Uracils acid-catalyzed

In the course of their studies of pseudouridine,164 Asbun and S. B. Binkley183 reported the synthesis of 5-/3-D-arabinofuranosyl- and 5-/3-D-xylofuranosyl-uracil (258 and 259) by the acid-catalyzed ring-closure of the corresponding alditol derivatives. The configuration at the anomeric carbon atom was determined on the basis of optical rotatory dispersion studies. 

The products (50)—(53) can be converted into their tri-O-acetates by acid-catalyzed acetylation, whereas hydrogenation gives the corresponding aminohexosyl-uracils (54)—(57) i h... 

An amino or hydroxy group facilitates 5-bromination even in aqueous solution. A -bromosuccinimide (NBS) and molecular bromine are the commonest reagents used. In uracils, cytosines, and barbituric acids, products of both addition and substitution can be identified in aqueous solution, and 5,5-dibromo products are common. In the bromination of uracils, addition products, including covalent hydrates, form rapidly, and the acid-catalyzed dehydration step to 5-bromouracils is much slower. Cytosine and related compounds behave similarly <1994HC(52)1, 1996CHEC-II(6)93>. 

Botta and coworkers recently developed an Oxone cleavage methodology for the solid-phase synthesis of substituted uracils (equation 57)165. Whereas some common methods of thioether cleavage, such as reduction with Na/NH3, acid catalyzed hydrolysis, heavy metal ions followed by treatment with hydrogen sulfide and iodotrimethylsilane proved to be unsuccessful for this reduction, Oxone was shown to be an efficient and selective reagent for cleavage of polymer bound thiouracils. 

In enzymes, folic acid catalyzes the iV-formylation of amines and the 5-hy-droxymethylation of uracil. None of these reactions has been performed in enzyme-free systems. 

Walczak and co-workers employed an acid-catalyzed Dimroth rearrangement in their novel transformation of 5-cyanouracil derivatives. Treatment of 5-cyano uracil 150 with l-amino-2-hydroxypropanone in anhydrous ethanol at room temperature gave the corresponding Dimroth product 151 in 51% yield. 

Cyclic orthoformates are stable in alkaline media, but undergo acid-catalyzed hydrolysis under very mild conditions. Thus the half-time of hydrolysis of 2, 3 -0-methoxy-methyleneuridine (93a B = uracil) was found [166b] to be ca. 10 min in O.OliV-hydrochloric acid at 20°. The immediate hydrolysis product was a mixture of 2 - and 3 -0-formyluridines which could be deformylated readily at or above pH 7 [166b]. The use of the methoxy- and ethoxy-methylene protecting groups has so far been restricted mainly to oligoribonucleotide synthesis [52, 169, 170]. 

The aerobic degradation of several azaarenes involves reduction of the rings at some stage, and are discussed in Chapter 10, Part 1. Illustrative examples include the degradation of pyridines (3-alkyl-pyridine, pyridoxal) and pyrimidines (catalyzed by dihydropyrimidine dehydrogenases). Reductions are involved in both the aerobic and the anaerobic degradation of uracil and orotic acid. 

Pd(0)-catalyzed substitution reaction, a novel, mild reduction of a-nitro ester to an amino acid ester with TiCl3, and an improved procedure for uracil ring formation. 

The catalytic efficiency of this enzyme to hydrolyze 5-fluoro-5,6-dihydro-uracil was found to be approximately twice that toward 5,6-dihydrouracil [152], 2-Fluoro-/3-alanine can either be eliminated via the bile after conjugation with bile acids, or be converted to fluoroacetate (4.238) [153], The latter metabolite is transformed to fluorocitrate, a potent inhibitor of the aconi-tase-catalyzed conversion of citrate to isocitrate. This inhibition probably explains the clinical neurotoxicity of 5-fluorouracil [154] [155],... 

An interesting transformation of carbamoylaspartic acid (30a) or ethoxy-carbonylasparagine (30b) to uracil (31) was performed by electrochemical oxidative decarboxylation.77 The same ring-closure reaction occurs in a biological system via an enzyme-catalyzed oxidation. Good yields and mild conditions of the electrochemical transformations give promise of wide application [Eq. (34)]. 

A close look at this reaction reveals that in the opposite direction, the reaction is of the phosphorolysis type. For this reason, the enzymes catalyzing the reaction with ribose-l-phosphate are called phosphorylases, and they also participate in nucleic acid degradation pathways. Purine nucleoside phosphorylases thus convert hypoxanthine and guanine to either inosine and guanosine if ribose-l-phosphate is the substrate or to deoxyinosine and deoxyguanosine if deoxyribose-1-phosphate is the substrate. Uridine phosphorylase converts uracil to uridine in the presence of ribose-l-phosphate, and thymidine is formed from thymine and deoxyribose-l-phosphate through the action of thymidine phosphorylase. 

Aldehyde Oxidase. This enzyme is usually found in similar locations to xanthine oxidase or dehydrogenase and has been isolated from insects, birds, and mammals (20, 21). Aldehyde oxidase seems to be a poor choice of name for this enzyme because, while it oxidizes aldehydes to carboxylic acids, it also accepts a variety of purines and pyrimidines as oxidizable substrates. For example, aldehyde oxidase catalyzes the conversion of 2-hydroxypyrimidine to uracil and of adenine to 8-hydroxy-adenine (25). It appears that xanthine oxidase and aldehyde oxidase are... 

Kornberg s work on the biosynthesis of deoxyribonucleic acid has shown that enzymes in Escherichia coli extracts catalyze the formation of the 5-triphosphates of 2-deoxyadenosine, 2-deoxyguanosine, 2-deoxycyti-dine, and thymidine from the corresponding monophosphates in the presence of adenosine 5-triphosphate, but fail to catalyze phosphorylation of deoxyuridine 5-phosphate this finding could explain why uracil is not a constituent of deoxyribonucleic acid. 

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