Biodegradation Predictive Worksheet Reasoning: Permethrin

1. What was the first thing you focused on to guide your development of a pathway(s)?
E1 Initial thoughts: One of the rings must be cleaved first. The five membered ring contains bonds susceptible to hydrolytic cleavage. Hydrolytic bond cleavage reactions can generate an intermediate; a disubstituted benzene that is further metabolized by known reactions.
E2 Ether hydrolysis, ester hydrolysis, and reductive dehalogenation (Order is not important here).
E3 Answer to 1 in the check list: may be limiting
Answer to 2 in the check list: yes
Answer to 8 in the check list: partly yes
E4 Ester bond cleavage probably occurs readily

2. How did you proceed after your initial focus point?
E1 Following the hydrolytic cleavages, I predict that a dioxygenation followed by a dehydrogenation or elimination will set up the six-membered ring for cleavage. It is reasonable that this dioxygenation will also remove one of the side groups. Both possible removals are shown.
E2 Cyclopropane ring is not degraded?
E3 answer to 7 in the check list: yes --- oxygenolytic ester cleavage
answer to 8a in the check list: yes (aromatic structures only)

Note: I did not include an ether hydrolase reaction since I do not know of any good examples of this type of reaction in biodegradation.
E4 (1). Biaryl ether bond cleavage(?). Ring oxidation may occur without ether bond cleavage (by analogy to biphenyl).
(2). Ether bond cleavage may be rate limiting.