Nucleotides and Nucleosides

Analyses of nucleosides have included studies of a series of uridine derivatives. Thus 5-chlorouridine (23) has been shown to be isomorphous with 5-bromouridine. In both molecules the sugar conformation is C(20-endb, the torsion angle (x) for the glycosidic bond is —51.4°, whidi places the 

The synthesis of 2 -0-tetrahydropyranyladenosine (28) as an intermediate in oligoribonucleotide synthesis led to a mixture of two diastereoiso-mers, differing at C(20, but readily separable and with different properties e.g. [a] -8°, m.p. 171—172.5 °C [ ] -130°, m.p. 199—200 C). Similar results had previously been obseved for the 2 -0-tetrahydropyranyl ethers of uridine and AT(4)-benzoylcytidine. An analysis of the more laevorotatory isomer of (28) proves that it has the absolute stereochemistry (2T-S), and by analogy defines the absolute stereochemistries of the uridine and cytidine derivatives also as (2 -S). 

The nucleotide deoxycytidine 5 -phosphate monohydrate (29) is found to exist as a zwitterion with a protonated nitrogen. The conformation of the molecule is described as C(3 )-exo C(2 )-endo, x — ( ri), and the 

C(4 )-C(5 ) conformation is gauche-gauche. The value of the gjycosyl torsion angle (—6°) is of novel interest, since this is the first recorded instance of a small negative angle. Whereas this nucleotide, and all of the nucleosides which have been discussed, display anti conformations for the glycosidic 

Related structures which have been examined include 6-chloro-9-(3,+di-0-acetyl-2-deoxy-/J-D-ribopyranosyl)purine (31), of interest because the a-anomer exhibits anti-tumour activity whereas the /3-anomer does not. 

Sundaralingam, in Synthetic Procedures in Nucleic Acid Chemistry, W. W. Zorbach and R. S. Tipson, eds., John Wiley and Sons, Inc., New York, 

Compound Description Displacement from plane (A) References 

D-Ribofuranosyl-6-purine- thiol C-2 endo 0.612,0.632 (two independent molecules) 84 

Guanosine 5 -phosphate Barium inosine 5 -phos- C-3 endo C-2 endo 0.515 89 

Disodium inosine 5 -phosphate C-2 endo (two independent molecules) 90 

Purine nucleosides are formed when a dilute solution of a purine, together with ribose or deoxyribose and MgClj is evaporated to dryness and heated at 100° C (Fuller et al., 1972). Yields of several percent of the a- and j3-isomers of adenosine, guanosine and xeinthosine, and about 10% of a- and j3-inosine are obtained. Interestingly, a mixture of the salts present in sea water produces even higher yields (15% of inosines). The simplicity of this reaction makes it attractive as a potential source of nucleosides. Unfortunately, it has not been possible to synthesize the pyrimidine nucleosides in this manner and there is as yet no satisfactory synthesis of these compounds. 

P212i21 Z = 4 Dx = 1.521 R = 0.033 for 1,136 intensities. The crystal structure is isomorphous with that of formycin monohydrate.133 The glycosyl disposition is high anti (103.7°) and the D-ribosyl group has the 2T, pucker (144.5°, 41.9°). The orientation about the exocyclic, C-4 -C-5 bond is trans (179.1°). Errors the O-l x-coordinate should be 0.3307, instead of0.3007. The atom following 0-4 should be C-5, not 0-5.  

