Uracil nucleosides structures

K.A. Watanabe, T-L. Su, R.S. Klein, C.K. Chu, A. Matsuda, M.W. Chun, C. Lopez, and J.J. Fox, Nucleosides. 123. Synthesis of antiviral nucleosides 5-substituted l-(2-deoxy-2-halogeno-/3-D-arabinofuranosyl)cytosines and -uracils. Some structure-activity relationships. J. Med. Chem. 28 152 (1983). 

Nucleosides. 123. Synthesis of antiviral nucleosides 5-substituted l-(2-deoxy-2-halogeno-p-arabino-furanosyl)cytosines and -uracils. Some structure-activity relationships. J. Med. Chem. 26 152 (1983). 

Attached by a covalent bond to carbon atom 1 of the deoxyribose ring is an amine (and therefore a base), which may be adenine, A (22) guanine, G (23) cytosine, C (24) or thymine, T (25). In RNA, uracil, U (26), replaces thymine. The base bonds to carbon atom 1 of deoxyribose through the nitrogen of the —NH— group (printed in red) and the compound so formed is called a nucleoside. All nucleosides have a similar structure, which we can summarize as the shape shown in (27) the lens-shaped object represents the attached amine. 

Nitrogenous base plus sugar moiety are called nucleosides. Ribonucleic acids (RNA) resemble DNA in that nucleoside monophosphates are joined through phosphodiester bonds. RNAs differ in that the sugars are p-D-ribose units and the pyrimidine uracil is found in place of thymine. Molecular structures and nomenclature for nitrogenous bases, nucleosides, and nucleotides are delineated in Table 2.2. 

In RNA, the base T found in DNA is replaced by uracil, which is similar in structure to T, but lacks the methyl group. The nucleotides in nucleic acids are linked by phosphodiester bonds between the 3 -hydroxyl of one nucleoside and the 5 -hydroxyl of the sugar of its neighbour in the sequence, as was first shown by Alexander Todd3 in 1952 (Figure 4.13). 

Cytosine, thymine, and uracil are pyrimidines along with adenine and guanine they account for the five nucleic acid bases. Pyrimidines are heterocyclic single-ringed compounds based on the structure of pyrimidine. Cytosine, thymine, and uracil, like adenine and guanine, form nucleosides and nucleotides in RNA and DNA. When the bases combine with ribose, a ribo-nucleoside forms and when it attaches to deoxyribose, a deoxyribosenucleoside is formed. Names of the nucleoside are summarized in Table 29.1. These in turn combine with phospho-ryl groups, in a process called phosphorylation, to form their respective nucleotides that form nucleic acids. The nucleotides can be tri, di, and mono phosphate nucleotides similar to the way in which adenine forms ATP, ADP, and AMP. 

Both DNA and RNA contain two major purine bases, adenine (A) and guanine (G), and two major pyrimidines. In both DNA and RNA one of the pyrimidines is cytosine (C), but the second major pyrimidine is not the same in both it is thymine (T) in DNA and uracil (U) in RNA Only rarely does thymine occur in RNA or uracil in DNA The structures of the five major bases are shown in Figure 8-2, and the nomenclature of their corresponding nucleotides and nucleosides is summarized in Table 8-1. 

As in the case of cytosine, several NMR and NQR studies were performed in search of the predominating tautomeric structures of uracil and thymine and their nucleotides and nucleosides. Investigation of PMR spectra of these compounds in nonaqueous solvents, such as dimethyl sulfoxide, localized the mobile protons in a number of 5- and 6-substituted uracils.59,61,328 These and similar studies63,85,329,330 indicated that dilactam structure 32 predominates in uracil compounds in aqueous and nonaqueous solutions as well as in the solid state. Proton and N-15 magnetic resonance spectra of several pyrimidines85 confirmed the diketo structure usually ascribed to uracil. 

Overall NMR and NQR spectroscopy data thus indicate that the diketo structure predominates for uracil, thymine, and their nucleosides or nucleotides. These studies have failed to detect other tautomeric forms of these compounds. 

RNA Nucleosides The four RNA bases are adenine, uracil, guanine, and cytosine. RNA does not use thymine. The structures of these compounds are shown in Figure 12.67. 

A highly interesting and often overlooked aspect of this structure proof was brought out by the titrimetric measurements on nucleosides and their free bases by Levene, Bass, and Simms.1M They reasoned, quite justifiably, that uracil should possess two acidic dissociation constants, because of the presence of two potentially dissociable protons in the molecule. (At that time, the problem as to the position of attachment of the carbohydrate to the nitrogenous base had essentially been diminished to a choice between positions 1 and 6.) They demonstrated in an early paper109(a) that uracil possesses two acidic dissociation constants (9.28 and 18.66). If the sugar radical were substituted on position 6 of uridine, both of the dissociation constants of uracil should be demonstrable in uridine whereas, if substitution by the sugar were on position 1, only one of these pKa values should be observable. 

Figure 1.28 (a) The general structure of a nucleotide, (b) A schematic representation of a section of a nucleic acid chain, (c) The bases commonly found in DNA and RNA. These bases are indicated by the appropriate letter in the structures of Nucleic acids. Thymine is not found in RNA it is replaced by uracil, which is similar in shape and structure, (d) Examples of nucleosides found in DNA and RNA... 

Transfer RNA (Mr s= 25,000) functions as an adapter in polypeptide chain synthesis. It comprises 10-20 percent of the total RNA in a cell, and there is at least one type of tRNA for each type of amino acid. Transfer RNAs are unique in that they contain a relatively high proportion of nucleosides of unusual structure (e.g., pseudouridine, inosine, and 2 -0-methylnucleosides) and many types of modified bases (e.g., methylated or acetylated adenine, cytosine, guanine, and uracil). As examples, the structures of pseudouridine and inosine are shown below. Inosine has an important role in codon-anticodon pairing (Chap. 17). 

Only five common nitrogen heterocycles are used to form these nucleosides. Three compounds have one ring, and are derived from a nitrogen heterocycle called pyrimidine. Two are bicyclic, and are derived from a nitrogen heterocycle called purine. These five amines are referred to as bases. Each base is designated by a one-letter abbreviation, as shown in the names and structures drawn. Note that uracil (U) occurs only in ribonucleosides and thymine (T) occurs only in deoxyribonucleosides. 

Draw the structures of the nucleosides formed from each of the following components (a) ribose + uracil (b) 2-deoxyribose + guanine... 

The C-13 magnetic resonance spectra of the naturally occurring uracils have been interpreted in terms of the diketo structures of the compounds. Similarly the triketo structure 36 has been foundto predominate for l-(jS-D-ribofuranosyl) barbituric acid by a comparison of C-13 spectra of several model nucleosides. Also in the case of 6-hydroxycytidine the equilibrium lies strongly toward the diketo form 37b in comparison with the lactim-lactam form 37a. Very recent N-14... 

Nikkomycins. The nikkomycins (141—159), isolated from S. tendae, are nucleoside-peptide antibiotics (1,4,244,245) as shown in Table 8. Nikkomycins X and Z are structurally identical to neopolyoxins A and C, respectively. Compound (141) is a competitive inhibitor of chitin synthetase. Two new nikkomycins, nikkomycin pseudo-Z and pseudo-J (158, 159), contain a C-glycosidic bond between C-5 of uracil and C-l of... 

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