CCH 2
O
O
CH 3
CH 3 H +H 3 C HA CCH 2 H
CH 3
H 3 C
3
O
OCH
i) Bonding in the protonated epoxide is unsymmetrical, which the more highly
substituted carbon atom bearing a considerable positive charge; the reaction is
SN1 like.
CCH 2
O
O
δ+
CH 3
CH 3 H + H 3 C CCH 2 H
CH 3
H 3 C
H^3
δ+
This carbon resembles a 3o carbocation
H
Protonated epoxide
O
+OCH
The Chemistry of Epoxides, Carcinogens, and Biological Oxidation
- Certain molecules from the environment becomes carcinogenic by “activation”
through metabolic processes that are normally involved in preparing them for
excretion.
- Two of the most carcinogenic compounds known: dibenzo[a,l]pyrene, a
polycyclic aromatic hydrocarbon (PAH) and aflatoxin B 1 , a fungal metabolite.
- During the course of oxidative processing in the liver and intestines, these
molecules undergo epoxidation by enzymes called P450 cytochromes.
i) The epoxides are exceptionally reactive nucleophiles and it is precisely because
of this that they are carcinogenic.
ii) The epoxides undergo very facile nucleophilic substitution reactions with
DNA.
iii) Nucleophilic sites on DNA react to open the epoxide ring, causing alkylation of
the DNA by formation of a covalent bond with the carcinogen.
iv) Modification of the DNA in this way causes onset of the disease state.