C2 Z = 4 Dx = 1.491 R = 0.033 for 1,002 intensities. The glycosyl disposition is anti (-28.4°) and bears an enantiomeric relationship to the usual anti range for /3-nucleosides. The D-ribosyl group has the 3T2 

P2J2A Z = 8 Dx = 1.931 R = 0.034 for 2,321 intensities. There are two molecules in the asymmetry unit, and both exhibit the syn disposition (—84.5°, + 76.1°) for the base. The conformation of the D-ribosyl group is 3T4 (28.5°, 39.4°) in molecule A and 3T2 (359.9°, 36.2°) in molecule B. The exocyclic, C-4 -C-5 bond torsion-angle is gauche+ for both molecules (55.2°, 59.7°). The purine bases of the crystallograph-ically independent molecules are paired by N-l-H 0-6 hydrogen bonds across a pseudo-two-fold axis. The bases are stacked such that the Br atoms are tucked under the pyrimidine moiety of the adjacent 

C10HuNO5 2,2 -Anhydro-(l-/3-D-arabinofuranosyl-2-hydroxy-4-pyri-done)136 

C222j Z = 8, Dx = 1.443 R = 0.04 for 1,330 intensities. The crystal structure is isomorphous with that of 2-thioguanosine monohydrate.141 The glycosyl disposition is anti (58.6°), and the 2-deoxy-D-erythro-pentofuranosyl group has the 2T1 pucker (149.4°, 38.8°). The orientation about the exocyclic, C-4 —C-5 bond is trans (—174.4°). The bases are paired, through the N-l-H N-7 and N-2-H S hydrogen- 

Trinucleotides, because they are high-energy compounds, are important participants in various metabolic processes. It has already been mentioned that ATP is the principal chemical energy source in the organism and is required for such physiologic processes as muscle contraction and maintenance of electrolyte balances in the organism. UTP is required in the biosynthesis of complex carbo- 

Base Sugar Nucleoside 5 -Mononucleotide 5 -Dinucleotide 5 -Trinucleotide 

Adenine Ribose Adenosine Adenylic acid adenosine monophosphate (AMP) Adenosine diphosphate (ADP) Adenosine triphosphate (ATP) 

Guanine Ribose Guanosine Guanylic acid guanosine monophosphate (GMP) Guanosine diphosphate (dADP) Guanosine triphosphate (GTP) 

Hypoxanthine Ribose Inosine Inosinic acid inosine monophosphate (IMP) Inosine diphosphate (IDP) Inosine triphosphate (ITP) 

The nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are the molecules that play a fundamental role in the storage of genetic information, and the subsequent manipulation of this information. They are polymers whose building blocks are nucleotides, which are themselves combinations 

Before we analyse nucleotide stmcture in detail, it is perhaps best that we consider the nature of the 

Essentials of Organic Chemistry Paul M Dewick 2006 John Wiley Sons, Ltd 

The bases are monocyclic pyrimidines (see Box 11.5) or bicyclic purines (see Section 11.9.1), and all are aromatic. The two purine bases are adenine (A) and guanine (G), and the three pyrimidines are cytosine (C), thymine (T) and uracil (U). Uracil is found only in RNA, and thymine is found only in DNA. The other three bases are common to both DNA and RNA. The heterocyclic bases are capable of existing in more than one tautomeric form (see Sections 11.6.2 and 11.9.1). The forms shown here are found to predominate in nucleic acids. Thus, the oxygen substituents are in keto form, and the nitrogen substituents exist as amino groups. 

The phosphate group of nucleotides is attached via a phosphate ester linkage, and may be attached to 

Owing to the great biological importance of this class of compounds, the 13C NMR spectra of a considerable number of nucleosides and nucleotides and their aglycones have been reported in the literature [147,428, 460, 676, 735, 748-760]. As demonstrated by the spectra of flavin adenine dinucleotide (Fig. 5.9), the 13C NMR spectra of nucleosides and nucleotides have two groups of signals  

Kirk-Othmer Encyclopedia of Chemical Technology (4th Edition) 

The naturally occurring C-nucleosides containing C-glycosyl linkages are shown in Table 1. 

Showdomycin. Showdomycin (2-p-D-ribofuranosyhnaleimide) (7) is a maleimide C-nucleoside antibiotic synthesi2ed by S. showdoensis-, isoshowdomycin (8) and maleimycin (9) have also been isolated (1—6). Showdomycin is not phosphorylated by nucleoside kinase and is not a substrate for nucleoside phosphorylase. Once (7) enters the cell, it blocks the uptake of glucose and other nutrients. 

