Novozyme 435-Catalyzed Efficient Acylation of 3-n-Butylphthalide in Organic Medium

Abstract

Novozyme 435 could catalyze efficient acylation of 3-n-butylphthalide in organic medium. The conversion of 3-n-butylphthalide increased with the increase of hydrophobicity of solvent below that of hexane. The more available solvent was hexane. Salt hydride could control fixed water activity. The optimum water activity was 0.62. And the optimum of reaction time, velocity of agitation, dosage of Novozyme 435 and acetic anhydride to 3-n-butylphtrhalide molar ratio were 48 hours, 150 rpm, 8 mg/mL and 8:1, respectively. The conversion of 48.9% could be obtained at a water activity of 0.62 in hexane. Furthermore, Novozyme 435 had an enantioselective acylation of racemic 3-n-butylphthalide by original analysis.

Keywords:

• Acylation
• 3-n-butylphthalide
• Novozyme 435
• Organic solvent
• Salt hydrate
• Water activity

ACKNOWLEDGMENTS

We thank Shijiazhuang Pharma group 3-n-butylphthalide pharmaceutical Co., Ltd, China for their gift of 3-n-butylphthalide and Amano Enzyme Inc. for their kind gifts of PS, PS-C, AK and AY. We also thank Ministry of Education, P.R.China for financial supports in the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, IRT0532) and the financial supports of the National “973” plan (2003CB716008).