Purines derivatives

6-dimethylbenzimidazole residue is derived from riboflavin (D 10.4.3). The l-amino-2-propanol unit is formed from L-threonine by decarboxylation  

Cobalamins are vitamins for higher animals and humans (vitamins E 2.1). They are transformed to two types of coenzymes  

Akhtar, M., Jordan, P. M. Porphyrin, chlorophyll and corrin biosynthesis. In Comprehensive Organic Chemistry, Vol. 5, Biological Compounds (E. Haslam, ed.), pp. 1121-1166. Pergamon Press, Oxford 1979 

Friedrich, W. Vitamin B12 and verwandte Corrinoide. In Fermente - Hormone - Vitamine (R. Ammon, W, Dirscherl, eds.), Vol. III/2. Thieme, Stuttgart 1975 Schrauzer, G. N. Mechanisms of corrin-dependent enzymatic reactions. Prog. Chem. Org. Nat. Prod. 3i, 583-628 (1974) 

Purines are heterocyclic compounds with the following basic skeleton  

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The C-S bond in purine derivatives undergoes cleavage under mild conditions by nucleophilic agents such as benzylmercaptan or glutathione in dimethylformamide with a phosphate buffer of pH 6.5 (277). The salt (110) of dithiazolylsulfide heated at 190 C yields the A-4-thiazo-line-2-thione (112) and 2-chlorothiazole (111) (Scheme 56) (278-280). 

Astcracantha longifolia Ness (Aeanthacese). This plant, formerly named Hygrophila spinosa, contains an alkaloid, C10H12O3N4, m.p. 216-7°, which forms an oxalate, m.p. 221-2°, and a sulphate, m.p. 210-1°, and may be a purine derivative (Basu and Lai, Qtiart. J. Pharmacol., 1947, 20, 38). 

Adenine (6-amino purine) and guanine (2-amino-6-oxy purine), the two common purines, are found in both DNA and RNA (Figure 11.4). Other naturally occurring purine derivatives include hypoxanthlne, xanthine, and uric acid (Figure 11.5). Flypoxanthine and xanthine are found only rarely as constituents of nucleic acids. Uric acid, the most oxidized state for a purine derivative, is never found in nucleic acids. 

FIGURE 11.5 Other naturally occurring purine derivatives—hypoxanthine, xanthine, and uric acid. 

As is well-known, nucleic acids consist of a polymeric chain of monotonously reiterating molecules of phosphoric acid and a sugar. In ribonucleic acid, the sugar component is represented by n-ribose, in deoxyribonucleic acid by D-2-deoxyribose. To this chain pyrimidine and purine derivatives are bound at the sugar moieties, these derivatives being conventionally, even if inaccurately, termed as pyrimidine and purine bases. The bases in question are uracil (in ribonucleic acids) or thymine (in deoxyribonucleic acids), cytosine, adenine, guanine, in some cases 5-methylcytosine and 5-hydroxymethylcyto-sine. In addition to these, a number of the so-called odd bases occurring in small amounts in some ribonucleic acid fractions have been isolated. 

For this reason dual terminology is in use for the aza analogs. The first, derived from the principal pyrimidine and purine derivatives by means of the prefix aza- is used almost exclusively in biochemical papers in organic chemistry is it used together with the systematic names) wherever it is desired to compare the properties of the natural bases and of their aza analogs. The systematic terminology is naturally used in the older literature where no biochemical aspects of the compounds were considered, and in some newer work of strictly chemical nature. Since the numbering of the substituents is in some cases different for the different systems, we shall discuss this in more detail later. ... 

According to the systematic nomenclature these substances were first named l-f-triazolo[d] pyrimidines in compliance with the general principles of the Ring Index/ More recent papers and Chemical Abstracts indexes use the term i -triazolo[4,5-d]pyrimidine (147) in accord with the lUPAC nomenclature. The numbering of substituents when using the last-mentioned name is different from that of the 8-aza analogs. For the formulas of oxygen and sulfur derivatives names derived from the lactim or thiolactim form are almost exclusively in use (in common with the purine derivatives). These derivatives are thus described as hydroxy and mercapto derivatives, respectively. The name 1,2,3,4,6-pentaazaindene is used only rarely for this system. 

