- Prebiotic Photochemical Coproduction of Purine Ribo- And Deoxyribonucleosides
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The hypothesis that life on Earth may have started with a heterogeneous nucleic acid genetic system including both RNA and DNA has attracted broad interest. The recent finding that two RNA subunits (cytidine, C, and uridine, U) and two DNA subunits (deoxyadenosine, dA, and deoxyinosine, dI) can be coproduced in the same reaction network, compatible with a consistent geological scenario, supports this theory. However, a prebiotically plausible synthesis of the missing units (purine ribonucleosides and pyrimidine deoxyribonucleosides) in a unified reaction network remains elusive. Herein, we disclose a strictly stereoselective and furanosyl-selective synthesis of purine ribonucleosides (adenosine, A, and inosine, I) and purine deoxynucleosides (dA and dI), alongside one another, via a key photochemical reaction of thioanhydroadenosine with sulfite in alkaline solution (pH 8-10). Mechanistic studies suggest an unexpected recombination of sulfite and nucleoside alkyl radicals underpins the formation of the ribo C2′-O bond. The coproduction of A, I, dA, and dI from a common intermediate, and under conditions likely to have prevailed in at least some primordial locales, is suggestive of the potential coexistence of RNA and DNA building blocks at the dawn of life.
- Xu, Jianfeng,Green, Nicholas J.,Russell, David A.,Liu, Ziwei,Sutherland, John D.
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supporting information
p. 14482 - 14486
(2021/09/18)
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- Synthesis and Biological Evaluation of Pyrrolo[2,1-f][1,2,4]triazine C-Nucleosides with a Ribose, 2′-Deoxyribose, and 2′,3′-Dideoxyribose Sugar Moiety
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The synthesis of hitherto unknown pyrrolo[2,1-f][1,2,4]triazine C-nucleosides is described. Structural variations (chlorine, bromine, iodine, and cyano groups) were introduced at position 7 of 4-aza-7,9-dideazaadenine. In addition, pyrrolo[2,1-f][1,2,4]triazine C-nucleosides bearing a 2′-deoxy-, 2′,3′-dideoxy-, and 2′,3′-dehydrodideoxyribose moiety were also prepared. Among these analogues, the pyrrolo[2,1-f][1,2,4]triazine C-ribonucleosides with either a hydrogen atom or cyano group at position 7 of the nucleobase displayed potent cytotoxic activity in a panel of various cancer cell lines.
- Li, Qingfeng,Lescrinier, Eveline,Groaz, Elisabetta,Persoons, Leentje,Daelemans, Dirk,Herdewijn, Piet,De Jonghe, Steven
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- Pyrazolo[1,5- a ]-1,3,5-triazine C-nucleoside as deoxyadenosine analogue: Synthesis, pairing, and resistance to hydrolysis
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The synthesis of a pyrazolo[1,5-a]-1,3,5-triazine C-nucleoside (dA PT), designed to form two hydrogen bonds with a complementary dT residue, is reported. Oligonucleotides including this dA nucleoside analogue possess base-pairing properties similar to those of the parent oligonucleotide. This dA nucleoside analogue is more resistant to acid-catalyzed hydrolysis than dA.
- Lefoix, Myriam,Mathis, Gérald,Kleinmann, Tirtsa,Truffert, Jean-Christophe,Asseline, Ulysse
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p. 3221 - 3227
(2014/05/06)
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- Slow loss of deoxyribose from the N7deoxyguanosine adducts of estradiol-3,4-quinone and hexestrol-3′,4′-quinone.: Implications for mutagenic activity
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A variety of evidence has been obtained that estrogens are weak tumor initiators. A major step in the multi-stage process leading to tumor initiation involves metabolic formation of 4-catechol estrogens from estradiol (E 2) and/or estrone and further oxidation of the catechol estrogens to the corresponding catechol estrogen quinones. The electrophilic catechol quinones react with DNA mostly at the N-3 of adenine (Ade) and N-7 of guanine (Gua) by 1,4-Michael addition to form depurinating adducts. The N3Ade adducts depurinate instantaneously, whereas the N7Gua adducts depurinate with a half-life of several hours. Only the apurinic sites generated in the DNA by the rapidly depurinating N3Ade adducts appear to produce mutations by error-prone repair. Analogously to the catechol estrogen-3,4-quinones, the synthetic nonsteroidal estrogen hexestrol-3′,4′-quinone (HES-3′, 4′-Q) reacts with DNA at the N-3 of Ade and N-7 of Gua to form depurinating adducts. We report here an additional similarity between the natural estrogen E2 and the synthetic estrogen HES, namely, the slow loss of deoxyribose from the N7deoxyguanosine (N7dG) adducts formed by reaction of E2-3,4-Q or HES-3′,4′-Q with dG. The half-life of the loss of deoxyribose from the N7dG adducts to form the corresponding 4-OHE 2-1-N7Gua and 3′-OH-HES-6′-N7Gua is 6 or 8 h, respectively. The slow cleavage of this glycosyl bond in DNA seems to limit the ability of these adducts to induce mutations.
- Saeed, Muhammad,Zahid, Muhammad,Gunselman, Sandra J.,Rogan, Eleanor,Cavalieri, Ercole
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- Facile preparation of protected furanoid glycals from thymidine
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The synthesis of O-silyl- and O-acyl-protected furanose glycals from free thymidine was investigated. The method of glycal formation reported by Pedersen et al. was successfully expanded to include 5-ester (toluoyl) protected glycals as well as various combinations of 5'-ester and 3- and 5- tert-butyldimethylsilyl and tert-butyldiphenylsilyl protection. Gram quantities of furanoid glycals can be prepared in a few days in two-four steps in overall yields ranging from 17 to 80%.
- Cameron, Melissa A.,Cush, Sarah B.,Hammer, Robert P.
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p. 9065 - 9069
(2007/10/03)
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