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Eine Methode zur Abtrennung von Adenin und Guanosin aus Blutkonserven und Plasmafraktionen (nachCobn) nach Verwendung purinderivathaltiger ACD-Stabilisatoren wird beschrieben. Die hochste gefundene Konzentration je Gramm Humanalbumin oder γ-Globulin betrug fur Adenin 0,5 mg. Auf Grund von Wechselwirkungen mit Blutzellen ist Guanosin im Frischplasma nicht vorhanden; es konnte erst nach mindestens einwochiger Lagerung des Vollblutes im Plasma nachgewiesen werden. Die in Therapie-Produkten zu erwartenden Mengen an Adenin und Guanosin konnen nach den bisher bekannten pharmakologischen Untersuchungen als unbedenklich gelten.

Condensation products of amino acids and proteins with biologically active purines have been obtained to study their potential tumor inhibitory activity and as models for the preparation of conjugates with tumor specific antibodies. Among the new compounds are 2-glycinyl-6-methylmercaptopurine (5), 2-glycinyl-6-mercaptopurine (6), 2-glycinyl-6-chloropurine (16), 2-glycinyl-6-hydroxylaminopurine (18), 2-glycinylpurine (8) and 2-glycinyl-6-methylpurine (7). 9-Alkylpurines led to new purine derivatives, such as 6-chloro-9H-purine-9-acetic acid (22) and 6-hydroxylamino-9H-purine-9-acetylhydroxamic acid (23). These derivatives were coupled to bovine serum albumin (BSA) to yield conjugates. The amino acid-purines 6-cysteinyl (27) and 6-glutathionyl-S-purine 3-oxide (28) were obtained from 6-chloropurine 3-oxide (26). Other protein-purine 3-oxide conjugates were obtained with 6-mercaptopurine 3-oxide (29) and 6-bromomethylpurine 3-oxide (33).

Fusion of 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-β- d -glucopyranose, 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthalimido-β- d -glucopyranose, and 1,3,4,6-tetra-O-acetyl-2-benzamido-2-deoxy-β- d -glucopyranose with 2,6-dichloropurine, theophylline, and 6-benzylaminopurine in activating agents afforded the corresponding aminonucleosides in good yields. The simultaneous formation of a positional isomer was confirmed in three examples in the reactions with 2,6-dichloropurine and 6-benzylaminopurine. On the basis of these results, the potential effect of 2-acylamido functional groups on the reaction is discussed.

Adenosine and its related compounds reacted with hydroxylamine-O-esters to give the corresponding 1-amino derivatives. 1-Amino-adenines were rearranged in the presence of alkali to afford 5(4) - amino - 4(5) - (1,2,4 - triazol - 3 - yl) - imidazole. 1-Amino derivatives reacted with ethyl orthoformate to give 7H - s - triazolo[3,2 - i] - purine derivatives and with H 2 S to give 1 - amino - 6 - mercaptopurines. All the 1-amino derivatives were readily deaminated to the parental adenines by treatment with NaNO 2 .

Xanthine oxidase (EC 1.2.3.2) has been shown to reduce the N-oxide function of several purine N-oxide derivatives. The reaction requires anaerobic conditions and electron donors such as xanthine, hypoxanthine, sodium dithionite, or DPNH. With no other electron donor present, the purine N-oxide can also serve as the electron donor if it has an oxidizable carbon atom. With sodium dithionite as the electron donor, a spectrometric procedure has been devised which permits measurement of the enzymatic reduction of N-oxides or other compounds by monitoring the disappearance of the dithionite absorption. The enzymatic synthesis of 8-hydroxyguanine 3-oxide is described.

Proton chemical shifts are examined in a series of twelve purine and three 5-azapurine derivatives. The assignment of N-H signals in the xanthine and thioxanthine series, as well as the effects of moisture, concentration and temperature on the N-H and C-H nmr spectral characteristics are discussed.

