Enantioselective Chromatographic Separation and Lipase Catalyzed Asymmetric Resolution of Biologically Important Chiral Amines

Abstract

Cyanoacetamides are vital synthons in synthetic organic chemistry. However, methods to enantiopure cyanoacetamides have not yet been well explored. In this work, the preparation of cyanoacetamide synthons RS-(1a–4a) or methoxyacetamides RS-(1b–4b) in enantiopure/enriched form was investigated. Compounds S-1, S-2, R-1b, R-1a, andR-2b were prepared in enantiopure form (ee > 99%) while compounds S-4, R-2a, and R-4a were achieved in ee 9%, 80%, and 76%, respectively. Many baselines enantioselective HPLC separations of amines 1–4, their cyanoacetamides (1a–4a), and methoxyacetamides (1b–4b) were achieved by utilizing diverse mobile-phase compositions and two cellulose-based CSPs (ODH® and LUX-3® columns). Such enantioselective HPLC separations were used to monitor the lipase-catalyzed kinetic resolution of amines RS-(1–4).

Immobilization of Lipase B from Candida antarctica on Magnetic Nanoparticles Enhances Its Selectivity in Kinetic Resolutions of Chiral Amines with Several Acylating Agents

“…After the removal of the solvent via vacuum rotary evaporation, the residue was purified with vacuum distillation to yield 2-ethoxyacetic acid as a colorless oil. Yield = 76%; Bp = 90 • C (34 Torr); TLC: Rf = 0.29 (CH 2 Cl 2 :MeOH = 10:1); 1 H-NMR (500 MHz, chloroform-d 3 , δ ppm): 8.92 (s, 1H), 4.15 (s, 2H), 3.65 (q, J = 7.0 Hz, 1H), 1.29 (t, J = 7.0 Hz, 2H); 13 2-Ethoxyacetic acid (28 g, 0.272 mol, 25.4 mL) and p-toluenesulfonic acid (0.92 g, 5.4 mmol) were dissolved in 2-propanol (150 mL), and the resulting mixture was refluxed for 32 h. During distilling off the excess alcohol at atmospheric pressure, an additional 100 mL of 2-propanol was added dropwise to perfectly remove the formed water via azeotropic distillation. The residual crude ester was purified via vacuum distillation to give pure isopropyl 2-ethoxyacetate as a colorless oil.…”

“…Yield: 15.1 g (81%); bp = 70 • C (38 Torr); TLC: Rf = 0.78 (hexane:EtOAc = 7:3); 1 H-NMR (500 MHz, chloroform-d 3 , δ ppm): δ 5.11 (m, 1H), 4.04 (s, 2H), 3.60 (q, J = 7.0 Hz, 2H), 1.30-1.23 (d+t, 9H); 13…”

“…Yield: 29 mg, 31 % (ee = 99.5%, by GC); 1 H NMR (500 MHz, chloroform-d 3 , δ ppm): 8.62 (s, 1H), 4.00 (p, J = 7.0 Hz, 2H), 3.38 (s, 2H), 1.54-1.43 (m, 2H), 1.39-1.26 (m, 6H), 1.20 (d, J = 6.6 Hz, 2H), 0.91 (t, J = 6.5 Hz, 3H); 13 The U-shape MNP reactor system (Figure 1), similar to its nonthermostatted predecessor [9], was designed using AutoCAD (2020 student version) and printed with a Rankfor100 3D printer (CEI Conrad Electronic International, Ltd., New Territories, Hong Kong). In this study, we used neodymium disc magnets, 4 mm × 2 mm, N35 (Euromagnet Ltd., Budapest, Hungary) as permanent magnets and a polytetrafluoroethylene (PTFE) tube with ID 1.50 mm as the reactor body and connection parts.…”

“…However, like every other free enzyme, it can have several limitations, such as instability, nonreusability, and sensitivity to several reactants, which immobilization can circumvent [6]. The immobilized forms of this versatile biocatalyst have been used for the KR of chiral alcohols [7][8][9][10], azolides [11], and amines [12][13][14][15][16][17].…”

Separation Methods in Biomedical Analysis, a Booming Field

“…Many baseline enantioselective HPLC separations of amines 1-4, their cyanoacetamides (1a-4a), and methoxyacetamides (1b-4b) were achieved by utilizing diverse mobile-phase compositions and two cellulose-based CSPs (ODH ® and LUX-3 ® columns). Such enantioselective HPLC separations were used to monitor the lipase-catalyzed kinetic resolution of amines RS-(1-4) [29].…”