A Highly Abbreviated Synthesis of Dibenzo[def,p]chrysene and Its 12-Methoxy Derivative, a Key Precursor for the Synthesis of the Proximate and Ultimate Carcinogens of Dibenzo[def,p]chrysene.
Dibenzo[def,p]chrysene (DBC) (1), is by far the most mutagenic and toxic polycyclic aromatic hydrocarbon identified. Its metabolic activation leads to trans-11,12-dihydroxy-11,12-dihydro-DBC (2), which is further metabolized to the ultimate metabolite, anti-trans-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydro-DBC (3), that binds to DNA causing mutations and ultimately tumor induction. We report a facile route for the syntheses of DBC (1) and its 12-methoxy derivative (12-methoxy-DBC) (13), a key intermediate for the synthesis of 2 and 3, using a Suzuki cross-coupling approach.
Sharma
Arun K
AK
Institute for Cancer Prevention, American Health Foundation Cancer Center, 1 Dana Road, Valhalla, New York 10595, USA. asharma@ifcp.us
Kumar
Subodh
S
Amin
Shantu
S
D001580:Benzopyrenes / Q000138:chemical synthesis* / Q000633:toxicity; D002273:Carcinogens / Q000138:chemical synthesis* / Q000633:toxicity; D015394:Molecular Structure
D001580:Benzopyrenes; D002273:Carcinogens; C041517:dibenzo(a,l)pyrene