Synthesis of 5-Substituted Pyrimidines via Formaldehyde Addition<sup>1</sup>

Cline, Richard E.; Fink, Robert M.; Fink, Kay

doi:10.1021/ja01519a056

Cited by 223 publications

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“…Formaldehyde is generated "in situ" by the radical degradation of FA (72)(73)(74)(75). Once formed, it can add on the C-5 electrophilic position of uracil to give 5-hydroxymethyl uracil as intermediate, which then rearranges to thymine (76). Sugars.…”

Section: Resultsmentioning

confidence: 99%

Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation

Saladino

Carota

Botta

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

165

157

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Liquid formamide has been irradiated by high-energy proton beams in the presence of powdered meteorites, and the products of the catalyzed resulting syntheses were analyzed by mass spectrometry. Relative to the controls (no radiation, or no formamide, or no catalyst), an extremely rich, variegate, and prebiotically relevant panel of compounds was observed. The meteorites tested were representative of the four major classes: iron, stony iron, chondrites, and achondrites. The products obtained were amino acids, carboxylic acids, nucleobases, sugars, and, most notably, four nucleosides: cytidine, uridine, adenosine, and thymidine. In accordance with theoretical studies, the detection of HCN oligomers suggests the occurrence of mechanisms based on the generation of radical cyanide species (CN·) for the synthesis of nucleobases. Given that many of the compounds obtained are key components of extant organisms, these observations contribute to outline plausible exogenous high-energy-based prebiotic scenarios and their possible boundary conditions, as discussed.origin of life | formamide | prebiotic syntheses | nucleosides | meteorites H ypothesizing formamide (FA) as parent molecule, we explored its potentiality in synthetic processes when exposed to proton irradiation. The purpose of this analysis is to verify a possible prebiotic scenario consisting of FA, considered here as starting one-carbon atom material, of proton beams mimicking solar energetic particles as energy source, and of meteorites as catalysts. The rationale of this approach is that the results could help in outlining exogenous prebiotic models and their boundaries.FA (NH 2 CHO) is becoming one of the most intensively studied precursors for prebiotic syntheses of compounds potentially relevant for the origin of life (1-4). FA is a ubiquitous molecule in the universe. It has been detected in galactic centers (Sgr A and Sgr B), in star-forming regions of dense molecular clouds, in high-mass young stellar objects, in the interstellar medium and in comets and satellites (5)(6)(7)(8)(9)(10)(11)(12)(13)(14).With the appropriate mineral as catalyst, different ensembles of intermediates of genetic and metabolic apparatuses are simultaneously synthesized from FA under thermal conditions (i.e., by heating liquid FA between 333 and 453 K at room pressure). DNA and RNA components (15-21), amino acids (22, 23), sugars (24), and carboxylic acids (25, 26) have been obtained. Minerals tune the selectivity of these transformations (1, 2), the mechanistic pathways for the synthesis of nucleobases requiring pyrimidine (27-30) or imidazole intermediates (31,32).Within the solar system, ionizing cosmic radiation is generated by the Sun [solar cosmic rays (SCRs), primarily protons accelerated by flares and coronal mass ejections to energies typically of tens to hundreds megaelectronvolts] and is also formed by particles coming from the deep universe [galactic cosmic rays (GCRs)] (33). The SCRs and GCRs differ in their components and energy spectra, but their overwhelming co...

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Section: Resultsmentioning

confidence: 99%

Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation

Saladino

Carota

Botta

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

165

157

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“…3A, inset) and is similar to that of 5-methyluridine (mW ; Littlefield and Dunn, 1958) rather than that of mnm5 s' U (Shaw et al, 1958). By using the molar absorption coefficient of m5U (Cline et al, 1959), the amount of nucleoside N* was estimated to be much the same as those of m' U and 2-thiocytidine (s'C) each of which occupies a single position in argU tRNA. This indicates that uridine in position 34 is fully modified to nucleoside N*.…”

Section: Modified Nucleotide (Pn*) In Position 34 Of Argu Trnamentioning

confidence: 86%

A modified uridine in the first position of the anticodon of a minor species of arginine tRNA, the argU gene product, from Escherichia coli

Sakamoto

Kawai

Niimi

et al. 1993

European Journal of Biochemistry

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The argU (dnaY) gene product, a minor tRNAArg, from Escherichia coii has the anticodon N*CU with an unidentified modified nucleoside N* in position 34 [Kiesewetter, S., Fisher, W. & Sprinzl, M. (1987) Nucleic Acids Res. 15, 3184]. In the present study, argU tRNA was purified from E. coli A 19 strain and nucleoside N* was characterized by the TLC and HPLC analyses. Nucleoside N* was found to be different from any naturally occurring modified nucleosides. From unfractionated E. coli tRNA species, nucleoside N* was prepared in an amount sufficient for 1H‐NMR experiments. By the analyses of one‐dimensional and two‐dimensional NMR spectra, nucleoside N* was suggested to be 5‐methylaminomethyluridine (mnm5U), which was confirmed by comparison with a chemically synthesized preparation of mnm5U. Thus, the occurrence of mnm5U in mature tRNA was found for the first time. Further, the modification of U(34) to mnm5U in this tRNA was found to contribute to the strict recognition of two degenerate codons terminating in A and G.

