Transformation of a monoterpene ketone, piperitenone, and related terpenoids using Mucor piriformis.

Biotransformation of piperitenone (I), 5,5-dimethyl-2-(1-methylethylidene)-cyclohexanone (II), and 2-(1-ethyl-1-propylidene)-5-methylcyclohexanone (III) was studied using a versatile fungal strain, Mucor piriformis. The organism initiates transformation of these compounds by hydroxylation at the allylic positions or at the tertiary carbon. Transformation of piperitenone (I) by this strain yielded 5-hydroxypiperitenone (Ic), 7-hydroxypiperitenone (Id), 7-hydroxypulegone (Ie), 10-hydroxypiperitenone (If), and 4-hydroxypiperitenone (Ig) as metabolites. It was possible to block some of the metabolic activities of the organism through structural modification of piperitenone (I). This was evidenced by the fact that biotransformation of 5,5-dimethyl-2-(1-methylethylidene)-cyclohexanone (II) yielded 5,5-dimethyl-2-(1-hydroxy-1-methylethyl)-2-cyclohexen-1-one (IIb) and 5,5-dimethyl-3-hydroxy-2-(1-methylethylidene)-cyclohexanone (IIa), whereas 2-(1-ethyl-1-propylidene)-5-methylcyclohexanone (III) yielded 6-(1-ethyl-1-propylidene)-5-methyl-2-cyclohexen-1-one (IIIb) and 6-(1-ethyl-1-propylidene)-5-hydroxy-5-methylcyclohexanone (IIIa) as metabolites. Based on the identification of the metabolites, pathways for the biotransformation of I, II, and III have been proposed. The mode of biotransformation of these compounds by M. piriformis also compared to their modes of metabolism in the rat system.