Most recendy the stmcture of pyrrolosine has been shown to be an isomeric C-nucleoside analogue of 9-dea2ainosine, which is 7-(P-D-ribofuranosyl)-4-oxo-3Ff,5E -pyrrolo[3-2-i/ pyrimidine (29). Pyrrolosine inhibits development of starfish embryos. 

Purine A Nucleosides. The purine A/-nucleoside antibiotics are given in Tables 2 and 3. 

C9H9N309-H20 5-Nitro-l-(/ -D-ribosyluronic acid)uracil, monohydrate (NRURAM11)140 

C9H12K2N2012P2 3 H20 Uridine 5 -(dipotassium diphosphate), trihydrate (KURDPI)150 

C9H13N209P,H20 Uridine 3 -monophosphate, monohydrate (URID-MP10)152 

P212121 Z = 4 DX = 1.56 R = 0.028 for 1,206 intensities. The cytosine base is protonated at N-3, and has the anti (45.6°) disposition. The D-ri-bosyl group is 2E (162.3°, 40.6°). The exocyclic, C-4 -C-5 bond torsion-angle is gauche+ (53.1°). The Cl- ion is hydrogen-bonded to the base sites N-3, N-4, and the 2-hydroxyl oxygen atom of different molecules. 

C9H15N408P H20 5-Amino-l-/ -D-ribofuranosylimidazole-4-carboxam-ide 5 -phosphate, monohydrate (ARFIMP10)186 

P24 Z =2 Dx = 1.494 R = 0.038 for 1,228 intensities. This structure is isomorphous with that of 5-bromo-2 -deoxyuridine.41 The confor- 

P21 Z = 2, Dx = 1.57, R = 0.046 for 1,444 intensities. The conformation of the D-arabinosyl group is 3T2, the glycosyl disposition is anti (36°), and the exocyclic C-4 -C-5 bond torsion-angle is —56°. The sulfur atom is hydrogen-bonded to the hydroxyl groups 0-2 -H and O-3-H of different molecules. 

C10HnN5O3 H20 Formycin monohydrate46 7-amino-3-/3-D-ribo-furanosylpyrazolo [4,3-d ] py rim idine monohydrate 

Pyrazomycin. Pyrazomycin (11), 3-(l-p-D-ribofuranosyl)-4-hydroxypyrazole 5-carboxamide, is isolated from S. Candidas (1—4,9,10). The incorporation of [2-13C]acetate and [1- and U-14C]glutamate into the four contiguous carbons of pyrazomycin has been reported (11,12). Pyrazomycin 5 -phosphate inhibits orotidylic acid decarboxylase. Pyrazomycin inhibits adenosine phosphorylation and decreases the incorporation of deoxyuridine into DNA of Novikoff hepatoma cells in culture. It also inhibits the growth of tumor cells and the cytopathic effects of vaccinia, herpes simplex, vesicular stomatitis, Newcasde disease, measles, Sindbis, polio, hepatitis A, and coxsackie viruses (13,14). The inhibitory action of (11) on viral multiplication is reversed by uridine. 

P2i2i2i Z = 8 D, = 1.84 R = 0.059 for 2,587 intensities. In the asymmetrical unit, there are two molecules that have similar conformations. The glycosyl dispositions are anti (45.8°, 40.9°) in both molecules. The D-ribosyl conformation is (157.6°, 32.1°) in one molecule, and (165.1°, 31.9°) in the other. The exocyclic, C-4 -C-5 bond torsion-angles dire gauche (51.9°, 53.9°) in both molecules, and the C-5 -0-5 bond torsion-angles are trans (172.5°, 176.6°). The two UDP molecules form a dimer coordinated by three ions. There is no metal-ion or water bridge between the pyrophosphate chain and the uracil base of the same molecule. The three ions are coordinated by oxygen atoms of 

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Michelson, A M. 1963, The Chemistry of Nucleosides and Nucleotides, Academic Press New York London... 

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