Method for splitting 2-phenylpropionic acid enantiomer by catalyzing esterification of Novozym 435 lipase

Abstract

The invention relates to a novel chiral splitting method for obtaining an enantiomer of (R)-2-phenylpropionic acid, which belongs to the technical field of biochemical splitting of chiral compounds. By using the stereoselectivity of Novozym 435, the catalytic esterification of a 2-phenylpropionic acid enantiomer in (S)-2-phenylpropionic acid is carried out with high catalytic efficiency to synthesize (S)-2-n-hexyl phenylpropionate, the remaining unreacted substrate is high optical purity (R)-2-phenylpropionic acid, the substrate conversion rate is 97.23%, the enantiomeric excess value is 89.20%, and the target enantiomer yield is 5.24 %. Compared with other methods, the method has the advantages of simple reaction system, high reaction concentration, fast reaction rate, high optical purityof target products, environmental protection, and simple post-treatment.

Description

technical field

[0001] The invention belongs to the separation of chiral compounds by biological methods, and is a kind of stereoselective catalytic esterification of racemic 2-phenylpropionic acid enantiomers using immobilized lipase Novozym 435 to obtain single configuration 2-phenylpropionic acid pairs Enantiomer method. Using Novozym 435 lipase to selectively catalyze the esterification of racemic 2-phenylpropionate to single-configuration n-hexyl (S)-2-phenylpropionate to obtain (R)-2- Phenylpropionic acid. Background technique

[0002] 2-Phenylpropionic acid (2-Phenylpropionic acid), also known as α-phenylpropionic acid, is the simplest structure of arylpropionic acid substances, and is the intermediate for the synthesis of arylpropionic acid anti-inflammatory analgesics and fine chemical products body, and are widely used in the synthesis of medicines, spices and pesticides. 2-Phenylpropionic acid, as an important drug synthesis intermediate, can be used to synthes...

Examples

Embodiment 1

[0014] Add 100 mmol / L 2-phenylpropionic acid and 140 mmol / L n-hexanol, 100 mg Novozym435 lipase into 2 mL n-hexane; heat the reaction at 400 rpm and 50°C in a 25 mL reaction tube 60 min. At this time, the substrate conversion rate was 97.33%, the enantiomer excess value of the remaining 2-phenylpropionic acid enantiomer was 87.41%, and the target enantiomer yield was 5.01%.

Embodiment 2

[0016] Add 100 mmol / L 2-phenylpropionic acid and 200 mmol / L n-hexanol, 300 mg Novozym435 lipase into 2 mL n-hexane organic solvent; in a 25 mL reaction tube at 400 rpm, 50 °C Heat the reaction for 45 min. At this point, the substrate conversion rate was 97.23%, the enantiomer excess value of the remaining 2-phenylpropionic acid enantiomer was 89.20%, and the yield of the target enantiomer was 5.24%.

Embodiment 3

[0018] Add 10 mmol / L 2-phenylpropionic acid, 140 mmol / L n-hexanol, and 60 mg of Novozym435 lipase into 2 mL of n-hexane organic solvent; heat in a 25 mL reaction tube at 400 rpm and 50 °C React for 140 min. At this time, the substrate conversion rate was 86.73%, the enantiomer excess value of the remaining 2-phenylpropionic acid enantiomer was 86.74%, and the yield of the target enantiomer was 24.77%.

technical field

[0001] The invention belongs to the separation of chiral compounds by biological methods, and is a kind of stereoselective catalytic esterification of racemic 2-phenylpropionic acid enantiomers using immobilized lipase Novozym 435 to obtain single configuration 2-phenylpropionic acid pairs Enantiomer method. Using Novozym 435 lipase to selectively catalyze the esterification of racemic 2-phenylpropionate to single-configuration n-hexyl (S)-2-phenylpropionate to obtain (R)-2- Phenylpropionic acid. Background technique

[0002] 2-Phenylpropionic acid (2-Phenylpropionic acid), also known as α-phenylpropionic acid, is the simplest structure of arylpropionic acid substances, and is the intermediate for the synthesis of arylpropionic acid anti-inflammatory analgesics and fine chemical products body, and are widely used in the synthesis of medicines, spices and pesticides. 2-Phenylpropionic acid, as an important drug synthesis intermediate, can be used to synthes...

Examples

Embodiment 1

[0014] Add 100 mmol / L 2-phenylpropionic acid and 140 mmol / L n-hexanol, 100 mg Novozym435 lipase into 2 mL n-hexane; heat the reaction at 400 rpm and 50°C in a 25 mL reaction tube 60 min. At this time, the substrate conversion rate was 97.33%, the enantiomer excess value of the remaining 2-phenylpropionic acid enantiomer was 87.41%, and the target enantiomer yield was 5.01%.

Embodiment 2

[0016] Add 100 mmol / L 2-phenylpropionic acid and 200 mmol / L n-hexanol, 300 mg Novozym435 lipase into 2 mL n-hexane organic solvent; in a 25 mL reaction tube at 400 rpm, 50 °C Heat the reaction for 45 min. At this point, the substrate conversion rate was 97.23%, the enantiomer excess value of the remaining 2-phenylpropionic acid enantiomer was 89.20%, and the yield of the target enantiomer was 5.24%.

Embodiment 3

[0018] Add 10 mmol / L 2-phenylpropionic acid, 140 mmol / L n-hexanol, and 60 mg of Novozym435 lipase into 2 mL of n-hexane organic solvent; heat in a 25 mL reaction tube at 400 rpm and 50 °C React for 140 min. At this time, the substrate conversion rate was 86.73%, the enantiomer excess value of the remaining 2-phenylpropionic acid enantiomer was 86.74%, and the yield of the target enantiomer was 24.77%.