IS THE FORMATION OF R-IBUPROFENYL-ADENYLATE THE FIRST STEREOSELECTIVE STEP OF CHIRAL INVERSION

被引：42

作者：

MENZEL, S ^{[1
]}

WAIBEL, R ^{[1
]}

BRUNE, K ^{[1
]}

GEISSLINGER, G ^{[1
]}

机构：

[1] UNIV ERLANGEN NURNBERG,DEPT PHARMACEUT CHEM,D-91054 ERLANGEN,GERMANY

来源：

BIOCHEMICAL PHARMACOLOGY | 1994年 / 48卷 / 05期

关键词：

2-ARYLPROPIONIC ACIDS; STEREOSELECTIVITY; MECHANISM OF INVERSION; INTERMEDIATES; ACYL ADENYLATES; COENZYME A THIOESTER FORMATION;

D O I：

10.1016/0006-2952(94)90380-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Coenzyme A thioester formation is reported to be the first step of chiral inversion of R-ibuprofen. In order to investigate the mechanism of this reaction adenylate derivatives of the ibuprofen enantiomers were synthesized chemically. R- and S-ibuprofenyl-adenylates as well as free acids were incubated with rat liver mitochondria in the presence of coenzyme A, MgCl2 with or without ATP. The optical antipodes formed by inversion and the coenzyme A thioester derivatives of both enantiomers were found after incubation of both R- or S-ibuprofenyl-adenlyate and R-ibuprofen, By contrast, after incubation with S-ibuprofen neither R-enantiomer nor coenzyme A thioesters were detected. These experiments suggest that the formation of R-ibuprofenyl-adenylate may be the first stereoselective step of chiral inversion.

引用

页码：1056 / 1058

页数：3

共 14 条

[1]

BERG P, 1958, J BIOL CHEM, V233, P608

[2]

BERG P, 1956, J BIOL CHEM, V222, P991

[3] THE METABOLIC CHIRAL INVERSION AND DISPOSITIONAL ENANTIOSELECTIVITY OF THE 2-ARYLPROPIONIC ACIDS AND THEIR BIOLOGICAL CONSEQUENCES [J].

CALDWELL, J ;

HUTT, AJ ;

FOURNELGIGLEUX, S .

BIOCHEMICAL PHARMACOLOGY, 1988, 37 (01) :105-114

[4] ENANTIOSPECIFIC FORMATION OF FENOPROFEN COENZYME-A THIOESTER INVITRO [J].

KNIGHTS, KM ;

DREW, R ;

MEFFIN, PJ .

BIOCHEMICAL PHARMACOLOGY, 1988, 37 (19) :3539-3542

[5] CHIRAL INVERSION OF 2-ARYLPROPIONIC ACID NONSTEROIDAL ANTIINFLAMMATORY DRUGS .2. RACEMIZATION AND HYDROLYSIS OF (R)-IBUPROFEN-COA AND (S)-IBUPROFEN-COA THIOESTERS [J].

KNIHINICKI, RD ;

DAY, RO ;

WILLIAMS, KM .

BIOCHEMICAL PHARMACOLOGY, 1991, 42 (10) :1905-1911

[6]

MAO LF, 1992, J BIOL CHEM, V267, P3243

[7] STEREOSELECTIVE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF KETOPROFEN, IBUPROFEN AND FENOPROFEN IN PLASMA USING A CHIRAL ALPHA-1-ACID GLYCOPROTEIN COLUMN [J].

MENZELSOGLOWEK, S ;

GEISSLINGER, G ;

BRUNE, K .

JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1990, 532 (02) :295-303

[8] INFLUENCE OF PALMITATE AND BENZOATE ON THE UNIDIRECTIONAL CHIRAL INVERSION OF IBUPROFEN IN ISOLATED RAT HEPATOCYTES [J].

MULLER, S ;

MAYER, JM ;

ETTER, JC ;

TESTA, B .

BIOCHEMICAL PHARMACOLOGY, 1992, 44 (07) :1468-1470

[9]

NAKAMURA Y, 1981, J PHARMACOBIO-DYNAM, V4, pS1

[10] METABOLIC CHIRAL INVERSION OF FLURBIPROFEN-COA INVITRO [J].

PORUBEK, DJ ;

SANINS, SM ;

STEPHENS, JR ;

GRILLO, MP ;

KAISER, DG ;

HALSTEAD, GW ;

ADAMS, WJ ;

BAILLIE, TA .

BIOCHEMICAL PHARMACOLOGY, 1991, 42 (01) :R1-R4

← 1 2 →