1 - cytosine intramolecular

Although most of an RNA molecule is single-stranded, there often are some double-stranded regions. Intramolecular base pairing between guanine and cytosine and between adenine and uracil creates loops and kinks in the RNA molecule. The structure of one kind of RNA molecule is shown in Figure 13-30. 

The analogons deamination reaction is not observed in l-methyl-2 -deoxy-adenosine nncleosides. ° Rather, in the adenine series, the Dimroth rearrangement occnrs (Scheme 8.4). On the contrary, in styrene adducts of 2 -deoxyadenosine, the hydroxyl residue of the adduct undergoes intramolecular reaction with the base to initiate deamination (Scheme 8.6). ° ° Similarly, cytosine residues bearing styrene adducts at the N3-position undergo rapid deamination (nearly complete deamination is seen within 75h). °°... 

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]. 

Bansal KM, Patterson LK, Schuler RH (1972) Production of halide ion in the radiolysis of aqueous solutions of the 5-halouracils. J Phys Chem 76 2386-2392 Barnes JP, Bernhard WA (1994) One-electron-reduced cytosine in acidic glasses conformational states before and after proton transfer. J Phys Chem 98 887-893 Barvian MR, Greenberg MM (1992) Independent generation of the major adduct of hydroxyl radical and thymidine. Examination of intramolecular hydrogen atom transfer in competition with thiol trapping.Tetrahedron Lett 33 6057-6060... 

The intramolecular Heck reaction is a powerful method for the synthesis of constrained tertiary and quaternary carbon centers and has been applied as a key step in the synthesis of a number of pyridine alkaloids. Mann et al. have accessed the bicyclononane core structure of huperzine A 150 in moderate yield by intramolecular Heck reaction of bromopyridine 151 (Equation 117). Another notable application of this methodology is the intramolecular a-arylation of the amide enolate generated from 152 to give the carbon skeleton of cytosine <20040BC1825> (Equation 118). 

O.V. Shishkin et al., Intramolecular flexibility of DNA bases in adenine-thymine and guanine-cytosine Watson-Crick base pairs. J. Mol. Struct. 477, 15-21 (1999)... 

The intramolecular photodimerization and [2 + 2]-photocycloaddition in DNA involves thymine or cytosine as the chromophore. This chemistry has been intensively investigated with regards to DNA damage and repair [131]. Despite the fact that the area is of continuous interest [132], the synthetic applications are limited and are not covered here in detail. However, some preparative aspects of 4-pyrimidinone photocycloaddition chemistry will be addressed. Aitken et al. have prepared a plethora of constrained cyclobutane P-amino acids by intra- or intermolecular [2 + 2]-photocycloaddition to uracil and its derivatives [133, 134]. In a chiral adaptation of this method, the uracil-derived enone 140 was employed to prepare the diastereomeric cyclobutanes 141 in very good yield (Scheme 6.49). The compounds are easily separated and were - despite the relatively low auxiliary-induced diastereoselectivity - well suited to prepare the as-2-aminocyclobutanecarboxylic acids 142 in enantiomerically pure form. Enantioselective access to the corresponding trans-products was feasible by epimerization in a-position to the carboxyl group [135],... 

In 1985, Lyamichev et al. [15] called H-DNA to the intramolecular triplex of sequence PyPuPy in order to indicate the high H+ concentration of the media where this triplex exists. This requires protonation of one cytosine in each base-triplet and the two pyrimidine strands must run antiparallel. These form has undergone much research recently [16, 17], as it is very important to understand what is the role of triplex DNA in the nucleic acid characteristics and biotechnological applications may be of great relevance. 

The chloride ion is two-coordinated only in 1-methyl N-4-hydroxy cytosine hydrochloride [MHCYTC] (Fig. 15.18), and there is an intramolecular... 

In 5-aminouridine [AMURID], the weak three-center bond from 0(3 )H includes an intramolecular component ( ) to 0(20 and a rare example of an NH2 acceptor (Fig. 17.19). This group, however, is not conjugated as, for example, the amino group in adenine, guanine, and cytosine, but only in conjugation with the C(5)=C(6) double bond. We assume that it is still pyramidal with the lone electron pair located on the N atom, and therefore serves as hydrogen-bond acceptor. 

The hydrogen-bond structure of cytidinium nitrate [CYTIDN] (Fig. 17.33) contains the unusual bifurcated/three-center bond configuration, with strong bonds to the nitro oxygens (2.01 A and 1.94 A) and weak bonds (2.74 A and 2.58 A) to the hydroxyl oxygen 0(3 ). There is evidence of a three-center intramolecular bond ( ) with C(6)-H as donor and 0(4 ),0(5 ) as acceptors, similar to that observed in 0(2 )-methylcytidine (Fig. 17.36), and there is another three-center bond with the intramolecular 0(2 ) - H 0(3 ) as minor component ( ). The cytosine moiety is protonated at N(3). 

Intramolecular photocycloaddition occurs with thymine derivatives and related compounds. Thus, the bis thymine dimer (116) is formed on irradiation at 254 nm of (117). Zinc complexes of 1,4,7,10-tetraazacyclododecane inhibit the intramolecular photodimerisation of the thymidilyl thymidine (118) and the same complexes are active in cleaving cyclobutane systems (119). Conventional (2+2)-cycloaddition does not occur on irradiation of (120) but instead the main product is the cytosine hydrate accompanied by the (6-4)-photoproduct (121). Dimerisation is reported to occur on irradiation in an acidic medium. 

For pyrimidine nucleosides, the ease of anhydro-ring formation by intramolecular displacement is in the order 2,2 > 2,3 > 2,5. An-hydrocytidine derivatives are formed more readily than the corresponding anhydrouridines, and N4-acylation further enhances the nucleophilicity of the cytosine residue.419 N-Acyl-2,2 -anhydro-1 -/3-D-arabinofiiranosylcytosines are also more susceptible to hydrolysis at pH 7 than either 2,2 -anhydrouridine or 2,2 -anhydrocytidine. The product isolated after p-toluenesulfonylation of a mixture containing N-acetyl-3 -5 -di-0-acetylcytidine (146) was N-acetyl-l-(3,5-di-0-acetyl-/3-D-arabinofuranosyl)cytosine (149). The 2 -O-p-tolylsulfonyl intermediate (147) presumably cyclizes, to give the 2,2 -anhydride (148), which is rapidly hydrolyzed419 to 149. 

The intramolecular cyclocondensation of 1-(2-hydroxylaminoethyl) cytosine (90) gave pyrim-ido[2,l-c][l,2,4]oxadiazines (91) and (92) (Scheme 8) <71JCS(C)867>. The attempted esterification of aminooxy acetic acid intermediate (94) led by ring closure to (18) (Scheme 9) <70H(22)1879>. Some of the biologically active pyrimido[2,3-Z ][l,3,5]thiadiazines (9 were obtained from pyrimido-2-thiones (96) and A -aryl-AT-chloromethylcarbamoylchlorides (95) (Equation (18)) <83FRP2512450). 

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