Synthesis of the bracken ultimate carcinogen and its reactivity toward DNA

Abstract

Synthetic studies on the bracken ultimate carcinogen (3) and its artificial analogues (32, 33) are described. The synthesis of (-) -ptaquilosin (2) the aglycon of a potent carcinogen ptaquiloside (1) from bracken and its (+) - enantiomer (ent- 2) was achieved starting with (+) -dimenthyl (1 R, 2 R) -cyclopentane-1, 2-dicarboxylate. Dehydration of ptaquilosin (2) under weakly basic conditions led to the ultimate carcinogen (3). DNA cleaving activities of both enantiomers (3) were compared, the one (3) derived from natural (-) -ptaquilosin (2) being more efficient. Reactivities of the ultimate carcinogen (3) toward DNA are described. DNA was shown to be alkylated at the particular sites of purine bases and to undergo cleavage. The molecular mechanism of DNA cleavage with the ultimate carcinogen (3) was disclosed using deoxytetranucleotide d (GTAC) as a model DNA substrate. © 1995, The Society of Synthetic Organic Chemistry, Japan. All rights reserved.