REGIOSELECTIVE AND STEREOSELECTIVE ASPECTS IN THE OXIDATION OF METHYL-(4,4A,5,6,7,8)-HEXAHYDRO-2(3H)NAPHTHALENONE AND METHYL-(4,4A,5,6,7,8)-HEXAHYDRO-2(3H)NAPHTHALENONE IN LIVING RATS

The bioconversion of (R)-1 and (S)-1 in living rats was studied. The u rinary hydroxylated metabolites obtained were identified by using GC-M S and H-1 NMR spectroscopy. Oxidation of octalenones (R)-1 and (S)-1 i n 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 relati vely to the angular methyl group. These results are significantly diff erent from those observed, using ''alternative methods'', such as micr osomal and microbial biodegradations. These data show that from a ster eochemical and a regiochemical viewpoint, ''alternative methods'' need to be validated by controls in living animals. (C) 1997 Elsevier Scie nce Ltd. All rights reserved.