Nucleosides review

For recent fluorinated nucleosides reviews, see (a) Meng, W-D. and Qing F-L. (2006) Fluori-nated nucleosides as antiviral and antitumor agents. Current Topics in Medicinal Chemistry, 6, 1499-1528 (b) Qing, F-L. and Qiu, X-L. (2007) Synthesis of gem-difluoromethylated sugar nucleosides. In Current Fluoroorganic Chemistry, ACS Symposium Series 949, pp. 305-322 and references cited therein. 

The present review complements and concludes the first part [97-AHC(68)223], which was devoted to the chemistry of C-nucleosides of hetero monocyclic bases. C-Nucleosides reviewed in this part were systematized according to the size and complexity of the base component, starting with those of simpler base components followed by more complex ones. Within a class of a particular base component, the arrangement also goes from less to more complex attached components. The C-nucleosides of a certain category are discussed first, followed by their analogs in the sequence homo, carbocyclic, reverse, and acyclo C-nucleosides [for definitions, see Part I, 97AHC(68)223]. To avoid redundancy, whenever the synthesis of a C-nucleoside of a condensed base comprised the elaboration of a C-nucleoside of a monocyclic base, the synthesis of the latter is usually not discussed, since it has already been mentioned in the first part of this review. The literature has been surveyed to Vol. 125, No. 7 (1996), of Chemical Abstracts and Vol. 142 No. 10 (1996), of the Index Chemicus. 

Sulfenamides, R2NSR, prepared from an amine and a sulfenyl halide, are readily cleaved by acid hydrolysis and have been used in syntheses of peptides, penicillins, and nucleosides. They are also cleaved by nucleophiles and by Raney nickel desulfurization." The synthesis and application of sulfenamides have been reviewed. ... 

The use of this group in nucleotide and nucleoside synthesis has been reviewed. ... 

Trost and co-workers have explored asymmetric transidon metal-catalyzed allylic alkyla-dons. Details on this subject have been well reviewed by Trost and others. With the use of asymmetric palladium-catalyzed desymmetrizadon of meso-2-ene-l,4-diols, cii -l,4-dibenzoy-loxy-2-cyclopentene can be converted to the enandometrically pure cii -4-rfirr-butoxycar-bamoyl-l-methoxycarbonyl-2-cyclopentene. The product is a usefid and general building block for synthesis of carbocyclic analogs of nucleosides as presented in Scheme 5.12. 

De Clercq E, Descamps J, De Somer P, Holy A (1978) (S)-9-(2,3-Dihydroxypropyl)adenine an ahphatic nucleoside analog with broad-spectrum antiviral activity. Science 5 563-565 De Clercq E, Holy, A (2005) Acyclic nucleoside phosphonates a key class of antiviral drugs. Nature reviews 4 928-940... 

Nucleoside and nucleotide reverse transcriptase analogues (NRTI) lack a 3 hydroxyl group and as a result no additional nucleotides can be incorporated into the growing DNA chain. Two NRTI resistance mechanisms are identified impairment of the incorporation of the antiretroviral drug (discrimination) and removal of the analogue from the terminated DNA chain (excision) as reviewed in Chap. 3 (Arion et al. 1998 Meyer et al. 1999 Saralianos et al. 1999). 

A. Mononucleotides.—A new journal has appeared in the past year consisting of abstracts of papers published in the nucleotide and nucleic acid fields. The use of nucleosides and nucleotides as potential therapeutic agents has been reviewed. Nucleotides which have been prepared recently using conventional methods of phosphorylation include those derived from 6-methylthiopurine ribonucleoside (la), 5-methylsulphonyluridine (lb), l-(jS-D-ribofuranosyl)-2-pyrimidone (Ic), 3-(jS-D-ribofuranosyl)-4-pyrimidone (Id), and various thionucleosides. - O-Phosphorylated 3 -amino-3 -deoxythymidine (2a) and 5 -amino-5 -deoxythymidine (2b)... 

C. Oligo- and Poly-nucleotides.—The stepwise enzymatic synthesis of internucleotide bonds has been reviewed. A number of polynucleotides containing modified bases have been synthesised " in the past year from nucleoside triphosphates with the aid of a polymerase enzyme, and the enzymatic synthesis of oligodeoxyribonucleotides using terminal deoxynucleotidyl transferase has been studied. Primer-independent polynucleotide phosphorylase from Micrococcus luteus has been attached to cellulose after the latter has been activated with cyanogen bromide. The preparation of insolubilized enzyme has enabled large quantities of synthetic polynucleotides to be made. The soluble enzyme has been used to prepare various modified polycytidylic acids. ... 

An early review on the template-directed synthesis of oligonucleotides using imidazo-lides of nucleoside S -phosphate is included in reference 153]. 

The review articles by Schramm (1998, 2003) provide a number of examples of the successful application of this protocol to the design of enzyme-specific transition state-like inhibitors. Among these, the transition state inhibitors of human purine nucleoside phosphorylase (PNP) are particularly interesting from a medicinal chemistry perspective, as examples of these compounds have entered human clinical trials for the treatment of T-cell cancers and autoimmune disorders. 

Adenosine metabolism (Fig. 12.2) is reviewed in Dunwiddie Masino (2001) and Ribeiro et al. (2002). The phosphorylation of intracellular adenosine to AMP is catalyzed by adenosine kinase. Intracellularly, adenosine can also be deami-nated to inosine by adenosine deaminase. Free intracellular adenosine is normally low. Excess adenosine, which cannot be regenerated to ATP, is extruded to the extracellular space by equilibrative nucleoside transporters (ENTs) in the cell membrane. During electrical stimulation or energy depletion, adenosine is... 

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

In the U.S.A. various pyridazine analogues of naturally occurring pyrimidine nucleosides have been prepared [299, 300] for a review on this subject see [13]. Within this series, 3-deaza-6-azauridine (86) has been found to inhibit the growth of L-1210 mouse leukaemic cells with an ID50 value of a 7 X 10 5 M [299, 301], The inhibitory effect of this uridine isoster might be due to interference in pyrimidine biosynthesis [302],... 

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