3- 2- pyrimidon-4-ones formation

Extension of this work by studying the reaction of 3-methyl-5-nitro-pyrimidin-4(3//)-one with -X-arylketones in the presence of ammonium acetate surprisingly revealed the formation of a mixture of 4-arylpyrimidines and 6-arylpyridin-2(l//)-ones (00JCS(P1)27). The ratio between pyridine and pyrimidine formation is dependent on the substituent X. With electron-donating substituents the formation of the pyridin-2(l//)-ones is favored, with electron-attracting substituents the formation of the pyrimidine derivatives (Scheme 21) In the formation of the 6-arylpyridin-2(l//)-ones the C-4- C-5-C-6 part of the pyrimidone-4 is the building block in the construction of the pyridine ring. Therefore, the pyrimidone can be considered as an activated o -nitroformylacetic acid (Scheme 21). 

One such compound, bropirimine (112), is described as an agent which has both antineo-plastic and antiviral activity. The first step in the preparation involves formation of the dianion 108 from the half ester of malonic acid by treatment with butyllithium. Acylation of the anion with benzoyl chloride proceeds at the more nucleophilic carbon anion to give 109. This tricarbonyl compound decarboxylates on acidification to give the beta ketoester 110. Condensation with guanidine leads to the pyrimidone 111. Bromination with N-bromosuccinimide gives bropirimine (112) [24]. 

In an aqueous buffered medium, over the pH range 1-12, pyrimidone-2 exhibits a single one-electron wave. Preparative electrolysis, at a potential corresponding to the initial limiting current, led to formation of an insoluble product, isolated as a white amorphous powder, and shown by various physico-chemical criteria to correspond to a dimer consisting of two molecules of reduced pyrimidone-2. This was further confirmed by H NMR spectroscopy, which also established the structure of the product as 6,6 (or 4,4 )-bis-(3,6(4)-dihydropyrimidone-2), shown in Scheme 2, below. The structure of the dimer reduction product, and its solid state conformation, were subsequently further established by X-ray diffraction (see Sect. III.3.). 

In aqueous 0.1 M (CH3)4NBr, pyrimidone-2 was found to exhibit two reduction waves of equal height, with E1/2 values of —0.75 V and —1.55 V for waves I and II, respectively 1,2). (Fig. 1) Preparative electrolysis under these conditions at the potential of wave I resulted in formation of the same dimer reduction product as in aqueous buffered medium. By contrast, electrolysis on wave II led to formation of two products, one of which was identical with that formed on wave I. The other, readily soluble in aqueous medium, was identified as 3,6-dihydropyrimidone-2, identical with that synthesized chemically and described earlier by Skaric75). 

In acid medium (pH 4.5) electrochemical reduction led to formation of two products. One of these was characterized as the 6,6 -dimer of the riboside of pyrimidone-2. It was photochemically converted to the riboside of pyrimidone-2. The second, on the basis of its chromatographic behaviour, UV spectrum, and reaction with the Fink reagent, was identified as the riboside of 3,6-dihydropyrimidone-2. The mechanism of electrochemical reduction of cytidine in acid medium is consequently analogous to that for 1-methylcytosine. The products of reduction of cytidine at pH 7 were shown chromatographically to contain 5,6-dihydrocytidine 1 84). A comparison of the electrochemical and catalytic reduction products under analogous conditions at pH 7 demonstrated that both led to the same products, one of them 5,6-dihydrocytidine 84). 

In view of the earlier demonstration that pyrimidone-2 undergoes one-electron reduction, with formation of a dimer identified as 6,6 -6ij-3,6-dihydropyrimidine-2, which is suceptible to quantitative photodissociation to the parent pyrimidone-2, and bearing in mind that 2-oxopurine may be considered a formal analogue of a 5,6-disubstitut-ed pyrimidone-2, it appeared of interest to examine whether an analogous reaction sequence occurs with 2-oxopurine. 

Cytosine (257) loses ammonia in a two-electron reduction298 with the formation of 2-pyrimidone (258), which, as other pyrimidones,200 is reduced in a one-electron reaction with dimerization. 

Another major form of base damage generated in DNA by UV light is one in which the C6 position of a 5 pyrimidine is covalently linked to the C4 position of the 3 adjacent pyrimidine (Fig. 6). These lesions [which are readily detected by their lability in alkaline conditions at 80-100° C (43)], are called pyrimidine-pyrimidone [6-4] adducts, or simply [6-4] photoproducts ([6-4]PP). The pyrimidine planes in ([6-4]PP) are almost perpendicular. Hence, they result in prominent distortions of the double-helical structure of DNA. ([6-4]PP) can involve adjacent TC, CC, or (less often) TT sequences. Their formation at CT sequences is infrequent. Cytosine methylation at the C5 position inhibits the formation of [6-4]PP (44). The yield of [6-4]PP is proportional to the incident UV fluence in the range 100-500 J/m and continues to increase after exposure to several thousand J/m (1). In UV-C irradiated DNA, the ratio of CPD [6-4]PP is 3 1 (1). 

Certain ylides react with arylcyclopropenones via 1,4-addition to give a-pyrone and its heterocyclic derivatives the formation of the l,3-oxazin-6-one 336 from reaction of the pyridine-iV-imine 335 with 14 is representative. Pyrimidones, pyridines and related... 

In the search for inhibitors of cell adhesion molecule expression in human endothelial cells, thieno[23-d]pyrimidin-4-one 36 was first subjected to a Krapcho dccarboethoxylation. The resultant pyrimidone was then converted to 4-chlorothieno[23-leaving group, new C-S and C-N bond formations were easily achieved by SnAf displacements to produce 38 <01JMC988>. Yields were not given for all compounds... 

The selective hydrolysis of 2,4-diaminopyrimidincs 53 to 4-aminopyrimid-2-ones 54 under acidic conditions was also reported. Treatment of 53 with 6M HCl led to the formation of pyrimidone 54, which contrasts with the regioslectivity usually observed with 2,4-diaminopyrimidines <01JOC192>. 

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