Diazepam, 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one, is a widely used drug. It is used as an anticonvulsant, sedative, and muscle relaxant, and has a long duration of action (PubChem, 2011).
The fungus Aspergillus niger J/8 N-demethylates diazepam
to form 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2-one. This
demethylation step may be carried out by a transmethylase, hydrolytic
demethylase or one of several different types of oxidative
demethylases, so the generic "A" is used. The diazepin ring in the
demethylated compound is then cleaved. It transiently forms
2-amino-N-(2-benzoyl-4-chlorophenyl)acetamide, which is N-acetylated to
The fungus Penicillium velutinum cleaves the diazepin ring at
the same position without prior N-demethylation and performs the same
N-acetylation, to form
N-(2-benzoyl-4-chlorophenyl-2-acetamido-N-methylacetamide. Other fungi
can demethylate diazepam, but this is the first report of fungal
diazepam ring cleavage (Ambrus et al. 1975).
The following is a text-format diazepam pathway map. An organism which can initiate the pathway is given, but other organisms may also carry out later steps. Follow the links for more information on compounds or reactions. This map is also available in graphic (10k) format.
Aspergillus niger J/8 Penicillium velutinum
| A | diazepam | | cyclohydrolase
| 7-chloro-5-phenyl-3H- | 2-amino-N-(2-benzoyl- | 1,4-benzodiazepin-2-one | 4-chlorophenyl)-N-methylacetamide | cyclohydrolase | N-acetylase | | v v [2-Amino-N-(2-benzoyl-] N-(2-benzoyl-4-chlorophenyl- [4-chlorophenyl)acetamide] 2-acetoamido-N-methylacetamide | | 2-amino-N-(2-benzoyl- | 4-chlorophenyl)acetamide | N-acetylase | v N-(2-benzoyl-4-chlorophenyl)- 2-acetamidoacetamide
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