Stereospecific inversion of l-alpha-methylfluorene-2-acetic acid to its d-enantiomer in the dog.
1. After administration of dl-alpha-methylfluorene-2-acetic acid to dogs, the optical rotation of the drug in blood increased with time. Of the total drug in blood, the d-enantiomer increased from 61 to 80% between 3 and 24 h after administration; by 384 h it was 100%. 2. Both l- and d-enantiomers had plasma half-lives and excretion characteristics similar to those of the dl-racemic mixture, indicating that the increase in the proportion of the d-enantiomer was not due to more rapid excretion of the l-enantiomer. 3. Studies of optical rotation and circular dichroism demonstrated that the l-enantiomer was converted to the d-enantiomer in the blood of the dog, but the d-enantiomer remained unchanged. After administration of the l-enantiomer, the d-enantiomer increased from 26 to 71% of the total drug in blood between 0-3 and 2 days after administration; 14 days after dosing, almost all of the drug was present as the d-enantiomer. 4. Isomerization of l-alpha-methylfluorene-2-acetic acid to its d-enantiomer also occurs in rat, monkey and man.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002855:Chromatography, Thin Layer; D002942:Circular Dichroism; D004285:Dogs; D005260:Female; D005449:Fluorenes / Q000378:metabolism*; D006207:Half-Life; D007535:Isomerases / Q000378:metabolism*; D008297:Male; D008968:Molecular Conformation; D009904:Optical Rotation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000085:Acetates; D005449:Fluorenes; D007535:Isomerases