Novozyme 435-Catalyzed Asymmetric Acylation of (R, S)-3-n-Butylphthalide in Hexane

Abstract

The asymmetric acylation of (R, S)-3-n-butylphthalide could be efficiently catalyzed by Novozyme 435. The effect of various reaction parameters such as water activity, temperature, molar ratio of acetic anhydride to (R, S)-3-n-butylphthalide, and reaction time on the asymmetric acylation were studied. The optimums of the reaction parameters were water activity 0.62, temperature 30°C, molar ratio of acetic anhydride to (R, S)-3-n-butylphthalide 8:1, and reaction time 48 h, respectively. Under the optimum conditions, enantiopure 3-n-butylphthalide with an optical purity of 95.7% enantiomeric excess and 49.1% yield could be obtained. Furthermore, the enantiomeric excess of product was over 98%.

Keywords:

• Asymmetric acylation
• 3-n-Butylphthalide
• Molar ratio
• Novozyme 435
• Temperature
• Water activity

ACKNOWLEDGMENTS

We owe thanks to Shijiazhuang Pharma group 3-n-butylphthalide pharmaceutical Co., Ltd, China for their kind gift of (R, S)-3-n-butylphthalide, and Novo Nordisk, Bagsvard, Denmark for their kind gift of Novozyme 435.

Manuscript 7582