No abstract

Both enantiomers of 1,2,3,4‐tetrahydro‐β‐carboline‐1‐carboxylic acid have been prepared by dynamic kinetic resolution of the corresponding ethyl ester (±)‐1. CAL‐B‐catalysed hydrolysis of (±)‐1·HCl in NH4OAc buffer (pH 8.0, 30 °C) provided amino acid (R)‐2·HCl with 98 % ee and 90 % yield in 20 min. The hydrolysis with Alcalase in borate buffer (pH 8.0, 30 °C) showed S selectivity and the product (S)‐2·HCl was obtained with 60 % ee and 66 % yield in 45 h. The absolute configuration of (S)‐2 was determined by TDDFT electronic circular dichroism and optical rotation calculations.

In this study we attempted to describe in a comparative manner the enantioselectivity performance of six different polysaccharide- and two strong cation exchanger-type chiral stationary phases (CSPs) for the resolution of free and N-protected β-carboline derivatives. On commercially available cellulose- or amylose-based CSPs, the enantioseparations were carried out in normal-phase mode by variation of the nature and the concentration of the alcohol modifier in n-hexane as mobile phase. With the application of strong cation exchanger-type CSPs, the enantioseparations were optimized by the variation of methanol-acetonitrile bulk solvent compositions in the presence of various amounts of acid and base additives acting as counter-ions. Detailed thermodynamic investigations revealed that in all cases the enantioseparations observed were enthalpically driven, i.e. the retention and selectivity decreased with increasing temperature. Elution sequences were determined routinely; no general rule was found on polysaccharide-based CSPs, while on the two enantiomeric strong cation exchanger-type CSPs the predicted reversal of the elution sequence could be confirmed on switching from one enantiomeric CSP to the other form.

No 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 %).