Magnetic Attachment of Lipase Immobilized on Bacteriogenic Iron Oxide Inside a Microtube Reactor for the Kinetic Resolution of Secondary Alcohols

Abstract

A PTFE microtube reactor was constructed with lipase immobilized on magnetized bacteriogenic iron oxide, which was retained inside of the tube by attraction to an external magnet. The reactor was used for the lipase-promoted kinetic resolution of secondary alcohols and gave sufficient catalytic activity, which was maintained during long-term flow over 14 days.

Key words

iron oxide - microreactor - kinetic resolution - lipase - magnetic attachment

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• 25 Typical procedure for construction of the microtube reactor: The tube was placed in a narrow groove cut into a wooden block (ca. 10 cm long) with almost the same width as the tube. One side of the tube (40 cm) was connected to a diaphragm pump via a PEEK connector and BCL/m-BIO-M (2 or 4 mg) was sucked from the other side. BCL/m-BIO-M was retained by the magnetic interaction with an external assembly of neodymium magnets placed at a middle part of the tube. The tube, wooden stick, and the magnets were put on a wire-woven base in a water bath filled with water (30 °C). The tube was then connected to a gas-tight syringe via a PEEK connector, which was filled with alcohol and vinyl acetate in diisopropyl ether, and the syringe was placed on a syringe pump.
• 26 Typical procedure for kinetic resolution of secondary alcohol in the microtube reactor: A gas-tight syringe filled with a solution of the secondary alcohol (0.2 M) and vinyl acetate (0.4 M) in diisopropyl ether was placed on a syringe pump. The solution was fed at a defined flow rate and several drops of the eluent was collected in a sample tube and directly analyzed by HPLC. The enantiomeric excess (ee) values of the ester and unreacted alcohol were obtained by chiral HPLC analysis. The conversion (c) and enantiomeric ratio (E) of kinetic resolution were calculated according to a literature method.²⁷ Kinetic resolution of 1a: The characteristics of the products were consistent with previous data.¹¹ (S)-1a: ¹H NMR (CDCl₃, 600 MHz): δ = 7.39–7.26 (m, 5 H), 4.91 (q, J = 6.6 Hz, 1 H), 1.51 (d, J = 6.6 Hz, 3 H); HPLC [CHIRALCEL OJ-H; hexane/i-PrOH, 99:1; flow rate 0.5 mL/min; UV detection λ = 254 nm]: R_t = 24.4 (S), 29.0 (R) min. (R)-2a: ¹H NMR (CDCl₃, 600 MHz): δ = 7.35–7.27 (m, 5 H), 5.89 (q, J = 6.6 Hz, 1 H), 2.07 (s, 3 H), 1.54 (d, J = 6.6 Hz, 3 H); HPLC [CHIRALCEL OJ-H; hexane/i-PrOH, 99:1; flow rate 0.5 mL/min; UV detection λ = 254 nm]: R_t = 60.0 (R), 64.9 (S) min. Kinetic resolution of 1b. The production of (S)-1b and (R)-2a was confirmed by comparison of the ¹H NMR spectrum of the crude mixture with those of (S)-1b and (R)-2b reported previously.¹¹ HPLC [CHIRALCEL OJ-H; hexane/i-PrOH, 19:1; flow rate 0.6 mL/min, UV detection λ = 254 nm]: R_t = (S)-1b: 22.4 (S), 26.6 (R) min; (R)-2b: 42.3 (R), 56.5 (S) min.
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