Nucleosides pyrimidines

The anomeric carbon is attached to N 1 in pyrimidine nucleosides and to N 9 in purines... 

Aminohexose Nucleosides. The 4-aminohexose nucleosides (128—140) are Hsted in Table 7 (1—4,240—242). A biosynthetic relationship between the 4-aminohexose peptidyl nucleoside antibiotics and the pentopyranines has been proposed (1). The 4-aminohexose pyrimidine nucleoside antibiotics block peptidyl transferase activity and inhibit transfer of amino acids from aminoacyl-tRNA to polypeptides. Hikizimycin, gougerotin, amicetin, and blasticidin S bind to the peptidyl transferase center at overlapping sites (243). 

Basically, AZT is anabohcaHy phosphorylated to AZT mono-, di-, and tri-phosphates by various enzymes (kinases) of a target ceU (159). AZT-triphosphate competes with other phosphorylated pyrimidine nucleosides for incorporation into HIV DNA by the viral reverse transcriptase. Incorporation of the AZT-triphosphate into reverse transcriptase results in viral DNA chain termination. Reverse transcriptase is essential in the repHcative cycle of HIV. 

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. 

C-Alkenylation of pyrimidine nucleosides and their analogs 99UK532. 

The bromide (5) failed to couple with dialkoxypyrimidines, even at elevated temperatures the failure is probably because of steric conditions imposed by the axially oriented C-4 p-nitrobenzoyloxyl group (see structure 5) this same group in the other halides (la, lb, 2a, 2b, 4a, and 4b) discussed in the foregoing is an equatorial substituent. Accordingly, the preparation of a differently constituted halide of 2-deoxy-D-Zt/xo-hexose is being investigated for the synthesis of pyrimidine nucleosides. 

Another deviation from the normal displacement reaction of primary tosylates occurs in nucleoside derivatives (39, 81) where cyclonucleosides and anhydronucleosides are formed by participation of a nitrogen atom (as in purine nucleosides) and oxygen atom (as in pyrimidine nucleosides ), respectively. Iodonucleosides can result from these reactions only if these cyclic compounds are prone to attack by iodide ion. Several new examples of unexpected reactions during the solvolysis of sulfonate esters in sugar derivatives have been recorded in the past few years (2, 4,5,7,15,44,62,63,94). 

Azacitidine (5-aza-cytidine, Fig. 8) is a pyrimidine nucleoside analog of cytidine. The structural formula is... 

Degrfeve B, De Clercq E, Balzarini J (1999) Bystander effect of purine nucleoside analogues in HSV-1 tk suicide gene therapy is superior to that of pyrimidine nucleoside analogues. Gene Ther 6 162-170... 

Examples involving the use of organomercury reagents as nucleophiles in aqueous media are also known. Bergstrom studied the synthesis of C-5-substituted pyrimidine nucleosides in aqueous media via a mercurated intermediate using Li2PdCl4 as a catalyst (Eq. 6.42).136... 

Balzarini J, Perez-Perez M-J, San-Felix A, Velazquez S, Camarasa M-J, De Clercq E. [2, 5 -Bis-0-(tert-Butyldimethylsilyl)]-3 -spiro-5"- [4"-amino-1",2"-oxathiole-2",2"-dioxide) (TSAO) derivatives of purine and pyrimidine nucleosides as potent and selective inhibitors of human immunodeficiency virus type 1. Antimicrob Agents Chemother 1992 36 1073-1080. 

Fig.n.2. Human duodenal expression variability of nucleoside, organic cation ion, and anion transporters (unpublished data). Shaded box indicates 25-75% of expression range, the line within the box marks the median, and error bars indicate 10-90% of expression range. ENT2, equilibrative nucleoside transporter CNT1, concentrative pyrimidine nucleoside transporter CNT2, concentrative purine nucleoside transporter ... 

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