The TJV spectra were measured for practically all the numerous derivatives. Beside the analytical application of these to demonstrate the position of the substituent no detailed interpretation was attempted, however. On the whole, they are similar to the spectra of analogous purine derivatives and also display a similar dependence on Despite the fact that the question of structure with regard to the lactim-lactam (or thiolactim-thiolactam) tautomerism has not been studied in detail, it can be assumed that oxygen and sulfur derivatives, at variance with the conventional way of writing the formulas, possess a lactam or thiolactam structure. This is in agreement with the views on the analogous purine derivatives. 

The preparation of purine derivatives substituted at the C-2 position via amine displacement of a halogen is known as a difficult reaction step requiring several days of reaction time. However, Al-Obeidi and coworkers have recently prepared 2,6,9-trisubstituted purines on soUd-phase by employing a synthetic route in which the critical step was performed with microwave irradiation (Fig. 37) [62]. PS resin-bound 2-iodosubstituted purine was treated with diethanolamine or propanolamine in NMP with microwave irradiation at 200 °C for 30 min. Trifluoroacetic acid-mediated cleavage resulted in the 2-amino substituted purines in 45-59% yields and 77-89% purities. 

The cyclization of o-substituted amides 206 was used for the preparation of a series of purine derivatives 207. In this case, the amine behaved as a nucleophile toward the amide function followed by ring closure to the imidazole ring (Scheme 75) [133]. 

Care must be exercised in the choice of acid employed in chloramine T — mineral acid reagent since the detection sensitivity and also the color of the fluorescences produced depend to a significant extent on the choice of acid. This is illustrated for the purine derivatives caffeine, theobromine and theophylline in Figure 1 and Table 1. 

Only theophylline yields an intensely fluorescent derivative under long-wavelength UV light when treated with chloramine T — sodium hydroxide reagent. The purine derivatives caffeine and theobromine investigated at the same time fluoresce very weakly or not at all. 

Fig. 1 Comparison of the detection sensitivity after derivatization of three purine derivatives with chloramine T - sulfuric acid (A) and chloramine T - hydrochloric acid (B). Measurement X. (. = 365 nm, A.(, = 440 nm (monochromatic filter M 440) 1 = theophylline, 2 = theobromine, 3 = caffeine.

Purine derivatives (e. g. xanthine) are oxidized by chloramine T in the presence of hydrochloric acid and form purple-red anunonium salts of purpuric acid (murexide) with ammonia. Whether the murexide reaction is also the cause of the fluorescence is open to question. 

Purine derivative yield pinkish-red chromatogram zones on an almost colorless background [1-3]. The chromatogram is then heated to ca. 100 °C again until the color development reaches maximum intensity (yellow to orange). On excitation with... 

The chromatograms are freed from mobile phase in a stream of warm air, immersed in the dipping solution for 2 s or homogeneously sprayed with the suitable spray solution and then dried in air or in a stream of cold air. Alternatively purine derivatives can be treated successively with the two spray solutions IIA and IIB (with 2 min air drying in between) [6, 7J. 

Note The dipping solution can also be used as spray solution. Since the chromatogram zones slowly fade in the air it is recommended that the chromatograms be covered with a glass plate for long-term storage. Color differentiation is possible with purine derivatives [6, 8]. Diprophylline is not colored [6]. 

The detection limits for purine derivatives are 120-400 ng and for antibiotics 50 ng substance per chromatogram zone [4]. 

The reagent can, for instance, be employed on silica gel, kieselguhr. Si 50000, cellulose and NH2 layers the reaction is appreciably less sensitive on RP 18, CN and Diol phases, neither is there any color differentiation of the purine derivatives [8J. Cellulose and polyamide layers are not suitable, since the whole layer background is colored dark brown [8]. 

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