1. 1. The reactivity of pteridine and all its hydroxy derivatives towards mammalian xanthine oxidase from cow's milk has been studied. In this series, 12 out of 15 potential substrates are attacked. The three resistant derivatives are 6-Pt, 2,6-Pt and 2,4,7-Pt. 2. 2. Two series of substrates can be defined: (a) Pteridines with a free 6-position are all converted finally into 2,4,7-Pt; (b) Pteridines wiht a preformed 6-hydroxyl group are either resistant to enzymic attack or are oxidized finally to 2,4,6,7-Pt. In both series, only C-2, C-4 and C-7 are susceptible to oxidation. 3. 3. The pathway of oxidation differs in one case from that of the corersponding purine derivative. 4-Pt is attacked first at C-7, whereas its analogon, hyppoxanthine, is oxidized first at C-2. 4. 4. In the pteridine series, several examples have been found for simulations reaction along two pathways: Pteridine itself is attacked at C-2 and C-4. 2-Pt is oxidized to a mixture of 2,4- and 2,7-Pt. For 4,6-Pt the formation of 4,6,7-Pt as intermediate—in addition to the major product 2,4,6-Pt—has not been established beyond doubt. 5. 5. These results are discussed on the basis of the fundamental structural difference between pteridines and purines, viz. the replacement of the NH-group in the imidazol ring by a CN-double bond.

1. 1. Splitting, tension and relaxing effect of nucleosidetriphosphate (NTP) are activated by magnesium ions. 2. 2. For each NTP the Mg ++ requirement is the same for splitting and tension. The Mg ++ requirement for the relaxing effect is much less. 3. 3. The amount of Mg ++ required for hydrolysis and tension increases from ATP to GTP in the order With more complete Mg ++ activation the development of tension decreases in the same order This also applies for the splitting (with the exception of acetyl-ATP). 4. 4. The extent of tension development always depends on the extent of the rate of splitting. It is thus immaterial whether or not the rates of splitiing are of varying magnitude since the splitting of the same NTP by Mg ++ is activated to a varying extent. Only acetyl-ATP develops with equal splitting less tension than the other NTP's. 5. 5. The Mg ++ requirement for the relaxing effect increases in the order: When the Mg ++ activation is maximal the relaxing effect decreases in the same order. 6. 6. The diversity of the NTP succession for tension and splitting on the one hand and for the relaxing effect on the other shows that considerable tension and splitting is produced when the NTP concerned contains an NH 2 group in the 6-positio — whether in the purine or the pyrimidine ring. The relaxing effect is by comparison greater with purine derivatives than with pyrimidine derivatives, independent of the presence of the NH 2 group in the 6-position in the ring system. 7. 7. The relaxing effect and tension development, in contrast to splitting, are not activated by Ca ++ ions. 8. 8. The “relaxing factor” ( Marsh ) works only in the presence of ATP in concentrations > 2 · 10 −3 M or of acetyl-ATP and CTP in concentrations −3 M . 9. 9. The “relaxing factor” does not, however, work in the presence of ITP, UTP and GTP in concentrations up to 10 −2 M . 10. 10. It is shown that the inter-action between actomyosin and NTP's does not depend on the fact that ATP is built up from the bound ATP of the actomyosin and the other NTP by means of nucleodiphosphokinase.

An examination of the site where the acidic catalysts might strongly interact in the fusion reaction of a purine derivative with a fully-acylated sugar led to the conclusion that a purine derivative was activated by the interaction with the catalysts, and, moreover, resulted in the discovery of a new type of activating agent other than the acidic catalysts which had previously been known in the fusion method. In the presence of an excess amount of activating agents, e.g., p-nitrophenol, the condensation reaction of theophylline with 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose proceeded, even in the absence of p-toluenesulfonic acid, to give the corresponding nucleoside. Some of the activating agents were found to form molecular compounds with theophylline, and a few of the latter to afford the corresponding nucleoside similarly. A possible mechanism for the activation process of theophylline by the above agents was discussed.

