Nucleosides chemical syntheses

Recent developments in DNA/RNA chemical synthesis have allowed us to attach some functional groups covalently to nucleic acids, thus permitting the introduction of a functionality or properties not normally present in the native biomolecule The use of non-nucleosidic linkers is probably the most popular approach for the 5 -terminal modification of chemically synthesized nucleic acid oligonucleotides and a number of such linkers are commercially available. The linker shown in Fig. 2 is designed as a phosphoramidate derivative so that it can be incorporated into the 5 -terminus of the sequence as the last... 

The only general approach to the chemical synthesis of glycosyl esters of nucleoside pyrophosphates thus far found useful involves... 

Methods of Chemical Synthesis of Amino Acid and Peptide Esters of Nucleosides, Nucleotides, and Oligonucleotides T. L. Tsilevich, A. A. Kraevskii and B. P. Gottikh, Russ. Chem. Rev. (Engl. Transl.), 1972, 41, 822-832. 

Figure 15.2 Spin-labeled nucleosides that have been incorporated into nucleic adds during chemical synthesis of the oligomer. In structures 4 and 5, X is either H or OH.

Interestingly enough, 1/3-n-ribofuranosyl thy mine represents, thus far, the only pyrimidine nucleoside whose chemical synthesis had been achieved, and whose detailed structure was known, prior to its isolation from natural sources. 

As a direct result of these anhydronucleoside studies, methods have been developed126,262 for the chemical synthesis of 2-deoxynucleosides of pyrimidines. It was noted126 that the 2-O-tosyluridine derivative LXXXVI, when caused to react with sodium iodide in hot 2,5-hexanedione (acetonylace-tone), is converted into a 5-0-acetyl-2-deoxy-2-iodo nucleoside which, upon reduction under alkaline conditions, yields 2-deoxyuridine (V, R = H). In analogous fashion, the 5-O-acetyl derivative of l-/S-D-ribofuranosyl-thymine68 is converted by sodium iodide to CVI which, after deacetylation followed by reduction in the presence of palladium catalyst, yields thymidine (V, R = CH,).126... 

Scheme 37 Second and third stages of the evolution of amino acid activation (2) The system of Scheme 39 is improved by enzyme catalysis the mixed anhydride is stabilized by binding making the equilibrium with NCA more favorable (3) an alternative pathway for nucleoside triphosphate synthesis has been introduced, the chemical flux has been reverted...

The chemical synthesis of RNA has the distinct advantage of allowing for site-selective incorporation of modified nucleosides into the oligonucleotide chain. The early phosphodi-ester method developed by Khorana (30) was followed by the H-phosphonate and phosphoramidite approaches (31). Although the H-phosphonate approach has distinct advantages over phosphoramidite synthesis, it is not as widely used. Therefore, the focus of this section will be on the more commonly employed... 

Many eucaryotic phenylalanine transfer ribonucleic acids (tRNA ) contain fluorescent components at the position adjacent to the 3 -end of an anticodon. A few related hypermodified nucleosides 1 have been isolated, their structure has been elucidated, and their chemical synthesis been performed. 

The chemical synthesis of a sugar nucleotide diphosphate makes use of an activated nucleotide monophosphate [23] and a glycosyl monophosphate. The most efficient nucleoside monophosphates are phosphorimidazolidates... 

Chemical Synthesis.—Two new methods for 5 -phosphorylation of nucleosides have been described. In the first, phosphorous acid and mercuric chloride are heated at 80 °C in iV-methylimidazole, and a 2, 3 -0-isopropylidene-protected nucleoside is added. On work-up the 5 -phosphate is obtained in 60— 70% yield. The phosphorylating agent is presumed to be an iV-phosphoryl-AT -methylimidazolium species (1). The second method employs tris-(8-quinolyl)... 

Chemical Synthesis.—The phosphorimidazolidate method for the preparation of nucleoside di- and tri-phosphates has been re-examined and extended. For instance, ATP may be prepared either by activating ADP with carbonyl di-imidazole and treating the resulting phosphorimidazolidate with inorganic... 

Whether the glycosyl ureides play a role in normal metabolic processes remains a challenging question. The fact that the chemical synthesis of pyrimidine nucleosides from glycosyl ureides has been demonstrated should serve to stimulate further investigation of this problem, particularly with the application of some of the more recent, sensitive techniques including radioactive tracers and paper chromatography. ... 

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