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.
引用
收藏
页码:212 / 217
页数:6
相关论文
共 53 条
  • [1] ENANTIOSELECTIVITY OF CANDIDA-RUGOSA LIPASE TOWARD CARBOXYLIC-ACIDS - A PREDICTIVE RULE FROM SUBSTRATE MAPPING AND X-RAY CRYSTALLOGRAPHY
    AHMED, SN
    KAZLAUSKAS, RJ
    MORINVILLE, AH
    GROCHULSKI, P
    SCHRAG, JD
    CYGLER, M
    [J]. BIOCATALYSIS, 1994, 9 (1-4): : 209 - 225
  • [2] ENANTIOSELECTIVITY OF LIPASE-CATALYZED HYDROLYSIS OF SOME 2-CHLOROETHYL 2-ARYLPROPANOATES STUDIED BY CHIRAL REVERSED-PHASE LIQUID-CHROMATOGRAPHY
    ALLENMARK, S
    OHLSSON, A
    [J]. CHIRALITY, 1992, 4 (02) : 98 - 102
  • [3] IMMUNIZATION OF LIPASE AGAINST ACETALDEHYDE EMERGING IN ACYL TRANSFER-REACTIONS FROM VINYL-ACETATE
    BERGER, B
    FABER, K
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1991, (17) : 1198 - 1200
  • [4] STEREOSPECIFICITY OF THE CHLORIDE-ION CHANNEL - THE ACTION OF CHIRAL CLOFIBRIC ACID ANALOGS
    BETTONI, G
    LOIODICE, F
    TORTORELLA, V
    CONTECAMERINO, D
    MAMBRINI, M
    FERRANNINI, E
    BRYANT, SH
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (08) : 1267 - 1270
  • [5] CHIRAL ALPHA-SUBSTITUTED ALPHA-ARYLOXY ACETIC-ACIDS - SYNTHESIS, ABSOLUTE-CONFIGURATION, CHEMICAL RESOLUTION, AND DIRECT SEPARATION BY HPLC
    BETTONI, G
    FERORELLI, S
    LOIODICE, F
    TANGARI, N
    TORTORELLA, V
    GASPARRINI, F
    MISITI, D
    VILLANI, C
    [J]. CHIRALITY, 1992, 4 (03) : 193 - 203
  • [6] THE ESTERASE PROFILE OF A LIPASE FROM CANDIDA-CYLINDRACEA
    BRAHIMIHORN, MC
    GUGLIELMINO, ML
    ELLING, L
    SPARROW, LG
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1990, 1042 (01) : 51 - 54
  • [7] BROOK MA, 1983, SYNTHESIS-STUTTGART, P201
  • [9] CHAN ASC, 1993, CHEMTECH, V23, P46
  • [10] QUANTITATIVE-ANALYSES OF BIOCHEMICAL KINETIC RESOLUTIONS OF ENANTIOMERS
    CHEN, CS
    FUJIMOTO, Y
    GIRDAUKAS, G
    SIH, CJ
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1982, 104 (25) : 7294 - 7299