Among various nutritional mutants with weak 5′-nucleotidase derived from Bacillus subtilis IAM 1145, the adenine-requiring mutants could convert exogenously added hypo- xanthine, guanine, xanthine and their ribosides to 5′-inosinic acid (IMP) and accumulate it in the medium. Synthesis of IMP from purine derivatives was observed predominantly in an early stage of the cultivation. The conversion was stimulated by Fe2+ or Mn2+, and markedly depressed by an excess amount of adenine in the production-medium.

The solubilizing effects of N-methylated cyclic ureides, purine derivatives and bile acid salts on aromatic hydrocarbons were studied by reversed-phase chromatography. Systems containing 1-(2,3-dihydroxypropyl)-theobromine and 1,3,7,9-tetramethyluric acid in the mobile phase and di-n-butyl ether or decahydronaphthalene in the stationary phase were suitable for the practical separation of aromatic hydrocarbons.

Several 2- and 5-substituted oxazolo[5,4-d]pyrimidines have been prepared from 5-amino-4-cyanooxazole derivatives via N-ethoxymethylene intermediates in order to compare them with purine derivatives. Spectroscopic data and some chemical properties of these compounds were examined. A convenient method for the preparation of a starting material was described.

1-Phenyl-5, 6-diaminouracil (IX) or-2-thiouracil (X) prepared from 1-phenyl-6-aminouracil (V) or 1-phenyl-6-amino-2-thiouracil (VI) in an usual way was fused with urea or thiourea to yield 3-phenyluric acid and 3-phenylthiouric acid derivatives (XII, XIII, XIV and XV), while it was reacted with formamide to afford 3-phenylxanthine derivatives (XX and XXI), and with nitrous acid to give triazolo-derivatives (XXIV and XXV). Acetylation of IX or X resulted in formation of the corresponding 5-acetyl derivatives (XXVII and XXVIII) which on heating at 230∼240° as the sodium salts were converted into 8-methylpurine derivatives (XXIX and XXX). Preliminary anti-cancer testing results of the purine derivatives synthesized were described.

The rate at which uric acid is turned out of the body is very different at different times of the day, even when the food contains no ready-made purine derivatives. It is higher during the early hours of the day than at anytime, and it is considerably lower at night. The reason for this, as was pointed out by one of us, is not likely to be that the excretory functions are depressed at night, since these functions, to judge from the total nitrogen of the urine, are more active during the first hours of sleep than at any time in the 24 hours. And since, when the diet is confined to bread, butter, and milk, the uric acid must be derived from the body substance and not from the food, it seems probable that there is some function of the body which is in abeyance during sleep and is, to a considerable degree, responsible for the output of uric acid; some function, that is to say, which is effected by chemical reactions involving the production of uric acid, and possibly in some measure creatinine. If it is possible to identify this function, the activity of which can, on a suitable diet, be measured by the amount of the uric acid excreted, it may be possible to give a clearer account of the processes by which, at the onset of fever, the temperature of the body can be sent up independently of any voluntary muscular activity; for while the temperature is rising, the output of uric acid may be four times as great as it otherwise would be. Similarly, in the study of other pathological conditions in which uric acid plays a part, it must be of importance to be able to point to the kind of activity which is accompanied by increased uric acid production.

Purinderivate mit einem 2-Hydroxy-3-halogenpropyl-Substituenten an N-7 werden dargestellt; die Struktur der Seitenkette wird sowohl durch chemische Methoden als auch durch 1H-NMR-Spektren aufgezeigt. Ihre Umsetzung mit Aminen fuhrt zu Aminoalkoholen, die identisch mit den bei der aminolytischen Spaltung von Hexahydro-oxazolopurinen isolierten Verbindungen sind. 7-[2-Hydroxy-3-halogenopropyl]-tetrahydropurines and their Reaction with Amines Purine derivatives with a 2-hydroxy-3-halogenopropyl substituent at N-7 are synthesized; the structure of the side chain is proved by chemical methods and 1H–NMR-spectra. The reaction with amines affords amino alcohols; these and the compounds isolated in the aminolytic cleavage of hexahydro-oxazolopurines are identical.

