49 わらびの究極発癌物質および人工類縁物質による核酸の化学修飾(口頭発表の部)

概要

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Ptaquiloside (1) is a potent carcinogenic compound isolated from the bracken fern Pteridium aquilinum var. latiusculum. Dienone 2 generated from ptaquiloside (1) acts as an alkylating agent toward nucleophiles and is regarded as the ultimate carcinogen. We have investigated chemical modification of DNAs by dienone 2 and the synthetic analogues, 3 and 4. Starting from ethyl 3,3-dimethylacrylate and anhydride 6, dienone 3 was synthesized by the sequence: 5+6→7→8→9→10→11→12→13→3; dienol 4 was prepared by the reaction of 3 with methyllithium. Synthetic dienone 3 and dienol 4 have been found to possess the DNA cleaving activity comparable to that of natural dienone 2. Modification of salmon sperm DNA by natural and synthetic dienones, 2 and 3, was made: on thermal hydrolysis of the modified DNA the purines alkylated at specific sites were isolated and characterized (14 and 15 from 2. 16 and 17 from 3). Cleavage of double-stranded DNA by dienone 2 was examined using ^<32>P end-labeled DNA fragments: the adenine-specific cleavage of DNA fragments occurred under neutral conditions (37℃), while on piperidine treatment (90℃) of DNA fragments that reacted with dienone 2 the purine-specific cleavage of DNA fragments was observed. Reaction of tetranucleotide d(GTAC) with dienone 2 afforded two kinds of alkylated tetranucleotides and their structures were elucidated.
天然有機化合物討論会の論文
1992-09-10