A 2-PROPANOL TREATMENT INCREASES THE ENANTIOSELECTIVITY OF CANDIDA-RUGOSA LIPASE TOWARD ESTERS OF CHIRAL CARBOXYLIC-ACIDS

被引:148
作者
COLTON, IJ [1 ]
AHMED, SN [1 ]
KAZLAUSKAS, RJ [1 ]
机构
[1] MCGILL UNIV, DEPT CHEM, MONTREAL, PQ H3A 2K6, CANADA
关键词
D O I
10.1021/jo00106a036
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Crude lipase from Candida rugosa (CRL) is a poorly to moderately enantioselective catalyst for the hydrolysis of esters of 2-substituted carboxylic acids such as 2-arylpropanoic acids (E = 4-10) and 2-(aryloxy)propanoic acids (E = 2-17). Previous workers converted CRL into a high enantioselectivity form using a four-step purification procedure that included an organic solvent treatment. In this paper we report a simple 2-propanol treatment that converts crude CRL to the high enantioselectivity form. Dissolving crude commercial CRL in 50% 2-propanol followed by dialysis to remove 2-propanol increased the total activity by a factor of 1.2-1.6 and the enantioselectivity toward seven carboxylic acids by a factor of 2.3 to >25. We demonstrated synthetic use of this 2-propanol-treated CRL by resolving 10 g of methyl 2-(4-chlorophenoxy)propionate (3-methyl ester), yielding 2.8 g of product acid (93.1% ee R, a serum cholesterol-lowering compound) and 4.7 g of recovered ester (94.4% ee S), corresponding to an enantiomeric ratio of 100 for the resolution. Recent X-ray crystal structures identified two conformational forms of CRL-open and closed. We suggest that the 2-propanol treatment may increase the activity and enantioselectivity by converting the closed form of CRL to the open form.
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页码:212 / 217
页数:6
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