In the PMR spectrum of 8-phenylpurines, the multiplet of the o-protons appears downfield of the multiplet, characteristic for m,p-protons. The separation of the centres of these two signals (Δ-value) diminishes with increasing steric interference between the phenyl ring and substituents in the imidazole moiety. The contribution of the purine ring current to the chemical shifts of the aromatic protons was calculated according to the theory of Johnson and Bovey, and the torsion angles θ between the phenyl ring and the plane of the purine system were derived. For 8-phenylpurines with an NH-group in the imidazole ring, θ is 10–15°; for compounds with an N-methyl group in this ring, θ ≈ 35–45°; in 3,9-dimethyl derivatives, Δ becomes zero, while θ is about 50°.

Syntheses of xanthine, 3,7-, 1,3- and 1,7-diethyl- and of 3- and 7-monoethyl-xanthines are described in this publication

The experimental results of the photochemical transformation of purine, adenine, hypoxanthine and caffeine were tested by using two different sets of parameters in the HMO formalism. Net charges and bond orders are in accord with the photochemical reactivities of caffeine and purine, while for the other cpds. examined the agreement is less satisfactory. The perturbation index ASP (atom -self-polarisability) gives a good estimate of the reaction site, while predictions with Fukui's frontier orbital theory are less adequate.

When zeatin was supplied to radish seedlings with roots excised, a number of metabolites were formed. These included adenine, adenosine, adenosine 5′-phosphate, zeatin riboside and zeatin riboside 5′-phosphate. However the major metabolite was a glucoside of zeatin which differed from 9-β-D-glucopyranosylzeatin. This metabolite termed raphanatin, which is active as a cytokinin, occurred mainly in the cotyledons of the seedlings.

Summary The authors studied the use of chloranilic acid as a reagent in the paper chromatography of various nitrogenous compounds, such as aromatic and aliphatic amines, amides, and guanidine, pyridine and purine derivatives. The sensitivity was found to vary from 2 to 6 μg in most cases, and from 10 to 50 μg for the purine alkaloids.

6-Dimethylamino-9-[2-acetoxy-athyl]-purin (1), 6-Dimethylamino-9-[2-acetoxy-propyl]-purin (2), 6-Dimethylamino-9-[3-acetoxy-propyl]-purin (3), N-[2-Acetoxy-athyl]-benzimidazol (4), 2-Dimethylamino-athylacetat (5), 1-Dimethylamino-isopropylacetat (6) und 3-Dimethylamino-propylacetat (7) werden synthetisiert. Mit Hilfe der Hydroxylamin-Reaktion werden die Ester in ihrer Reaktivitat verglichen: Die Purin-Derivate sind im Vergleich zum Essigsaureathylester nur wenig aktiviert und unterscheiden sich nicht vom Benzimidazol-Derivat. Lediglich der induktive Effekt des tertiaren Stickstoffs bewirkt eine Steigerung der Reaktionsgeschwindigkeit bei der Umsetzung mit Hydroxylamin. Dies ist besonders deutlich bei den Estern von Dimethylamino-alkoholen. On the Reactivity of Acetate Esters of Nitrogen Containing Alcohols 6-Dimethylamino-9-[2-acetoxy-ethyl]-purine (1), 6-dimethylamino-9-[2-acetoxy-propyl]-purine (2) and 6-dimethylamino-9-[3-acetoxy-propyl]-purine (3) are synthesized. The rate of their reaction with hydroxylamine is compared to that of N-[2-acetoxy-ethyl]-benzimidazole (4), 2-dimethylamino-ethyl acetate (5), 1-dimethylamino-isopropyl acetate (6) and 3-dimethylamino-propyl acetate (7). The purine derivatives react with hydroxylamine faster than ethyl acetate but far more slowly than the aliphatic esters of dimethylamino alcohols. Acetoxyethylpurine and the benzimidazole derivative show the same reaction rate with hydroxylamine. Evidently only the tertiary nitrogen of the imidazole part is responsible for the activation of the ester linkage. The relatively high reactivity of the aliphatic esters is explained by the stronger inductive effect of a non-heterocyclic nitrogen.

