RESUMO
Oxidative thymine damage was investigated using a new non-heme oxygenation model, Fe(MeCN)6(2+)-H2O2-Ac2O, based on high-spin Fe(MeCN)6(2+) in a non-aqueous solution, Ac2O-MeCN. Thymine and 1,3-dimethylthymine oxidized by the system gave the corresponding trans-thymine glycol derivatives in good yield. Thymineglycol is equivalent to an oxidative product as a measure of oxidative DNA damage in living cells. It is suggested that the activation of Fe(MeCN)6(2+)-H2O2-Ac2O in Ac2O-MeCN forms the oxoiron O=Fe(IV)(AcO)(MeCN)4(+) as an active species via a hetelolytic two-electron mechanism, not a Haber-Weiss-Fenton-type reaction with a one-electron process by treatment with a radical scavenger. In addition, we also demonstrated the transition state (TS) for the interaction between thymine and O=Fe(IV)(AcO)(MeCN)4(+) in the triplet spin (spin multiplicity; M=3). This model of oxidative thymine damage may provide new insight into the oxidative mechanism of thymine glycol production in non-aqueous reactions of thymine.
Assuntos
Compostos de Ferro/química , Timina/análogos & derivados , Timina/química , Dano ao DNA , Modelos Biológicos , OxirreduçãoRESUMO
We investigated the reactions of various 1-naphthols (NPOHs; 1) with p-benzoquinones (Qs), such as 1,4-benzoquinone (BQ) and p-chloranil (CA), as pi-electron acceptors. With electron-rich NPOHs 1a-c, oxidative biaryl coupling and subsequent dehydrogenation reaction took place selectively to give the corresponding 2,2'-binapthyl-1,1'-quinones 3a-c in excellent yield. In the case of electron-deficient NPOHs 1e, f, two different types of reactions occurred in the presence of SnCl4 and ZrO2 under similar conditions: SnCl4 mediated oxidative dimerization and trimerization of NPOH, while ZrO2 promoted electrophilic arylation of Qs with NPOH. The resulting products 3 would be useful synthetic intermediates for naturally occurring diosindigo B, biramentaceone and violet-quinone.
Assuntos
Benzoquinonas/química , Naftóis/química , Compostos Policíclicos/síntese química , Eletroquímica , Transporte de Elétrons , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Oxirredução , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Compostos de Estanho , ZircônioRESUMO
The combination of electrolysis and the Fe(III)(PA)3/O2/CH3CN system was investigated for allylic hydroxylation of octahydronaphthalene derivatives. Substrates with a bridgehead double bond gave the allylic alcohol with alpha-preference, while non-bridgehead olefin did not react smoothly. This system is a useful tool for alpha-selective allylic hydroxylation of octahydronaphthalene derivatives with a bridgehead double bond as model compounds for the AB fused ring of cholesterols.
Assuntos
Naftalenos/química , Ácidos Picolínicos/química , Colesterol/química , Eletroquímica , Hidroxilação , Espectroscopia de Ressonância Magnética , Conformação Molecular , Oxirredução , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier , EstereoisomerismoRESUMO
This paper describes research performed in the Laboratory of Organic Chemistry, Showa Pharmaceutical University. Oxidation reactions involving the oxidase can be divided roughly into two kinds of reactions: The first involves electron removal from an aromatic ring or an active CH-bond. The other reaction involves hydrogen abstraction from an inactive CH-bond. The oxidase models, Fe(DMF)(3)Cl(2)(1+) and Fe(AN)(6)(3+)/AN, which we have synthesized, have been shown to work by the former mechanism, and the models Fe(AN)(6)(3+)-IO(4)(-)/AN, Fe(AN)(6)(2+)-Ac(2)O-H(2)O(2)/AN, Fe(AN)(6)(2+)-2PAH-5Py-Ac(2)O-H(2)O(2)/AN, Fe(PA)(3)(OH(2))-H(2)O(2)/AN and Fe(PA)(3)(OH(2))-O(2)-electrolysis/AN do so by the latter mechanism. Further, we found some iron (II or III)picolinate-H(2)O(2)/AN complexes have the 7 alpha-hydroxylase-like activity.
Assuntos
Ferro/química , Modelos Químicos , Oxirredutases , Acetonitrilas/síntese química , Acetonitrilas/química , Carbono/química , Colesterol 7-alfa-Hidroxilase , Eletrólise , Elétrons , Hidrogênio/química , Ligação de Hidrogênio , Peróxido de Hidrogênio/síntese química , Peróxido de Hidrogênio/química , Oxirredução , Fenol , Ácidos Picolínicos/síntese química , Ácidos Picolínicos/químicaRESUMO
The oxygenation reaction of cholesteryl acetate 1 was examined with the Fe(III)(PA)(3)/O(2)/MeCN system using an electrochemical method. The constant potential technique gave mainly the 7-hydroxylated product stereoselectively, along with the 7-oxo product. This oxygenation system is mechanistically unique, requiring iron catalyst, dioxygen, and both cathode and anode.
Assuntos
Compostos Alílicos/química , Ésteres do Colesterol/química , Ferro/química , Oxigênio/química , Ácidos Picolínicos/química , Compostos Alílicos/metabolismo , Ésteres do Colesterol/metabolismo , Eletroquímica , Hidroxilação , Ferro/metabolismo , Oxigênio/metabolismo , Ácidos Picolínicos/metabolismo , EstereoisomerismoRESUMO
The Stille coupling reaction of the stannylindole 13 with the 5-iodoimidazole derivative 14 (or 27) in the presence of PdCl(2)(PPh(3))(2) gave the corresponding indole-imidazole coupling product 15 (or 28), thereby affording a synthetic approach to 10-methylgranulatimide (7), 15-methylgranulatimide (11), and 10, 15-dimethylgranulatimide (12), as well as 10-methylisogranulatimide B (5).
Assuntos
Alcaloides/síntese química , Alcaloides/isolamento & purificaçãoRESUMO
The Stille coupling reaction of stannylindole 12 with 4-iodoimidazole 13 (or 24) in the presence of PdCl(2)(PPh(3))(2) gave the corresponding indole-imidazole coupling product 14 (or 25), thereby affording a new synthetic approach to the alkaloid granulatimide (7), isolated from the Brazilian ascidian Didemnum granulatum, as well as its structural analogues, 10-methylgranulatimide (23), 17-methylgranulatimide (30), 10,17-dimethylgranulatimide (31).