An efficient system for the asymmetric acylation of (R,S)-3-n-butylphthalide catalyzed by novozyme 435.
Novozyme 435 could be a highly efficient catalyst in the asymmetric acylation of (R,S)-3-n-butylphthalide in tetrahydrofuran-hexane solvents. The effect of various reaction parameters such as agitation velocity, water content, mixed media, temperature, concentration of Novozyme 435, molar ratio of acetic anhydride to (R,S)-3-n-butylphthalide, reaction time, enantiomeric excess of substrate (ee(S)), enantiomeric excess of product (ee(P)), and enantioselective ratio (E) were studied. Tetrahydrofuran markedly improved (R,S)-3-n-butylphthalide conversion, enantiomeric excess of remaining 3-n-butylphthalide, and enantiomeric ratio. The optimum media were 50% (v/v) tetrahydrofuran and 50% (v/v) hexane. Other ideal reaction conditions were an agitation velocity of 150 rpm, 0.4% (v/v) water content, temperature of 30 °C, 8 mg/mL dosage of Novozyme 435, 8:1 (0.4 mmol: 0.05 mmol) molar ratio of acetic anhydride to (R,S)-3-n-butylphthalide, and a reaction time of 48 hr. Under the optimum conditions, 96.4% ee(S) and 49.3% conversion of (R,S)-3-n-butylphthalide were achieved. In addition, enantiomeric excess of the product was above 98.0%.
School of Chemical Engineering of Guizhou University, Caijiaguan, Guiyang, Guizhou Province, P.R. China.
Cuiqin
C
Li
Laping
L
He
Baoquan
B
Qiu
Bing
B
Gao
D000215:Acylation; D001572:Benzofurans / Q000737:chemistry / Q000378:metabolism*; D002175:Candida / Q000201:enzymology*; D002384:Catalysis; D004800:Enzymes, Immobilized / Q000378:metabolism*; D005656:Fungal Proteins; D005663:Furans / Q000737:chemistry; D008049:Lipase / Q000378:metabolism*; D014867:Water / Q000737:chemistry
D001572:Benzofurans; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D005663:Furans; D014867:Water; C018674:tetrahydrofuran; C027125:3-n-butylphthalide; C093667:Novozyme 435; D008049:Lipase