Nucleoside derivatives acids

The potentialities of this method are such that, with the proper choice of hexofuranose derivative, access can be gained to 2,5-anhydroaldoses in which the side chains have the cis orientation, as would be required for further elaboration into C-nucleosides. Matsui and coworkers62 reported the synthesis of modified C-nucleosides by acidic treatment of 3-0-benzyl-l,2-0-isopropylidene-5,6-di-0-(methylsulfonyl)-/3-L-talofuranose (60), to give 2,5-anhydro-3-0-benzyl-6-0-(methylsulfonyl)-aidehydo-D-allose dimethyl acetal (61). 

Bi analogues. Also omitted are the phosphorothioic acid derivatives, such as the insecticide diazinon, and related compounds. Unnatural nucleoside derivatives have been given only brief mention, since the base, rather than the sugar, is our target in this review. 

In biological methylation, the 5-methyl group of the amino acid L-methionine is used to methylate suitable O, N, S, and C nucleophiles. First, methionine is converted into the methylating agent S-adenosylmethionine (SAM). SAM is nucleoside derivative (see Section 14.3). Both the formation of SAM and the subsequent methylation reactions are nice examples of biological Sn2 reactions. 

An extension of this methodology was used In another approach (16) to the octosyl acids and ezomyclns (Figure 10). In this sequence, D-galactose was transformed Into the 2-0-acetyl derivative 57. Transformation to the acyclic nucleoside derivative and selective oxidation then gave sulfoxide 58. Elimination afforded the trans olefin 59 whereupon solvolysis followed by epoxldatlon and acid-catalyzed cycllzatlon produced and In a 1 2 ratio respectively. The H-NMR spectra showed each to contain a l, 2 -trans configuration, and that the minor Isomer was the required 6-D-nucleoslde, while the major product was the a-D-nucleoslde. 

Fig. 7.16 LAN (Locked nucleic acid) nucleosides as conformationally constrained nucleoside-derived A3 AR antagonists...

III. The Structure of Pyrimidine Nucleosides Derived from Nucleic Acids.. . . 285... 

The term nucleoside was originally proposed by Levene and Jacobs in 1909 for the carbohydrate derivatives of purines (and, later, of pyrimidines) isolated from the alkaline hydrolyzates of yeast nucleic acid. The phosphate esters of nucleosides are the nucleotides, which, in polymerized forms, constitute the nucleic acids of all cells.2 The sugar moieties of nucleosides derived from the nucleic acids have been shown, thus far, to be either D-ribose or 2-deoxy-D-eri/fAro-pentose ( 2-deoxy-D-ribose ). The ribo-nucleosides are constituents of ribonucleic acids, which occur mainly in the cell cytoplasm whereas 2-deoxyribo -nucleosides are components of deoxypentonucleic acids, which are localized in the cell nucleus.3 The nucleic acids are not limited (in occurrence) to cellular components. They have also been found to be important constituents of plant and animal viruses. 

Elementary analyses indicated that the sugar moieties of pyrimidine nucleosides derived from deoxyribonucleic acid are also of the deoxypen-tosyl type. Early attempts to apply the hydrogenation procedure of Levene and LaForge60 were unsuccessful. It was generally assumed, however, that the sugar portion of the pyrimidine nucleosides of deoxyribonucleic acid is probably also of the 2-deoxy-D-ribosyl type. 

Togo and Yokoyama developed a general and efficient method for the synthesis of C-nucleosides employing radical coupling pathways.53 -b Several of these C-nucleosides have been synthesized by ionic pathways but they require many steps and suffer a lack of generality. The thiohydroxamates derived from pentose or 2-tetrahydrofuryl carboxylic acid, Scheme 31, gave the corresponding C-nucleoside derivatives 77 in the presence of an appropriate heteroaromatic compound.53b... 

As shown in Sec. I, uracils have represented, for more than 90 years, a class of compounds that continually attract organic chemists, biochemists, medicinal chemists, and photobiologists. Uracils were first detected as constituents of ribonucleic acids, from which they were prepared by hydrolysis. Nucleosides derived from uracil are called uridine, pseudouridine, and uridine phosphate, respectively. Recently, uracil moieties were detected in the antibiotic Tunicamycin (85JA7761). 

Takamatsu, S., Katayama, S., Hirose, N., et al. (2001) Radical deoxygenation and dehalogena-tion of nucleoside derivatives with hypophosphorous acid and dialkyl phosphites. Tetrahedron Lett., 42, 7605-7608. 

---