[Porphyrin catalysts: a tool for preparation of metabolite models].
The porphyrin complexes of manganese catalysts are biomimetic catalysts whose structural analogy with the active site of cytochrome P-450 enzymes can be used to obtain synthetic models of therapeutic agent metabolites. Mn(TDCOO)Cl, a second generation porphyrin, has proven robust enout to be used for scaled-up production in the presence of hydrogen peroxide and imidazole. For this purpose, an improvement in substrate oxidation was obtained by adjunction of formic acid to the reaction medium which preserved the cocatalyst and the catalyst. It was shown that addition of acid played an active role in the oxidation process. After this optimization, the system was used to oxidate the two enantiomers of methyloctalone, an essential chiral intermediate in the synthesis of terpenoids and steroids. The efficacy of this biomimetic method for the preparation of large amounts of oxidized chiral synthons was better than obtained with biological ex vivo pathways.
Estour
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Laboratoire de Pharmacochimie, Département de Chimie organique pharmaceutique, Faculté de Médecine et de Pharmacie de Rouen, 22, boulevard Gambetta, F76183 Rouen Cedex 1.
Akagah
B
B
Ségrestaa
J
J
Vérité
P
P
Ménager
S
S
Lafont
O
O
D000818:Animals; D001711:Biotransformation; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D018716:Molecular Mimicry; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011166:Porphyrins / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D011166:Porphyrins; D003577:Cytochrome P-450 Enzyme System