title: Comparison of the efficiency of various methods for the synthesis of models of metabolites: example of 4a-methylhexahydronaphtalenones.
abstract: In order to examine the biotransformations of xenobiotics, it is essential to realize studies of metabolism of drugs in living animals. It is generally difficult to extract quantitatively the metabolites from biological media or excreta. Alternative methods have then been developed. Application of such techniques to 4a-methylhexahydronaphthalenones, which constitute starting material for the stereospecific synthesis of terpenoids or steroids, is particularly demonstrative. By biosynthetical ways, it was not possible to access with good yields to all the metabolites obtained in vivo. A novel methodology, based on the use of a manganoporphyrin catalyst, allowed to synthesize large amounts of several models of metabolites corresponding to those which had been isolated in living rats. Only one of the metabolites obtained in vivo could not be synthesized by this biomimetic system. This proved that alternative methods are precious to obtain models with good yields, but need to be validated by controls in living animals.
authors.affiliation: Laboratoire de pharmacochimie, département de chimie organique pharmaceutique, faculté de médecine et de pharmacie de Rouen, 22, boulevard Gambetta, 76183 Rouen Cedex 1, France.
authors.forename: François
authors.initials: F
authors.lastname: Estour
authors.forename: Sabine
authors.initials: S
authors.lastname: Ménager
authors.forename: Bernardin
authors.initials: B
authors.lastname: Akagah
authors.forename: Olivier
authors.initials: O
authors.lastname: Lafont
mesh_terms: D000818:Animals; D001711:Biotransformation / Q000502:physiology; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000378:metabolism*; D010084:Oxidation-Reduction; D013678:Technology, Pharmaceutical / Q000379:methods*; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D009281:Naphthalenes; D015262:Xenobiotics