6-substituted purines

Potential, chemotherapeutic activity of this class of compounds stimulated the synthesis313,337,352 of a series of benzimidazole-, pyrimidine-, and purine-substituted nucleosides of D-glucuronic acid derivatives, using, as the starting sugar-component, bromide 1 and methyl (2,3,4-tri-0-acetyl-D-glucopyranosylamine)uronate, respectively. 

C N.m.r. has been used to distinguish between 7- and 9-purine substitution in ribofuranosyl nucleosides useful signals are those of C-1 which differ for the two types and those of the carbon atoms of the purine moiety which are characteristic for the two types of substitution. The anomeric configuration of mycosamine in the polyene antifungal antibiotics lucensomycin and nystatin has been determined by C n.m.r. the former contains an a-mycosaminyl residue while the latter is a j8-mycosaminide. ... 

Purines, substituted (direct injection, EEE, SPE) Racemethorphan, racemorphan (optical isomers) Theophylline metabohtes (SPE)... 

In many cases, the chemical nature of ring substituents had markedly different effects with each enzyme. Figure 6 illustrates this point by comparing the rates of oxidation by xanthine oxidase and aldehyde oxidase of some purines substituted with different chemical groups at the 6-position. 

Firefly lucifenn is an example of an azole that contains a benzene ring fused to the five membered ring Such structures are fairly common Another example is benzimidazole present as a structural unit m vitamin B12 Some compounds related to benzimidazole include purine and its ammo substituted derivative adenine one of the so called het erocychc bases found m DNA and RNA (Chapter 28)... 

Both pynmidme and purine are planar You will see how important this flat shape is when we consider the structure of nucleic acids In terms of their chemistry pyrimidine and purine resemble pyndme They are weak bases and relatively unreactive toward elec trophilic aromatic substitution... 

These relationships are general Hydroxyl substituted purines and pyrimidines exist in their keto forms ammo substituted ones retain structures with an ammo group on the ring The pyrimidine and punne bases m DNA and RNA listed m Table 28 1 follow this general rule Beginning m Section 28 7 we 11 see how critical it is that we know the cor rect tautomeric forms of the nucleic acid bases... 

The structure of guanine illustrates an important feature of substituted pyrimidines and purines Oxygen substitution on the ring favors the keto form rather than the enol Ammo substitution does not... 

Thiazolo[5,4-d]pyrimidine, 2,5,7-trichloro-nucleopfulic substitution, 6, 686 Thiazolo[3,2-a]pyrimidine-5,7-diones IR spectra, 6, 672 Thiazolopyrimidines synthesis, 5, 572, 574, 578 Thiazolopyrimidines, amino-purine synthesis from, 5, 591 Thi azolo[3,2-ajpyrimidines synthesis... 

The names of 2-aza analogs are derived by formal substitution of the methine group in the 2-position of the purine skeleton by a nitrogen atom (140). Since this position is substituted in some purine bases, only the aza analogs of adenine or hypoxanthine are amenable to such formal derivation. 

The 8-aza analogs are formally derived by substitution of the methine group in position 8 of the purine ring. The names thus derived preserve the numbering of the purine ring (146), and are frequently used in papers of biochemical character, but in chemical papers only along with systematic names. 

More interesting are the substitution reactions on the triazole ring where a characteristically different course can be expected from that of analogous reactions in the purine series. These reactions were studied in more detail only in connection with the preparation of the glycosyl derivatives, and the experimental material does not permit the drawing of general conclusions. 

It would not be too far fetched to state that life on this planet is totally dependent on two compounds based on the purine nucleus. Two of the bases crucial to the function of DNA and flNA—guanine and adenine—are in fact substituted purines. It is thus paradoxical that the lead for the development of medicinal agents based on this nucleus actually came from observations of the biologic activity of plant alkaloids containing that heterocyclic system, rather than from basic biochemistry. 

Substitution of somewhat more complex side chains on the imidazole nitrogen of the purines leads to CNS stimulant drugs that have also been used as vasodilators and antispasmodic agents. Thus, alkylation of theophyline (2) with ethyl bromoacetate followed by saponification of the product gives acephylline (9). Alkylation with l-bromo-2-chloroethane gives the 2-chloroethyl derivative (10). Reaction of that intermediate with amphetamine yields fenethylline (11). ... 

Substitution of more complex acids for formic acid in the last step of the purine synthesis will afford intermediates substituted on the imidazole carbon atom. Thus, condensation of diaminouracyl, 12, with phenylacetic acid gives the benzylated... 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

The sugar component in RNA is ribose, and the sugar in DNA is 2 -deoxy-ribose. (The prefix 2 -deoxv indicates that oxygen is missing from the 2 position of ribose.) DNA contains four different amine bases, two substituted purines (adenine and guanine) and two substituted pyrimidines (cytosine and thymine). Adenine, guanine, and cytosine also occur in RNA, but thymine is replaced in RNA by a closely related pyrimidine base called uracil. 

With hydrobromic acid and potassium bromate 7-methylxanthine (159 X = H) gave the 2-bromo derivative (159 X = Br) in 83% yield (84CHE924). Conversion of a variety of 2-substituted-6-trifluoromethyl-purines into the anions, followed by treatment with NBS in hot dimethyl-formamide, gave 20-60% yields of 2-bromo derivatives (90JHC1505). 

Thiourea and allylthiourea (20), D-xylulose (22), sodium diethyldithiocarbamate, L-methionine, and -propyl-di- -propylthiol-carbamate (163), 12 6-(substituted) purines (166), and two coumarin derivatives (164) have been found to promote Striga seed germination. None of these materials, however, appear to be constituents of the natural stimulant preparations. 

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. 

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