiley and Sons Inc.
2016
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| Subjects: | |
| Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984410/ http://www.ncbi.nlm.nih.gov/pubmed/27551661 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 %). |
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