2 -Amino-2 -deoxycytidine

The synthesis of a 2 -amino-2 -deoxyuridine 168 and a 2 amino-2 deoxycytidine 169 from inexpensive uridine has been described. A key transformation in the synthesis is the introduction of an amino functionality via a trichloroacetimidate. This approach also avoids the use of azide that is not desirable for large-scale use (Scheme 8.48). 

Prusoff WH, Chen MS, Fischer PH, Lin TS, Shiau GT, Schinazi RF, Walker J (1979) Antiviral iodinated pyrimidine deoxyribonucleosides 5-iodo-2 -deoxyuridine 5-iodo-2 -deoxycytidine 5-iodo-5 -amino-2, 5 -dideoxyuridine, Pharmacol Ther 7 1-34... 

Deamination, the hydrolytic loss of exocyclic amino groups on the DNA bases, is typically a very slow reaction. For example, deamination of cytosine residues in dnplex DNA occnrs with a half-life of about 30,000 years under physiological conditions, and the deamination of adenine residues is still more sluggish. " Alkylation at the N3-position of cytosine (Scheme 8.5) greatly increases the rate of deamination (ty2 = 406 h). Deamination of 3-methyl-2 -deoxycytidine proceeds 4000 times faster than the same reaction in the unalkylated nucleoside. Alkylation of the N3-position in cytosine residues also facilitates deglycosylation (Jy2 = 7700 h, lower pathway in Scheme 8.5), but the deamination reaction is 20 times faster and, therefore, predominates. ... 

Some other interesting observations regarding free radicals in these systems are noteworthy. In many instances, multiple conformations of radicals are found at lower but not higher temperatures. This indicates that the radicals exist in shallow energy wells at low temperature this phenomenon was observed very early, in the 4 K ENDOR investigation of radical formation in amino acids.23 Unlike the process in DNA. In which it is well understood that the thymine anion radical protonates at C6 to form T(C6)H-, in the crystalline state there is a not clear link between pyrimidine electron adducts and H-addition radicals. We finally note that a deuterium isotope effect of protonation/deprotonation processes was found in cytosine.HCl and 2 -deoxycytidine.HCl, as evidenced by a lower propensity for these processes to occur in partially deuterated systems than in predated ones. 

A phosphorylase from Escherichia coli has been purified it is specific for 2-deoxy-D-ribosyl phosphate, but can use uracil, 2-thiouracil, 5-amino-uracil, 5-bromouracil, and 2-thiothymine as a pyrimidine. Deaminases of adenosine, 2-deoxyadenosine, cytidine, and 2-deoxycytidine have been detected in Escherichia coli. 

However, that model system did not provide final evidence as it suffered from the presence of amino substituent instead of alkoxy group attached to the phosphorus atom. Fortunately, the /asf-eluting diastereomer of 5 -0-DMT-iV4-ben-zoyl deoxycytidine-3 -0-(2-thio-4,4-dimethyl-l,3,2-oxathiaphospholane) (14, B =CytBz) after detritylation with p-toluenesulfonic acid, yielded AT1-benzoyl de-oxycytidine-3 -0-(2-thio-4,4-dimethyl-l,3,2-oxathiaphospholane) (20) which... 

Difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoic acid 4,ll-bis[(2-Aminoethyl)amino]anthra[2,3-b]furan-5,10-diones 4(l-Anilino-podophyllotoxin derivatives 5-Aza-2 -deoxycytidine 5-Bromotetrandrine 5-Cyclohexylindolyl-2 -deoxyribose (non-natural nucleoside) 5 -Fluorosulfonylbenzoyl 5 -adenosine 5-Fluorouracil 5,5-Diphenylbarbituric acid 6-[(2S,4R,6E)-4-Methyl-2-(methylamino)-3-oxo-6-octenoic acid] cyclosporine D (PSC833) 6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid 6-Mercaptopurine 6-Prenylchrysin 6-Thioguanine 6,7-Dimethoxy-... 

Crosslinking of DNA and proteins is a versatile method to study protein-DNA interactions. Among others, phosphoramidites of brominated or iodinated 2 -deoxycytidines [325], 2 -desoxuridines [326,327] and recently also of 2 -deoxyadenosines 132 have been used [328]. Nucleophilic replacement of the bromine by an amino group during deprotection does not occur when reaction conditions of concentrated ammonia solution for 24 h at room temperature are used after oligonucleotide synthesis. 

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