Microbial models of mammalian metabolism. O-Dealkylation of 10,11-dimethoxyaporphine

Abstract

Microbial transformations of 10,11-dimethoxyaporphine were studied to determine the potential of microorganisms to produce monomethoxyaporphines. Ten microorganisms were identified as being capable of yielding apocodeine and/or isoapocodeine as the major metabolite in 24 and 20% yield, respectively. Cunninghamella blakesleeana (ATCC 9245) converted 10,11-dimethoxyaporphine quantitatively into isapocodeine. O-Dealkylation of this aporphine system is a facile microbial transformation, and the 10-methoxyl group is more susceptible to metabolic cleavage than the sterically hindered 11-methoxyl group. Selectivity in O-dealkylation may be accomplished with different microorganisms. This is the first report dealing with the microbial transformation of an aporphine system.

Microbial Models of Mammalian Metabolism

“…Our findings with C. blakesleeana and C. echinulata (115), which produced mostly isoapocodeine, support the result of Boothroyd et al (113) that selective 0-dealkylation may be achieved with different microorganisms.…”

“…We have conducted several experiments on microbial 0-dealkylations, predominantly with methoxylated aporphine and benzylisoquinoline derivatives (115). Cannon et al (116) studied the synthesis of the isomeric monomethyl metabolites of apomorphine and metabolism of apomorphine in a catechol-0-methyltransferase liver preparation.…”

“…We have also been studying the microbial metabolism of the drug papaverine (IV) (115). Papaverine has been used in treating cerebral and peripheral ischemia associated with arterial spasm (117).…”

Microbial Transformation of Nitrogenous Compounds

“…The techniques and different approaches used in microbial transformations have been mentioned and reviewed by several authors [1,4,11,[13][14][15][16][17]. The compounds can be metabolized by using either different pure enzymes or simply cultivated microbial whole cells [18][19][20][21][22].…”

Transformation of Schizandrin into Gomisin A by Use of MicrobialO-Demethylation and Chemical Reactions

“…elegans (ATCC 9245) was selected for this study, because it has been reported that it had a faculty for the O-demethylation of 10, II-dimethoxyaporphine. 10) The fungus was grown with shizandrin in Erlenmeyer's flaks for 15 days. The analysis of the culture broth by high pressure liquid chromatography (HPLC) suggested the existence of four main metabolites (Fig.…”