Nucleosides and derivatives

Trimethyloxonium tetrafluoroborate, 327 Nucleosides and derivatives Allyl chloroformate, 9... 

When substituted at N(9) as in nucleosides and derivatives, the purine bases offer two potential metal ion binding sites. In neutral solutions of adenosine both N(l) and N(7) deprotonate while with the 6-oxopurines inosine and guanosine only N(7) deprotonates. N(1)H deprotonations occur with pK values of 3,6, 8.7, and 9.2 in adenosine, inosine, and guanosine, respectively... 

These conclusions are Illustrated in Figure 3 for some representative compounds. They are compatible with the FMR data of more than 60 nucleosides and derivatives.We deduce from this an obligatory Intramoleciilar structure stabilization in all nucleosides which contain in jxixtaposltlon polar or ionic 5 -substituents and heterocycles with an asymmetric electron density distribution the vast majority of natural nucleotides, nucleoside antibiotics, etc., are built in that way. 

The application of coupled oscillator and related theories to the investigation of nucleic acids and polynucleotides has been reviewed by Brahms. The optical activities of single nucleosides and derivatives have been calculated by a coupled oscillator theory in which the tt-tt transitions of the bases were decomposed into individual bond-bond transition moments which were then coupled by the dipolar coupling mechanism. Apparently such a treatment was necessary to account for deficiencies in the simple approach of chromophore-centered dipole transition moments. 

Nucleotides are phosphoric acid esters of nucleosides Those derived from adenosine of which adenosine 5 monophosphate (AMP) is but one example are especially promi nent AMP is a weak diprotic acid with s for ionization of 3 8 and 6 2 respectively In aqueous solution at pH 7 both OH groups of the P(0)(0H)2 unit are ionized... 

Section 28 2 Nucleosides are carbohydrate derivatives of pyrimidine and purine bases The most important nucleosides are derived from d ribose and 2 deoxy D ribose... 

A two-component sugar-base unit is called a nucleoside, eg, adenosine. Nucleosides and their derivatives are important pharmaceutically (see Antibiotics, NUCLEOSIDES AND NUCLEOTIDES ANTIVIRAL AGENTS). 

Uracil reacts with hydrazine to give pyrazol-3(2if)-one (944) and urea N-methyl- and dimethyl-hydrazine behave similarly to give the 2-methyl- and 1,2-dimethyl derivatives. The reactions of hydrazines with uridine and related nucleosides and nucleotides is well studied (67JCS(C)1528). The tautomerism and predominant form of uracil are discussed in Section 2.13.1.8.4. 

These were originally prepared by Khorana as selective protective groups for the 5 -OH of nucleosides and nucleotides. They were designed to be more acid-labile than the trityl group because depurination is often a problem in the acid-catalyzed removal of the trityl group. Introduction of p-methoxy groups increases the rate of hydrolysis by about one order of magnitude for each p-methoxy substituent. For 5 -protected uridine derivatives in 80% AcOH, 20°, the time for hydrolysis was... 

This group was developed for protection of the 5 -OH group in nucleosides. The derivative is prepared from the corresponding triaiylmethyl chloride, and is cleaved by reductive cleavage (Zn/AcOH) of the phenacyl ether to the p-hydroxyphenyl-diphenylmethyl ether followed by acidic hydrolysis with formic acid. ... 

The triphenylmethoxyacetate was prepared in 53% yield from a nucleoside and the sodium acetate (Ph3C0CH2C02Na, i-Pr3C6H2S02Cl, Pyr) as a derivative that could be easily detected on TLC (i.e., it has a distinct orange-yellow color after it is sprayed with ceric sulfate). It is readily cleaved by NH3/MeOH (100% yield). ... 

The most important nucleosides are derived from D-ribose and 2-deoxy-D-ribose. 

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). 

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)... 

Lewis, M. A. Graff Yoerg, D. Bolton, J. L. Thompson, J. A. Alkylation of 2 -deoxy-nucleosides and DNA by quinone methides derived from 2,6-di-tert-butyl-4-methyl-phenol. Chem. Res. Toxicol. 1996, 9, 1368-1374. 

Figure 27.1 Three common nucleoside triphosphate derivatives that can be incorporated into oligonucleotides by enzymatic means. The first two are biotin derivatives of pyrimidine and purine bases, respectively, that can be added to an existing DNA strand using either polymerase or terminal transferase enzymes. Modification of DNA with these nucleosides results in a probe detectable with labeled avidin or streptavidin conjugates. The third nucleoside triphosphate derivative contains an amine group that can be added to DNA using terminal transferase. The modified oligonucleotide then can be labeled with amine-reactive bioconjugation reagents to create a detectable probe.

Phenylglyoxal and alkoxyphenylglyoxals react selectively with the guanine moiety of nucleosides and nucleotides in phosphate buffer (pH 7.0) at 37°C for 5-7 min to give the corresponding fluorescent derivatives [12-15], as shown in Figure 6. Other nucleic acid bases and nucleotides (e.g., adenine, cytosine, uracil, thymine, AMP, CMP) do not produce derivatives under such mild reaction conditions. The fluorescent derivative emits chemiluminescence on oxidation with di-methylformamide (DMF) and H202 at pH 8.0-12 [14, 15],... 

The nitrile group in 82 has been transformed into other versatile functional groups, and the derivatives so obtained have been used in the synthesis of various naturally occurring C-nucleosides and their analogs. Reduction of 82 with lithium aluminum hydride gave the amine 90 which was, in turn, transformed84 into the ureido and N-ni-troso derivatives (91-93) by treatment with nitrourea, followed by benzylation, and nitrosation.85 The diazo derivative 94, obtained by treatment of 93 with alcoholic potassium hydroxide, was a key intermediate in the synthesis of formycin B and oxoformycin B (see Section III,2,a,b). 

Reverse transcriptase inhibitors are of two types those that are derivatives of purine- and pyrimidine-based nucleosides and nucleotides (NtRTIs) and those that are not nucleoside or nucleotide based (NNRTIs). 

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