2 -Pyrimidinones cytosines

Chemical Name 4-amino-1(3-D-arabinofuranosyl-2(1H)-pyrimidinone hydrochloride Common Name (3-cytosine arabinoside Structural Formula ... 

Kistler KA, Matsika S (2007) Cytosine in context a theoretical study of substituent effects on the excitation energies of 2-pyrimidinone derivatives. J Phys Chem A 111 8708-8716... 

Direct 5-fluorination can be effected on activated pyrimidines for example, F2 in HOAc or anhydrous HF have been used for the preparation of 5-fluoro-2(lH)-pyrimidinones (77CCC2694), and for 5,5-difluorination of 6-O-cyclouridines (83TL1055). Uracil and cytosine are 5-fluorinated by the same procedure (80TL4605,82CPB887). 

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],... 

The pyrimidine nucleobases have the highest quantum yields for photoreactivity, with thymine uracil > cytosine. The purine nucleobases have much lower quantum yields for photochemistry, but can be quite reactive in the presence of oxygen. As can be seen from Figure 9-3, thymine forms primarily cyclobutyl photodimers (ToT) via a [2ir + 2tt cycloaddition, with the cis-syn photodimer most prevalent in DNA. This is the lesion which is found most often in DNA and has been directly-linked to the suntan response in humans [65]. A [2Tr + 2Tr] cycloaddition reaction between the double bond in thymine and the carbonyl or the imino of an adjacent pyrimidine nucleobase can eventually yield the pyrimidine pyrimidinone [6 1]-photoproduct via spontaneous rearrangement of the initially formed oxetane or azetidine. This photoproduct has a much lower quantum yield than the photodimer in both dinucleoside monophosphates and in DNA. Finally, thymine can also form the photohydrate via photocatalytic addition of water across the C5 = C6 bond. 

The Isolation Technique Chromatography. Two alternatives are possible either to isolate the primary Hilbert-Johnson intermediates, i.e., l-peracylglycosyl-4-alkoxy-2(lH)-pyrimidinones, or to treat them with alcoholic hydrogen chloride or alcoholic ammonia and separate the corresponding A-l-glycosyl derivatives of uracil or cytosine. The latter alternative has been used by the earlier authors more frequently because of the higher crystallization ability of... 

Figure 4 Catalytic activation of cytosine for C5-methylation by nucleophilic addition of a thiolate at the C6 position, (a) The chemical mechanism of enzymatic DNA cytosine-S methylation. Mechanism-based inhibition of DMA MTases by cytidine analogs 5-fluoro-2 -deoxycytidine (b), 5-aza-2 -deoxy-cytidine (c), and 2-pyrimidinone-l-p-D-(2 -deoxyriboside) (d).

By far the most important naturally occurring diazines are the pyrimidinones uracil, thymine and cytosine, which, as the nucleosides uridine, thymidine and cytidine, are components of the nucleic acids, and as a consequence, a great deal of synthetic chemistry has been directed towards these types of compound in the medicinal context (33.6.3 and 33.7). (In this chapter, the designations 4-pyrimidinone and pyrimidin-... 

Two ligand-containing nucleosides that have the same cis-diimine metalbinding site as bpy have been synthesized and used in the synthesis of ligand-modified DNA duplexes (112,113). 4-(2 -Pyridyl)-pyrimidinone (Pyr ) (Entry 7, Table V) and 6-(2 -pyridyl)-purine (Pur ) (Entry 8, Table V) are formally obtained by substimtion of the 4-amino group of cytosine and of the 6-amino group of adenine with Py, respectively. Incorporation of a pair of Pyr or Pui ... 

Robins and Naik have reported that the reaction of cytosine (4-amino-2-(l//)-pyrimidinone) 218 with CF3OF in CCI3F followed by treatment with triethylamine in 50% aqueous methanol gives 217 in 85% yield (Scheme 12.49). 

Dimethoxypyrimidine allowed to react with acetyl diloride 1-acetyl-4-methoxy-2-pyrimidinone (Y 90-95%) heated 8 hrs. with 10 parts aq. or ale. NH3 at 100-120" in a sealed tube cytosine (Y 71%). F. e. s. H. Ballweg, Tetrah. Let. 1968, 2171. 

Amino-l-(2-amino-2-deoxy-l -D-arabino-fwanosyl)-2(lH) -pyrimidinone, 9 Cl. l-(2-Amino-2-deoxy-l -D-arabinofurano-syl) cytosine [67013-99-4]... 

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