Carcinogenic Derivatives of Cyclopenta [a]phenanthrene

Abstract

ALTHOUGH much is known concerning the relationship between carcinogenic activity and structure in hydrocarbons containing four or more condensed aromatic rings, comparatively little work has been reported on derivatives of 16,17-dihydro-15H-cyclopenta[a]phenan-threne (8) which have the same carbon ring structure as the natural steroid hormones. Butenandt and Dannenberg¹ have shown that of the methyl derivatives of this hydrocarbon, which is itself inactive, only the 7- and 11-mono-methyl and 11,12-dimethyl compounds showed any carcinogenic activity, and even then the activity was very weak in skin painting experiments and non-existent by subcutaneous injection. It is noteworthy that 1,2,3,4-tetramethylphenanthrene exhibited activity of this order^2,3. Later, in an investigation of the nature of the carcinogenic products formed from cholesterol during dehydrogenation with chloranil, Dannenberg² found that the D-ring unsaturated compounds (9) and (6) both possessed weak activity. Since these compounds were oxidized, by osmium tetroxide, at the D-ring double bond rather than at the “phenanthrene” double bond, the former was designated the K-region in these hydrocarbons.