One pyrimidine and nine purine derivatives were studied in vitro against T. cruzi. Concentrations of 1/750 to 1/30,000 inhibited the trypanosomes studied manometrically and also in cultures both aerobically and anaerobically. 2,6-diamino purine hydrate appeared to be the most active of the agents studied.

During the course of studies on the effects of mutation in carbohydrate metabolism on the synthesis of purine derivatives, it was found that three mutants of a Bacillus species, which lacked transketolase or d-ribulose 5-phosphate 3-epimerase, accumulated a large amount of d-ribose in the culture medium. The amount of d-ribose was about 35 mg per ml of the broth incubated for 6 days. d-Ribose in the broth was purified in crystalline form and was identified from its chemical and physical properties.

Aus Purinderivaten mit einem Halogensubstituenten an C-8 und einer 3-Hydroxy-2-halogenpropyl-Seitenkette an N-7 werden in alkalischem Medium durch Ringschlus Hexahydro-oxazinopurine erhalten. 1H–NMR-Daten dieser Verbindungen werden mitgeteilt. Synthesis of Halogen-substituted Hexahydro-oxazinopurines From purine derivatives with a halogen substitutent at C-8 and a 3-hydroxy-2-halogenopropyl side chain at N-7, hexahydro-oxazinopurines are synthesized by ring closure in alkaline solution. 1H–NMR spectral data of these compounds are given.

Alkyl and glycosyl migration reactions of N-1, N-3, N-7 and N-9 substituted derivatives of adenine, N6, N6-dimethyladenine, N2-acetylguanine and purine were demonstrated. In addition, the chemical shifts of these derivatives in nuclear magnetic resonance (NMR) were determined and the frontier π-electron densities of nitrogens in purine ring were calculated by simple LCAOMO method. These results provided the order of thermodynamical stability and kinetical favour of the derivatives on the alkylation reaction.

Heating of the sodium salt of 4-amino-5-acylamino-6-mercaptopyrimidine results in the formation of a purine derivative but its heating with dilute hydrochloric or sulfuric acid was found to give thiazolo[5, 4-d]pyrimidine derivatives. 5-Amino-6-mercaptopyrimidine derivatives react with nitrile to form thiazolo[5, 4-d]pyrimidine derivatives, while they react with monochloroacetic acid to form pyrimido[4, 5-b][1, 4]thiazine derivatives, and with nitrous acid to form thiadiazolo[5, 4-d]pyrimidine derivatives.

The review deals mainly with the discussion of the synthesis of purine derivatives based on the interaction between uric acid and acetic anhydride. Problems of the structure, intermediates in the reaction, N-methylated derivatives of the compounds, and their conversion into 8-methylxanthines are discussed. Much attention has been devoted to the synthesis of 9-methylpurine derivatives from uric acid using 1,3,8,9-tetramethylxanthine as an intermediate. Various methods of synthesising N-methylated purines substituted in the 8-position have been described. The bibliography includes 157 references.

To see if polar movement was typical of growth-regulators other than auxins, the movement of adenine-8-(14)C and of kinetin-8-(14)C was studied in segments cut from petioles of increasing age. No polarity was found. In time-course experiments lasting 24 hr, kinetin showed a progressive increase of radioactivity in receiver blocks, while adenine showed a maximum at 8 hr with a decline thereafter. More kinetin moved through older segments than through younger ones. There was no difference in net loss as far as the position of the donor block is concerned. However, the loss of radioactivity from adenine donor blocks was much higher than the loss of radioactivity from kinetin donor blocks.The radioactivity in receiver blocks after 24 hr treatment with kinetin-(14)C was still with kinetin, judging by location on chromatograms. By the same criterion, adenine and a smaller amount of some other compound were in receiver blocks after a 6 hr transport with adenine-(14)C in the donors. By contrast, more zones of radioactivity were extracted from petiole segments to which kinetin or adenine had been added. For both purine derivatives the original compound represented no more than 20% of the total radioactivity extracted from the tissue after a transport period of 24 hr.