Purine ring system

FIGURE 11.2 (a) The pyrimidine ring system by convention, atoms are numbered as indicated, (b) The purine ring system, atoms numbered as shown. 

The aromaticity of the pyrimidine and purine ring systems and the electron-rich nature of their —OH and —NHg substituents endow them with the capacity to undergo keto-enol tautomeric shifts. That is, pyrimidines and purines exist as tautomeric pairs, as shown in Figure 11.6 for uracil. The keto tautomer is called a lactam, whereas the enol form is a lactim. The lactam form vastly predominates at neutral pH. In other words, pA) values for ring nitrogen atoms 1 and 3 in uracil are greater than 8 (the pAl, value for N-3 is 9.5) (Table 11.1). 

Anti-gout Drugs. Figure 1 Xanthine oxidase-catalyzed reactions. Xanthine oxidase converts hypoxanthine to xanthine and xanthine to uric acid, respectively. Hypoxanthine and xanthine are more soluble than uric acid. Xanthine oxidase also converts the uricostatic drug allopurinol to alloxanthine. Allopurinol and hypoxanthine are isomers that differ from each other in the substitution of positions 7 and 8 of the purine ring system. Although allopurinol is converted to alloxanthine by xanthine oxidase, allopurinol is also a xanthine oxidase inhibitor. Specifically, at low concentrations, allopurinol acts as a competitive inhibitor, and at high concentrations it acts as a noncompetitive inhibitor. Alloxanthine is a noncompetitive xanthine oxidase inhibitor. XOD xanthine oxidase. 

The overall strategy is to build the carbon-nitrogen skeleton of a purine ring system in a 12-step process directly on the sugar-phosphate starting material, a. The first step creates the multi-purpose intermediate 5 -phosphorihosyl-l-... 

The purine ring system is built up step-by-step beginning with 5-phosphoribosylamine. The amino acids glutamine, glycine, and aspartate... 

A structure determination of CdL(H20)5 3H20 (L = guanosine-5 -phosphate) reveals a cadmium ion octahedrally coordinated by live water molecules and the N-7 of the purine ring system (Cd—N = 2.37 A Cd—O = 2.24-2.34 A).568 Similarly, a structure determination of CdL2(H20)4 (L = 8-azahypoxanthinato) reveals octahedral cadmium bonded to N-7 of the purine anions and to four water molecules.569 Theophylline (83) is frequently used as a substitute for guanine (84) in model systems, and the complexes [CdI (RNH2)2(H20)2] (L = 83) have been described.570... 

The structure of saxitoxin (Figure 6.136) contains a reduced purine ring system, but it is not biosynthetically related to the purine alkaloids... 

Caffeine (1.10), found in coffee (Coffea arabica), was introduced to Europe through Constantinople (modem Istanbul) in the 1500s (Figure 1.5). The stimulant effects of coffee were widely acknowledged, but coffee was recognized as a useful diuretic. Caffeine was first synthesized by Emil Fischer in 1882. Two related compounds, theobromine (1.11) and theophylline (1.12), found in cacao seeds (Theobroma cacao) and tea (Camellia sinensi), respectively, are more potent diuretics than caffeine.1 All three compounds are based on the purine ring system (1.13). 

The purine ring system undergoes substitution by both nucleophilic and electrophilic reagents, although with the latter the substituted atom is usually nitrogen rather than carbon. Attempts, made by various schools of theoretical chemistry, to predict the relative order... 

The caffeine structure is shown below. It is classed as an alkaloid, meaning that with the nitrogen present, the molecule has base characteristics (alkali-like). In addition, the molecule has the purine ring system, a framework which plays an important role in living systems. 

With very few exceptions, by far the most important synthetic routes to the purine ring system remain the Traube synthesis from pyrimidines and the synthesis achieved by cyclization of an appropriate aminoimidazole. One of the more active areas of synthesis since the mid-1980s has been the acyclonucleosides, i.e. purines, especially guanine, with a 9-substituent which possesses some of... 

Figure 10.5 Origin of each atom of the purine ring system.

The purine bases are formed from the parent compound purine, which in turn is formed by the fusion of a pyrimidine and an imidazole ring. The parent purine structure and systematic numbering are shown in Fig. 2. Like the pyrimidine class of compounds, purine ring systems are it electron deficient however, unlike pyrimidines, there is no position in the ring... 

The purine ring system is undoubtedly among the most ubiquitous of all the heterocyclic compounds. This arises not only from the universal occurrence of adenine and guanine in DNA and RNA and of additional modified derivatives in the various tRNAs but also from the subsidiary uses of the ring system in very many biochemical systems Indeed across the whole spectrum of biochemical reactions in living systems there is hardly a reaction sequence which does not involve in some way a purine derivative such as the adenosine or guanosine mono-, di- and tri-phosphates, associated cyclic phosphates and nucleotide coenzymes. 

Electron-releasing groups are required in the purine ring system before nitration can occur. In this way 8-nitro-caffeine (149), -theophylline (150), and -theobromine (151) have been prepared by nitration of the appropriate purine with nitric acid, neat or in acetic acid (71HC(24-2)i, p. 402). Similarly, 9-methylxanthine, but not xanthine, undergoes nitration to 9-methyl-8-nitroxanthine (60JA3773). 

There are only a few recorded reactions of N-alkylpurines which result in preservation of the purine ring system, since ring opening generally occurs and pyrimidines or imidazoles are produced. Halogenation may, however, lead to iV-chloromethyl derivatives as with 2,7-dimethylpurine which can be chlorinated to form 7-chloromethyl-2-methylpurine. Details of reaction products derived from some alkylpurines are collected in Table 25. 

Derivatives of the five imidazothiadiazines pictured in the introduction are known. The most research has been carried out on 4,5-fused systems, where the impetus, at least partially, has been their resemblance to the purine ring system. 

The purine ring system represents a fusion of the two aromatic heterocycles pyrimidine and imidazole. As a logical consequence, appropriately substituted pyrimidines or imidazoles have been used as precursors followed by a cyclization reaction. The purine heterocycle can also be formed from simple acyclic precursors. The most widely used method to synthesize purine is the addition of an imidazole ring to a functionalized pyrimidine moiety (Traube synthesis). The alternative route for the formation of the purine system by the annulation of the pyrimidine ring to a substituted imidazole relates back to a method of Sarasin and Wegmann, and these synthetic protocols principally follow the biosynthetic pathway of purine synthesis. 

Substituted 4(5)-aminoimidazole-5(4)-carbonitriles are versatile starting materials for the synthesis of purine ring systems. The combination of an electrophilie cyano group proximate to a nucleophilic amino function results in a one-step addition-cyclization reaction of electrophiles to give purine analogs. Triethyl orthoformate is widely used for the preparation of adenine and adenine derivatives without a substituent at C2. 

The Purine Ring System Is Assembled on Ribose Phosphate... 

The bases found in DNA are adenine and guanine which contain the purine ring system, and cytosine, thymine, and S-methylcytosine, which contain the pyrimidine ring system. RNA contains adenine, guanine, cytosine, and uracil. (See Fig. 37.6.)... 

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