Pyrimidines glycosidation

See C. E. Ballou, Advances in Carbohydrate Chem., 9, 59 (1954), for a discussion of alkali-sensitive glycosides of enols, including pyrimidine glycosides. 

Gougerotin (= l-[4-Deoxy-4-(sarcosyl-D-seryl) amino-(3-I)-gluco-pyranuramide] cytosine)] (pyrimidine glycoside)... 

Danishefsky and coworkers have used a similar sequence of reactions to synthesize octosyl acid A (144 Scheme 40). Aldehyde (140) readily undergoes a hetero cyclocondensation reaction with diene (8), catalyzed by ZnCb, to give the CF pyrone (141). Reduction of the ketone followed by osmylation, oxidation and introduction of the mesylate gives compound (142). Introduction of the pyrimidine glycoside, followed by an intramolecular displacement of the mesylate through the tin complex (143), gives an intermediate that is converted to octosyl acid A (144) by a series of standard manipulations. 

The most important derivatives of pyrimidines and purines are nucleosides Nucleosides are N glycosides m which a pyrimidine or purine nitrogen is bonded to the anomeric carbon of a carbohydrate The nucleosides listed m Table 28 2 are the mam building blocks of nucleic acids In RNA the carbohydrate component is d ribofuranose m DNA It IS 2 deoxy d ribofuranose... 

Note Flavonoids react with the reagent even at room temperature [1] mycotoxins, steroids, purines, pyrimidines, cardiac glycosides and lipids only react on heating [2, 4-6]. Zirconyl sulfate can be used to replace the zirconyl chloride in the reagent this is reported to result in an increase in the sensitivity to certain groups of substances (e.g. cholesteryl esters, triglycerides) [4]. 

Nucleosides are much more water-soluble than the free bases because of the hydrophilicity of the sugar moiety. Like glycosides (see Chapter 7), nucleosides are relatively stable in alkali. Pyrimidine nucleosides are also resistant to acid hydrolysis, but purine nucleosides are easily hydrolyzed in acid to yield the free base and pentose. 

RNA is relatively resistant to the effects of dilute acid, but gentle treatment of DNA with 1 mM HCl leads to hydrolysis of purine glycosidic bonds and the loss of purine bases from the DNA. The glycosidic bonds between pyrimidine bases and 2 -deoxyribose are not affected, and, in this case, the polynucleotide s sugar-phosphate backbone remains intact. The purine-free polynucleotide product is called apurinic acid. 

Dondoni has elaborated this methodology to include C-glycosylated dihydro-pyrimidines/ The sugar residue can be a subunit in the aldehyde, 1,3-dicarbonyl, or urea consequently, substitution of the DHPM ring may occur in one of three places depending on which component originally contains the glycosidic residue. In the example... 

Replacement of heterocyclic rings in nucleosides by ring systems which do not occur in nature represents another approach to compounds which may have activity against viral and neoplastic diseases. One of the early successes in this category involves replacement of a pyrimidine ring by a triazine. The synthesis starts with a now classical glycosidation of a heterocycle as its silylated derivative (146) with a protected halosugar (145), in this case a derivative of arabinose... 

Most nucleosides contain D-ribose or 2-deoxy-D-ribose linked to N-1 of a pyrimidine or to N-9 of a purine by a P-glycosidic bond whose syn conformers predominate. 

Figure 35-1. A segment of one strand of a DNA molecule in which the purine and pyrimidine bases guanine (G), cytosine (C), thymine (T), and adenine (A) are held together by a phosphodiester backbone between 2 -de-oxyribosyl moieties attached to the nucleobases by an W-glycosidic bond. Note that the backbone has a polarity (ie,a direction). Convention dictates that a single-stranded DNA sequence is written in the 5 to 3 direction (ie, pGpCpTpA, where G, C,T, and A represent the four bases and p represents the interconnecting phosphates).

Davoll, J., Lythgoe, B., Todd, A.R. (1946) Experiments on the Synthesis of Purine Nucleosides. Part XII. The Configuration of the Glycosidic Centre in Natural aud Syuthetic Pyrimidine and Purine Nucleosides. Journal of the Chemical Society, 833-838. 

Hydrolytic cleavage of the glycosidic bond holding the DNA bases to the sugar-phosphate backbone is typically a very slow process under physiological conditions (pH 7.4 37°C). Loss of the pyrimidine bases cytosine and thymine occurs with a rate constant of 1.5 X 10 s (ty2 = 14,700 years), while loss of the purine bases guanine and adenine proceeds slightly faster, with a rate constant of 3.0 X... 

C5 , then the atom is said to be endo, and if it is on the opposite side it is defined as exo. The conformation about the sugar-base linkage is defined as anti when the torsion angle (chi, 04 -Cl -Nl -C2 for pyrimidines and 041-Cl -N9-C4 for purines) lies near 180° and syn when it lies near 0°. These situations are illustrated in Figure 22. The glycosidic linkage are all anti in B-DNA and A-DNA, but in Z-DNA the guanine bases are in the syn conformation. 

Figure 1.42 The three pyrimidine bases common to nucleic acid construction. Cytosine and thymine are found in DNA, while in RNA, uracil residues replace thymine. The associated sugar groups are bound in N-glycosidic linkages to the N-l nitrogen.

Those nucleosides found in the nucleic acids DNA and RNA involve the joining of ribose of deoxyribose to a purine or a pyrimidine base. One such nucleoside is adenosine, in which a nitrogen of adenine is linked to carbon 1 of the pentose, ribose. In this form it is a component of RNA but as a phosphory-lated derivative of adenosine (e.g. ATP), which is a high energy compound, it fulfils an important role in metabolism. The dinucleotides NAD and NADP are two cofactors necessary for many enzymic transformations and these also contain /V-glycosides of ribose phosphate. Other important nucleosides are found... 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

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