Directed nucleosidations

Jung and Castro prepared 2 -deoxyuridine 302 using this strategy [107]. Reaction of the potassium salt of ribal 303 with 2-methylthiopyrimidone 304 incorporated the base. 

Verbruggen protocol utilizes neighboring group participation to achieve stereocontrol in nucleosidation 

Jung and Sugimura s approach to stereoselective nucleosidation of 2 -deoxyribonuoleosides relies on intramolecular delivery of the base 

The tether directing strategies for C- and O-glycosylation are one subset of a much wider area of using the temporary connection for controlling the regio- and stereochemical outcome in the reaction of nucleophiles with an electrophilic substrate. Some examples of this form of tether-mediated S3mthesis will be illustrated with some applications to natural product synthesis [109]. 

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Amino-2 -deoxypurines. 2 -AmiQo-2 -deoxyadenosine (15) is a naturally occurring A[-nucleoside isolated from A.ctinomadura that shows antknycoplasmal activity (1,4). Adenosine is the direct precursor for its biosynthesis (30). 2 -Arnino-2 -deoxyguanosine (16), isolated from a strain of Enterobacter cloacae (1,4), shows the growth of HeLa S3 cells and Sarcoma 180 in vivo and has been tested for antibacterial activity. 

The phosphodiester units highlighted in yellow in (a) join the oxygens at 3 of one nucleoside to 5 of the next. By convention, the sequence is read in the direction that starts at the free CH2OH group (S ) and proceeds toward the free 3 OH group at other end. 

Nucleic acids are linear polymers of nucleotides linked 3 to 5 by phosphodi-ester bridges (Figure 11.17). They are formed as 5 -nucleoside monophosphates are successively added to the 3 -OH group of the preceding nucleotide, a process that gives the polymer a directional sense. Polymers of ribonucleotides are named ribonucleic acid, or RNA. Deoxyribonucleotide polymers are called deoxyribonucleic acid, or DNA. Because C-1 and C-4 in deoxyribonucleotides are involved in furanose ring formation and because there is no 2 -OH, only... 

The reaction has been extended (106) to the nucleoside field and provides a means for the direct iodination of suitably protected nucleosides. Thus treatment of 2,3-O-isopropylidene uridine (68) with tri-phenylphosphite methiodide in N,2V-dimethylformamide at room temperature afforded the corresponding crystalline 5-deoxy-5-iodo analog 69 in 77% yield. 

Add 0.25 ml of DMF (./V,iV-dimethylformamide) and 0.25 ml of TRI-SIL TBT reagent to the sample in a screw-cap septum vial. If TRI-SIL TBT reagent is not readily available, add 0.25 ml of acetonitrile and 0.25 ml of BSTFA reagent instead. Heat at 60° for at least 1 hour for ribonucleosides or for a minimum of 3 hours for deoxyribo-nucleosides. After cooling to room temperature, inject 1-2 /a 1 of the reaction mixture directly into the GC. The resulting derivatives have been reported to be stable for weeks if capped tightly and refrigerated.1... 

Decitabine (5-aza-deoxycytosine) is an analog of the nucleoside 2 -deoxycytidine. It is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and by inhibition of the enzyme DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. DNA hypomethylation is achieved at concentrations below those required to significantly inhibit DNA synthesis, which may promote restoration of function to genes associated with control of cellular differentiation and proliferation. Cytotoxicity in rapidly dividing cells may also result from covalent adducts between DNA methyltransferase and decitabine. 

Because synthesis of l-(2-deoxy-2-fluoro-)S-D-arabinofuranosyl)cytosine (744, FAC), an elementary arabino type of nucleoside having a growth-inhibitory effect against L 1210 leukemia in mice, through direct introduction of a fluorine atom in the 2 - up (arabino) position was difficult, compound 744 was prepared by condensation of trimethylsilylated A -acetylcytosine with 3-0-acetyl-5-(7-benzoyl-2-deoxy-2-fluoro-D-arabin-ofuranosyl bromide (742), which had been prepared by periodate oxidation of 6-0-benzoyl-3-deoxy-3-fluoro-D-glucofuranose (741). Similar condensa-... 

A method for the direct spectrophotometric determination of dinucleoside monophosphates has been developed which relies on changes in u.v. absorbance after enzymic hydrolysis. - Hydrolytic fission of the dinucleoside monophosphate with a phosphodiesterase causes a change in the u.v. absorbance of the solution allowing the 5 -nucleoside to be estimated. Addition of a phosphomonoesterase to the hydrolysate causes a further change in u.v. absorbance, allowing the 3-nucleoside to be estimated. 

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

Acceleration of the Template- and Metal-Directed Polycondensation of Nucleoside-5 -phosphoric Imidazolides by Acylation... 

Peon J, Zewail AH (2001) DNA/RNA nucleotides and nucleosides direct measurement of excited-state lifetimes by femtosecond fluorescence up-conversion. Chem Phys Lett 348 255... 

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