Thymine reaction with

Removal of the 2 -sulfonyloxy group of 859 in a basic medium, followed by reaction with metal halides (LiBr and Nal) or hydrogen halides (HCl-1,4-dioxane, HBr-acetone, or0.1% HFin l,4-dioxane-AlF3)gave, byway of the 2,2 -anhydro intermediate 861, the 2 -halo derivatives 862-865. The 2 -deoxy analog 866 and l-(6-deoxy-6-fluoro- ff-D-mannopyranosyl)thy-mine were also prepared from 864 (R = H) and 861 (R = H), respectively. l-(4-Deoxy-4-fluoro-y -D-glucopyranosyl)thymine was obtained by the condensation method. A different kind of nucleoside, 5-(5-deoxy-5-fluoro-2,3-0-isopropylidene-a-D-ribofuranosyl)-l,3-dimethyluracil has also been prepared. ... 

Addition of a radical to the C6-position of thymine residues in DNA generates the C5-thymine radical 74 (Scheme 8.27). Reaction with molecular oxygen, followed by reduction, yields the hydroperoxide 75. Decomposition of the hydroperoxide ultimately yields the hydantoin nucleobase 78 via the ring-opened derivatives 76 and 77 ti,2 for the decomposition of 75 in aqueous solution is slow, with a 9 h for the tra i-isomer and 20 h for the c -isomer of the nucleoside)... 

Finally a few sentences are deserved for the vast area of DNA photochemistry. Thymine dimerization is the most common photochemical reaction with the quantum yield of formation in isolated DNA of all-thymine oligodeoxynucleotides 2-3% [3], Furthermore, a recent study based on femtosecond time-resolved transient absorption spectroscopy showed that thymine dimers are formed in less than 1 ps when the strand has an appropriate conformation [258], The low quantum yield of the reaction in regular DNA is suggested to be due to the infrequency of these appropriate reactive conformations. 

Interestingly, one-electron oxidants partly mimic the effects of OH radicals in their oxidizing reactions with the thymine moiety of nucleosides and DNA. In fact, the main reaction of OH radicals with 1 is addition at C-5 that yields reducing radicals in about 60% yield [34, 38]. The yield of OH radical addition at C-6 is 35% for thymidine (1) whereas the yield of hydrogen abstraction on the methyl group that leads to the formation of 5-methyl-(2 -de-oxyuridylyl) radical (9) is a minor process (5%). Thus, the two major differences in terms of product analysis between the oxidation of dThd by one-electron oxidants and that by the OH radical are the distribution of thymidine 5-hydroxy-6-hydroperoxide diastereomers and the overall percentage of methyl oxidation products. 

An analogous series of reactions is used to produce depyrimidinated DNA fragments. Hydrazine is used in these reactions, since both cytosine and thymine react with hydrazine. The bases are cleaved to yield urea and a pyrazole ring. The deoxyribose moiety is left as a hydrazone. Piperidine, which reacts with the hydrazone, is used to cleave the nucleotide chain. Cytosines react specifically with hydrazine in 5 mol/ L NaCl, but no specific reaction exists for thymines. Consequently, one aliquot yields labeled oligonu-cleotides 3 -terminated at cytosines, whereas a second aliquot contains nucleotides cleaved in the absence of NaCI at both cytosine and thymine residues. 

Figure 2 Double-stranded oligonucleotide photoprobes that simulate modified DNA and intended to cross-link to DNA-binding proteins. (A) Probe modeling interstrand cross-linking by cisplatin Source From Ref. [63], with permission from the American Chemical Society via the Rightslink service (license number 2458870278307 granted June 30, 2010). The benzophenone probe prior to reaction with DNA is shown in the lower part of the panel. (B) Photoaffinity probe for bacterial DNA repair proteins. TT is a simulated thymine dimer intended to be recognized as a site of damage in DNA, and T (two instances) is the diazirine thymine derivative T Source From Ref. [64], with permission from Wiley.

