A facile enzymatic process for the preparation of (s)-Naproxen ester prodrug in organic solvents

被引:38
作者
Chang, CS [1 ]
Tsai, SW [1 ]
机构
[1] NATL CHENG KUNG UNIV,DEPT CHEM ENGN,TAINAN 70101,TAIWAN
关键词
prodrug; lipase; (s)-naproxen ester; esterification;
D O I
10.1016/S0141-0229(96)00222-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A facile enzymatic synthesis process has been developed to directly prepare the 4-morpholinoethyl ester prodrug of (s)-Naproxen from racemic Naproxen using lipases as the biocatalysts in the organic solvent. With the careful selection of lipase (Lipase MY) and reaction medium (cyclohenane), a high enantiomeric ratio of 136 for the enzyme was obtained. A Ping-Pong Bi Bi mechanism with competitive inhibition by the alcohol was illustrated from the variation of initial rates with substrate concentrations. (C) 1997 by Elsevier Science Inc.
引用
收藏
页码:635 / 639
页数:5
相关论文
共 17 条
[1]   GLYCOLAMIDE ESTERS AS A NOVEL BIOLABILE PRODRUG TYPE FOR NON-STEROIDAL ANTI-INFLAMMATORY CARBOXYLIC-ACID DRUGS [J].
BUNDGAARD, H ;
NIELSEN, NM .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1988, 43 (1-2) :101-110
[2]   GENERAL-ASPECTS AND OPTIMIZATION OF ENANTIOSELECTIVE BIOCATALYSIS IN ORGANIC-SOLVENTS - THE USE OF LIPASES [J].
CHEN, CS ;
SIH, CJ .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1989, 28 (06) :695-707
[3]   MACROMOLECULAR PRODRUGS .14. ABSORPTION CHARACTERISTICS OF NAPROXEN AFTER ORAL-ADMINISTRATION OF A DEXTRAN T-70-NAPROXEN ESTER PRODRUG IN PIGS [J].
HARBOE, E ;
LARSEN, C ;
JOHANSEN, M ;
OLESEN, HP .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1989, 53 (02) :157-165
[4]   MACROMOLECULAR PRODRUGS .15. COLON-TARGETED DELIVERY - BIOAVAILABILITY OF NAPROXEN FROM ORALLY-ADMINISTERED DEXTRAN NAPROXEN ESTER PRODRUGS VARYING IN MOLECULAR-SIZE IN THE PIG [J].
HARBOE, E ;
LARSEN, C ;
JOHANSEN, M ;
OLESEN, HP .
PHARMACEUTICAL RESEARCH, 1989, 6 (11) :919-923
[5]  
HOLMBERG E, 1992, BIOCATALYSIS, V5, P289
[6]   MACROMOLECULAR PRODRUGS .16. COLON-TARGETED DELIVERY - COMPARISON OF THE RATE OF RELEASE OF NAPROXEN FROM DEXTRAN ESTER PRODRUGS IN HOMOGENATES OF VARIOUS SEGMENTS OF THE PIG GASTROINTESTINAL (GI) TRACT [J].
LARSEN, C ;
HARBOE, E ;
JOHANSEN, M ;
OLESEN, HP .
PHARMACEUTICAL RESEARCH, 1989, 6 (12) :995-999
[7]   GLYCOLAMIDE ESTERS AS BIOLABILE PRODRUGS OF CARBOXYLIC-ACID AGENTS - SYNTHESIS, STABILITY, BIOCONVERSION, AND PHYSICOCHEMICAL PROPERTIES [J].
NIELSEN, NM ;
BUNDGAARD, H .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1988, 77 (04) :285-298
[8]   SUBSTRATE STRUCTURE AND SOLVENT HYDROPHOBICITY CONTROL LIPASE CATALYSIS AND ENANTIOSELECTIVITY IN ORGANIC MEDIA [J].
PARIDA, S ;
DORDICK, JS .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (06) :2253-2259
[9]  
RANUCCI E, 1994, J BIOMAT SCI-POLYM E, V6, P141
[10]   ESTER AND AMIDE PRODRUGS OF IBUPROFEN AND NAPROXEN - SYNTHESIS, ANTIINFLAMMATORY ACTIVITY, AND GASTROINTESTINAL TOXICITY [J].
SHANBHAG, VR ;
CRIDER, AM ;
GOKHALE, R ;
HARPALANI, A ;
DICK, RM .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1992, 81 (02) :149-154