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Synthese de trichothecadienes-9,12 par une methode faisant intervenir la scission de l'epoxyde-12,13 a l'aide de AQNA dans EtOH, suivie de l'oxydation du sulfure puis de l'elimination de la β-hydroxysulfone intermediaire par 4,5% de Na-Hg/MeOH

Incubation of 3-[3H]fluoranthene with a rat liver microsomal activation system in the presence of calf thymus DNA resulted in radioactivity bound to the DNA. The fluoranthene-modified DNA was enzymatically digested and a DNA adduct elution profile developed using h.p.l.c. The fraction containing the major fluoranthene--DNA adduct was further purified by h.p.l.c. and separated into two subfractions. Treatment of these with perchloric acid liberated guanine in both cases. Evidence that both were N-2 guanine derivatives was based on the pK values of these adducts determined before and after treatment with nitrous acid. The major adduct (70% of total modified deoxyribonucleosides) was further characterized by high resolution, fast atom bombardment mass spectroscopy which yielded a molecular ion consistent with a fluoranthene triol bound to the N-2 position of deoxyguanosine. Synthetic syn and anti 3-[3H]2,3-dihydroxy-1,10b-epoxy-1,2,3-trihydrofluoranthene were reacted directly with DNA and the 8-[3H]-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrofluoranthene was incubated with DNA and microsomes. The DNA from each of these reactions was enzymatically hydrolyzed and h.p.l.c. adduct profiles were developed. The major adduct formed from reaction of the anti 2,3-dihydroxy-1,10b-epoxy-1,2,3-trihydrofluoranthene with DNA and the major N-2 fluoranthene derived adduct had identical elution times on two different h.p.l.c. systems, similar pK values (before and after nitrous acid treatment) and the same u.v. spectra. In addition, derivatization of both adducts with ethyl methanesulfonate yielded identical products, as determined by h.p.l.c. analysis.

The syntheses of diol epoxides of the mutagenic hydrocarbon fluoranthene are described. Standard methodology is applied to the synthesis or targets, but fails for the synthesis of some targets. It has been shown that, two diol epoxides can be assembled by a route utilizing stereoselective, directed epoxidations. Simple molecular orbital calculations have been used to predict the reactivity of the diol epoxides in their opening to triol carbocations. Specific diol epoxides are predicted to be substantially more reactive than their isomers. A more reactive pair of diol epoxides may yield carbocations capable of alkylating cellular genetic material. This prediction is borne out in terms of the relative mutagenicity of the diol epoxides in a bacterial screen. The syntheses and mutation assay of six possible metabolites of fluoranthene (dihydrodiols and diol epoxides) are discussed in this report.

In order to study the single electron transfer between the superoxide ion and an ..cap alpha..,..beta..-unsaturated ketone, cis-2,2,6,6-tetramethylhept-4-en-3-one was chosen as a molecule with appropriate reactivity criteria and without acidic protons. The stereochemistry of recovered starting material and product at low extents of reaction was examined. The reaction process of superoxide rapidly and reversibly transferring to olefin to produce a ketyl radical anion in a cage with O/sub 2/ is proposed.