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“…(R,0.44,CHC1,8:2). Mother liquors showed a single quenching spot (R, 0.5) but the nucleoside did not crystallize.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Properties of 5-Hydroxymethyl-2′-deoxyuridine and its α-Anomer

Gupta¹,

Bubbar²

1971

Can. J. Chem.

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The synthesis and properties of 5-hydroxymethyldeoxyuridine (6) and its a-anomer 7 are described. Treatment of 5-hydroxymethyluracil(2) with trimethylchlorosilane in the presence of triethylamine gave 2,4,5-tris(trimethylsily1)-5-oxymethyluracil (3) in excellent yield (92%) which, upon condensation with 3,5-di-(0-p-toluoyl)-2-deoxy-D-ribofuranoy chloride in acetonitrile at room temperature, furnished an anomeric mixture of substituted nucleosides p-anomer (4) and a-anomer (5) in high yield 90% (by a fusion method (12) yield of blocked nucleosides was 70%). Compound 4 was the major product formed by both methods and was recovered as a crystalline solid in high yield. However, condensation of 3 with chlorosugar in benezene with mercuric chloride as a catalyst at room temperature gave a mixture of protected nucleosides; the amount of 5 formed was appreciably higher (34%) and was isolated as a microcrystalline solid from mother liquors in low yield (without the catalyst nucleosides were formed in low yield 30%). Removal of the blocking groups by alcoholysis gave 6 and 7 in high yields. The structure was confirmed by n.m.r. studies, U.V. and i.r. absorption spectra, elemental analysis, and by conversion of 4 to p-thymidine (8).Canadian Journal of Chemistry, 49, 719 (1971) 5-Hydroxymethyl-2'-deoxyuridylate replaces thymidylate of the DNA of a virulent group of Bacillus subtilis bacteriophages (1-4). Its biosynthesis from deoxyuridylate and 5,10-methylene tetrahydrofolate is catalyzed by the enzyme, hydroxymethylase (5, 6), which is analogous to the hydroxymethylation of deoxycytidylate of Escherichia coli T-even bacteriophages (7). The enzymic transformation of thymidine to 5-hydroxymethyldeoxyuridine (6), has been demonstrated in Neurospora, and 5-substituted pyrimidines may be intermediates in the transformation of thymine to RNA pyrimidines (8).The synthesis of 6 from deoxyuridine under acidic conditions3 was reported by Cline et al. (9), and the base-catalyzed hydroxymethylation4 of deoxyuridine has been described by Baker et al. (10). Recently the chemical synthesis of 6 using a mercury procedure5 has been reported (I 1); in this method the removal of the benzyl group by 'This work was supported by the Medical Research Council of Canada (Grant MA-3136).2To whom correspondence should be sent. 3From a mixture of products, 6 was isolated by ion exchange chromatography in poor yield (19%). Using the described conditions, Baker et al. (10) reported an even lower yield (< 10%).4Although 6 was the main product under basic conditions, it could not be induced to crystallize and was difficult to isolate in the pure state. 5Mercury salt of 5-benzyloxymethyluracil was coupled with 3,5-di-(0-p-toluoy1)-D-ribofuranosylchloride, and from the reaction mixture, the blocked nucleoside 1-(2-deoxy-3,5-di-(O-p-toluoyl)-~-~-ribofuranosyl-5-benzyloxymethyluracil (9) was isolated in a yield of 57%. The removal of the benzyl group by catalytic hydrogenation yielded 4 which, upon deacylation gave 6. catalytic hydrogenation is a critic...

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Synthesis of 5-Substituted Pyrimidines via Formaldehyde Addition¹

Cited by 223 publications

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Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation

Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation

A modified uridine in the first position of the anticodon of a minor species of arginine tRNA, the argU gene product, from Escherichia coli

Synthesis and Properties of 5-Hydroxymethyl-2′-deoxyuridine and its α-Anomer

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Synthesis of 5-Substituted Pyrimidines via Formaldehyde Addition1

Cited by 223 publications

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Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation

Meteorite-catalyzed syntheses of nucleosides and of other prebiotic compounds from formamide under proton irradiation

A modified uridine in the first position of the anticodon of a minor species of arginine tRNA, the argU gene product, from Escherichia coli

Synthesis and Properties of 5-Hydroxymethyl-2′-deoxyuridine and its α-Anomer

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Synthesis of 5-Substituted Pyrimidines via Formaldehyde Addition¹