Is the formation of R-ibuprofenyl-adenylate the first stereoselective step of chiral inversion?
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-adenylate 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.
Menzel
S
S
Department of Experimental and Clinical Pharmacology, University of Erlangen-Nuernberg, Germany.
Waibel
R
R
Brune
K
K
Geisslinger
G
G
D000818:Animals; D003065:Coenzyme A / Q000378:metabolism; D004952:Esters; D007052:Ibuprofen / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D004952:Esters; D003065:Coenzyme A; D007052:Ibuprofen