Cytosines 5,6-dihydro

The 5-aza analog of cytosine could be taken as 4-amino-2-oxo-l,2-dihydro-1,3,5-triazine (40) which was prepared by the reaction of... 

Other degradation products of the cytosine moiety were isolated and characterized. These include 5-hydroxy-2 -deoxycytidine (5-OHdCyd) (22) and 5-hydroxy-2 -deoxyuridine (5-OHdUrd) (23) that are produced from dehydration reactions of 5,6-dihydroxy-5,6-dihydro-2 -deoxycytidine (20) and 5,6-dihydroxy-5,6-dihydro-2 -deoxyuridine (21), respectively. MQ-photosen-sitized oxidation of dCyd also results in the formation of six minor nucleoside photoproducts, which include the two trans diastereomers of AT-(2-de-oxy-/j-D-eryf/iro-pentofuranosyl)-l-carbamoyl-4 5-dihydroxy-imidazolidin-2-one, h/1-(2-deoxy-J8-D-crythro-pentofuranosyl)-N4-ureidocarboxylic acid and the a and [5 anomers of N-(2-deoxy-D-eryfhro-pentosyl)-biuret [32, 53]. In contrast, formation of the latter compounds predominates in OH radical-mediated oxidation of the pyrimidine ring of dCyd, which involves preferential addition of OH radicals at C-5 followed by intramolecular cyclization of 6-hydroperoxy-5-hydroxy-5,6-dihydro-2 -deoxycytidine and subsequent generation of the 4,6-endoperoxides [53]. 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

Stabilization of the (incipient) C 6) carbocation developing in the C-O heterolysis. The rate constants for the heterolysis reaction are a measure of the reducing power of 5,6-dihydro-6-methylpyrimidine-6-yl radicals. On this basis, the cytosine radicals are better reductants than the corresponding uracil radicals, and the radicals derived by hydrogen atom addition to pyrimidines are stronger reductants than those formed by OH radical addition [27]. 

The 5,6-double bond in uracil, 5-fluorouracil, /V-alkyluracils, thiouracils, and uridines adds sodium sulfite or bisulfite to give the corresponding 5,6-dihydro-6-sulfonic acid salts. Bisulfite addition to cytosines and cytidine may be succeeded by a second reaction involving nucleophilic replacement of the amino group, for example, by water. 

Hayon447 to absorb in this UV region. Similar measurements have been made for a number derivatives of uracil (5,6-dihydro, 1-, 3-, and 6-methyl, 1,3-dimethyl-, and 5-aminouracil, orotic acid, barbituric and isobarbituric acids also see similar measurements448 on 5-bromouracil and its iV-methyl derivatives), thymine itself and its derivatives (5,6-dihydro, 2-methylthymine). In the case of cytosine, Hayon447 has very tentatively suggested that species 47 and 48 are obtained on pulse radiolysis of the solution at pH 5.5, and 49 at pH 13.3. 

Both NER and BER forms of excision repair remove a great variety of defects, many of which are a result of oxidative damage.657 720 Most prominent among these is 7,8-dihydro-8-oxoguanine (8-OG), which is able to base pair with either cytosine (with normal Watson-Crick hydrogen bonding) or with adenine, which will yield a purine-purine mismatch and aC G —> A T transversion mutation (Eq. 27-24), a frequent mutation in human cancers.721 722... 

The electrolysis products in neutral medium included one additional absorbing substance, the chromatographic properties of which, together with its reaction with the Fink reagent to give a yellow product85), pointed to its being 5,6-dihydro-cytosine 86), further confirmed by its hydrolytic deamination to a product identical with 5,6-dihydrouracil. 

Another type of photochemical reaction involving a pyrimidine base is the addition of a molecule of water across the 5,6 double bond of C to yield a 5,6-dihydro-6-hydroxy derivative called the cytosine hydrate. The quantum yield for the formation of cytosine hydrates in UV-irradiated DNA is greater in single-stranded than in duplex-DNA (45). Hydrates of cytosine, deoxycytidine, CMP, or dCMP are unstable, readily reverting to the parent form by rehydration (45). However, their half-life is dramatically increased in DNA, and cytosine hydrate may be the major nondimer C photoproduct. Cytosine hydrate can undergo deamination and dehydration to yield uracil (1). The hydrate of 5-methylcytosine may undergo deamination to yield 5-thymine hydrate, which can convert to thymine upon dehydration (1). 

Hydration of the thymidine radical cation leads to the predominant formation of the oxidizing 6-hydroxy-5,6-dihydrothymid-5-yl radical whereas deprotonation mostly generates the methyl-centered radical (Fig. 4). As already pointed out, these two pyrimidine radicals are also produced upon reaction with OH. However, the methyl-centered radical represented only 5% of base radicals when produced by OH while it corresponds to 30% of the thymidine radicals produced upon one-electron oxidation. Type I photosensitization of 2 -deoxy-cytidine leads to the formation of the 6-hydroxy-5,6-dihydro-2 -deoxycytidil-5-yl radical also produced upon reaction with OH. Additional oxidative pathways involve the formation of 2-deoxyribonolactone and free cytosine as well as production of 2 -deoxyuridine as the result of deprotonation ofthe pyrimidine radical cation at Cl and NH2 group, respectively. 

Cyclization of cytidine (45a), cytosine (45c), or cytidine-5-phosphate (45d), with ethyl acetimidate gave the respective 5,6-dihydro-3-methyl-l,2,4-triazolo[4,3-c]pyrimidine-5-ones 51 (78MI1) (Scheme 22). 

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