Regio- and stereoselective aspects in the oxidation of (R) and (S) 4a-methyl-(4,4a,5,6,7,8)-hexahydro-2(3H)naphthalenones in living rats

The bioconversion of (R)-1 and (S)-1 in living rats was studied. The urinary hydroxylated metabolites obtained were identified by using GC-MS and 1H NMR spectroscopy. Oxidation of octalenones (R)-1 and (S)-1 in living rats took place at three sites: positions 6,7 and 8. However, for a given site, this oxidation was highly stereoselective: only one hydroxylated diastereomer was always obtained. With the exception of metabolite 6, the oxidation always occurred in the syn position relatively to the angular methyl group. These results are significantly different from those observed, using “alternative methods”, such as microsomal and microbial biodegradations. These data show that from a stereochemical and a regiochemical viewpoint, “alternative methods” need to be validated by controls in living animals.