Oxygen-free reactions of psoralens, when in close proximity to the target, proceed via the first excited states in which the 3,4-and the 4, 5 7r-bonds of the pyrone and furan moieties, respectively, can undergo C4-cyclization reactions with, e.g., unsaturated bonds of lipids, or the C5=C6 double bonds of thymine in DNA. In reactions with DNA the psoralen is believed to intercalate with DNA in the dark. Subsequent irradiation at 400 nm usually leads to furan-side 4, 5 -monoadduct formation, whereas irradiation at 350 nm increases the formation of crosslinks in which the furan and pyrone rings form C4 cycloadducts to thymines on opposite strands [95], Subsequent irradiation of the 4, 5 -monoadducts at 350 nm leads to formation of crosslinks and conversion into pyrone-side 3,4-monoadducts. Shorter wave-... 

Thymine also undergoes a photoaddition reaction with water to form the anti-Markovnikov product ... 

The pyrimidines cytosine and thymine both react with hydrazine, which initially attacks the unsaturated carbonyl system and then leads to ring opening. Again, base treatment is used to hydrolyse the phosphodiester bond. This reaction becomes selective for cytosine in the presence of NaCl, which suppresses reaction with thymine. 

With unsubstituted 5-iodouracil 336, a trimagnesiated species 337 can be formed by sequential treatment with methylmagnesium chloride and isopropylmagnesium chloride, and reaction with various electrophiles then selectively gives 5-functionalized uracil derivatives 338 <20070L1639>. The same procedure was also successfully applied to the functionalization of 6-iodouracils, including the synthesis of Emivirine and l-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (ElEPT) precursors <20070L1639>. 

An unusual photochemical reaction of 2-pyridones, 2-aminopyridinium salts and pyran-2-ones is photodimerization to give the so-called butterfly dimers. These transformations are outlined in equations (13) and (14). Photodimerization by [2+2] cyclization is also a common and important reaction with these compounds. It has been the subject of particular study in pyrimidines, especially thymine, as irradiation of nucleic acids at ca. 260 nm effects photodimerization (e.g. equation 15) this in turn changes the regular hydrogen bonding pattern between bases on two chains and hence part of the double helix structure is disrupted. The dimerization is reversed if the DNA binds to an enzyme and this enzyme-DNA complex is irradiated at 300-500 nm. Many other examples of [2+2] photodimerization are known and it has recently been shown that 1,4-dithiin behaves similarly (equation 16) (82TL2651). 

Samuelsson, L. and LangstrOm, B., Synthesis of l (2 deoxy-2 -fluoro-(3-D-arabinofuranosyl)-[Me thy l-nc]Thymine ([nc]Fmau) via a Stille cross-coupling reaction with [nc]Methyl Iodide, J. Labelled Compd ... 

In 2005, the Kinugasa reaction performed on /V-propargyl nucleobases, such as adenine, uracil, and thymine derivatives, with diphenyl nitrone has been reported to produce cis- and trans-(3-lactam nucleosides (Scheme 63), [157]. 

The reaction of thioketones with any compound with an activated double C=C bond leads to the formation of a thietane. Friedel et al. <20050BC1937> performed the photoreaction of 1-substituted thymine 91 with thiobenzo-phenone, achieving the bicyclic thietane 92, but in a very poor yield (4%) (Equation 30). 

In Section III.B.2, the difficulties inherent in the use of insoluble unmodified heterocycles were described, together with some methods of overcoming this difficulty reported by Benneche and Undheim. This problem is also encountered in the field of uracils. Thus, the same authors reported the Pd(0)-catalyzed allylation of the bis-(O-trimethylsilyl) derivative of thymine (181) which gives directly the mono- and the bis-JV-allylated products 182 and 183 (Scheme 41). The same reaction with rac-160 affords rac-184, with overall retention of configuration (92ACS761). 

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