Open AccessEnzymatic Strategy for the Resolution of New 1‐Hydroxymethyl Tetrahydro‐ β ‐carboline Derivatives in Batch and Continuous‐Flow Systems
Author(s) -
Megyesi Rita,
Forró Enikő,
Fülöp Ferenc
Publication year - 2016
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201500203
Subject(s) - hydroxymethyl , candida antarctica , chemistry , enantiomer , acetic anhydride , acylation , lipase , acetic acid , kinetic resolution , toluene , enantiomeric excess , stereochemistry , organic chemistry , enantioselective synthesis , enzyme , catalysis
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 %).