Pyrimidine structures

Examination of the pyrazino[2,3-rf]pyrimidine structure of pteridines reveals two principal pathways for the synthesis of this ring system, namely fusion of a pyrazine ring to a pyrimidine derivative, and annelation of a pyrimidine ring to a suitably substituted pyrazine derivative (equation 76). Since pyrimidines are more easily accessible the former pathway is of major importance. Less important methods include degradations of more complex substances and ring transformations of structurally related bicyclic nitrogen heterocycles. 

A. Synthesis by Annulation of the 1,2,4-Triazole Ring ONTO A Pyrimidine Structure... 

Assignment of the l,2,4-triazolo[l,5-c]pyrimidine structures to the products obtained from the previously described cyclizations and not the alternative [4,3-c] structures has been rationalized and corroborated on the basis of (a) preference of cyclization at the more nucleophilic triazole ring N2 rather than at its less nucleophilic N4 (65JOC3601 88JMC1014), (b) inability of the obtained products to undergo acid- or base-catalyzed Dimroth rearrangement, a property characteristic of the thermodynamically less stable [4,3-c] isomers (91JMC281), (c) comparison with unequivocally prepared... 

In other words, a synthetic route to polypeptides which requires only HCN and water is presented preformed a-amino acids are not necessary. According to Matthews, the pyrolysis of cyanide polymers can give nitrogen-containing heterocycles with purine and pyrimidine structures in other words, the HCN world ... 

Some compounds having quite similar pyrazolo[4,3- pyrimidine structures have been claimed in the patent literature to be potent phosphodiesterase inhibitors. Some are claimed to act also upon female sexual dysfunctions. 

N2,N4,NkTripicrylmelamine (TPM) [Structure (2.31)] has been reported to be a moderately thermally stable explosive with performance a little better than that of TNT [75]. Subsequently, heterocyclic nitrogen atoms of TPM were systematically replaced [76, 77] with the C-nitro function to give nitro-substituted tris(picrylamino) derivatives of pyrimidine [Structure (2.32)], pyridine [Structure (2.33)] and benzene [Structure (2.34)] given in Figure 2.2. 

For the bicyclic product arising from the sodium ethoxide-catalyzed reaction of 2-aminopyridine and isonitrosocyanoacetate, Glushkov and Magidson30 considered both the 4-amino-3-nitroso-2-oxo-2H- and the 2-amino-3-nitroso-4-oxo-4//-pyrido[l,2-a] pyrimidine structures, preferring the former. This structure, however, can be questioned on the basis of the patent of Kummer et al.31... 

The structure of the reaction product of 2-aminopyridine and diethyl malonate, described by Chichibabin as 2,4-dioxo-3,4-dihydro-2//-pyrido-[l,2-<7]pyrimidine,96 was first questioned by Snyder and Robison253 on the basis of the high melting point and poor solubility of the compound. They suggested the tautomeric 2-hydroxy-4-oxo-4H-pyrido[l,2-a]pyrimidine structure. The problem was solved by Katritzky and Waring273 who compared the UV spectrum of the product with that of fixed tautomers and found that the product may best be described as anhydro- 2-hydroxy-4-oxo-4/f-pyrido[l,2- ]pyrimidinium)hydroxide (63). Because of the chemical behavior of these compounds, however, the contribution of other mesomeric forms to the structure has also been considered.122 Thus, PPP-SCF quantum chemical calculations suggest that 1,4-dipolar cycloadditions to the C-3 and C-9a atoms are to be expected.352 This type of reaction does in fact occur (see Section III,C,10). Katritzky and Waring273 estimated the ratio of the mesomeric betaine (63 R = H) and the 2-hydroxy-4-oxo tautomers to be about 20 1. 

The two nitrogens in the pyrimidine structure are also likely candidates for enzymatic oxygenation. Indeed, the antibacterial agent 2,4-diamino-5-(3,4,5-trimethoxybenzyl)... 

Naturally occurring pterin derivatives have existed in 3 oxidation states pterin (4 aromatic), dihydropterin (e.g., 5-8) and tetrahydropterin (9). In the present review, we do not refer to reduced pterin derivatives with reduced pyrimidine structures. The reduced pterin derivatives, dihydropterin and tetrahydropterin are readily oxidized to the corresponding aromatic form (4) under aerobic conditions. Based on the location to which hydrogen atoms are added, 4 kinds of dihydropterin have been defined 7,8-dihydropterin (5), quinonoid dihydropterin (6), 5,6-dihydropterin (7) and 5,8-dihydropterin (8). Of these, only 7,8-dihydropterin derivatives can be stored for long periods under non-aerobic conditions. Indeed, several 7,8-... 

By contrast, if a pyrimidine is to be made, Nature assembles a general pyrimidine structure first and adds it in one step to the PRPP molecule, again in an S>j2 reaction using a nitrogen nucleophile. This general nucleotide, orotidylic acid, can be converted into the other pyrimidine nucleotides by simple chemistrv. 

Alchornine (73) and alchornidine (74a or 74b) have been isolated by Hart et al. (126) from the bark and leaves of Alchornea javanensis (Bl.) Muell.-Arg. (Euphorbiaceae), a small tree of the New Guinea rain forest. From spectroscopic data and chemical evidence, the major alkaloid alchornine was shown to have the hexahydroimidazo[l,2-a]pyrimidine structure 73. Hydrolysis of a minor alkaloid, alchornidine, with ethanolic potassium hydroxide gave alchornine and 2,2-dimethylacrylic acid. But alchornidine is not simply an A-acyl derivative of alchornine, because mild hydrolysis with dilute acetic acid gives an isomer of 73. This isoalchornine can be shown to be 75, and it is readily converted to alchornine by reaction with alkali. This... 

Each nucleoside is constructed from two components—a deoxyribose sugar and a base. The sugar is the same in all four nucleosides and only the base is different. The four possible bases are two bicyclic purines (adenine and guanine), and two smaller pyrimidine structures (cytosine and thymine) (Fig. 6.2). 

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