793. The preparation of 4-amino- and other pteridines

Evans, R. M.; Jones, Peter G.; Palmer, P. J.; Stephens, F. F.

doi:10.1039/jr9560004106

Cited by 25 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To make [7-'5N]adenine, the imidazole ring was fashioned onto [4,6- 14N, 5-15N]triaminopyrimidine. In this intermediate, labeling of the central nitrogen among the three amino groups was achieved by nitrosation of 4,6-diaminopyrimidine with H'5N02, followed by reduction with sodium dithionite (13). [6-amino-'5N]adenine was a singlet, with no suggestion of an attendant doublet, indicating that there had been no appreciable rearrangement during the process of synthesis used for this compound (1).…”

Section: Methodsmentioning

confidence: 99%

Syntheses of all singly labeled [ ¹⁵ N]adenines: Mass spectral fragmentation of adenine

Scopes

Holtwick

Leonard

1981

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Syntheses of all five of the singly labeled ['5N]adenines are now provided. The presence or absence of twobond '5N-'H spin couplings in their 1H NMR spectra confirm the location of the isotope in each case. The fragmentation patterns in their mass spectra are indicative ofthe sequential losses ofHCN units and of CH2N2 from adenine upon electron impact.The synthesis of [6-amino-14N]adenine and [9-'5N]adenine provided useful information concerning the -fragmentation of adenine under electron impact (1). We considered that the completion ofthe synthesis ofall ofthe singly-labeled ['5N]adenines would be valuable not only in the determination ofthe total mass spectral fragmentation patterns ofadenine but also in 15N NMR spectroscopic investigations of adenine and adenine-containing molecules (24). Moreover, the additional '5N-labeled adenines could extend the value that has already been demonstrated in the study of mechanisms of heterocyclic ring rearrangements (1, 5, 6) and loci of alkylation (7). [6-amino-`5N]Adenine and [9-1'N]Adenine. These singly labeled adenines were prepared by the methods of Leonard and Henderson (1). MATERIALS AND METHODS[1-_5N]Adenine. Method A. 6-Benzylamino[1-15N]purine (1) (100 mg in 6 ml oft-butyl alcohol) was treated with 2 mol equivalents ofKMnO4 (140 mg in 5 ml ofwater). The reaction mixture was heated gently at 60-70'C for 20-25 min. Additional aqueous 10% (wt/vol) KMnO4 was added, and heating was continued for 10 min. After cooling, unreacted KMnO4 was destroyed by addition of solid NaHSO3. [3-15N]Adenine. A procedure in this laboratory that used 7-benzyladenine as an intermediate (8, 11) was adapted to 15N labeling. The starting material, 4-bromo-5-['5N]nitroimidazole, was prepared as described for the unlabeled compound (12). 4-Bromoimidazole (2.33 g) in absolute ethanol (12 ml) was cooled at 0C and carefully treated with 70% aqueous H15N03 (1 ml).The solution was evaporated in vacuo, and the residue was treated with concentrated sulfuric acid (12 ml) and heated at 90°C for 1 hr. The cooled reaction mixture was diluted carefully with cold water, and the off-white solid that deposited was collected by filtration and dried (2.51 g). Subsequent steps (8)

show abstract

Section: Methodsmentioning

confidence: 99%

Syntheses of all singly labeled [ ¹⁵ N]adenines: Mass spectral fragmentation of adenine

Scopes

Holtwick

Leonard

1981

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Compound 16 was treated with sodium hydrosulphite to give, by reduction of the nitroso group, 4,5,6-triamino-2-phenylpyrimidine 17 [30,31]. Cyclisation of 17 with aqueous glyoxal furnished 18 [31] which reacted with the suitable isocyanates to give the 1-substituted phenyl-3-(2-phenyl-pteridin-4-yl)-ureas 19 and 20.…”

Section: Resultsmentioning

confidence: 99%

“…The reaction of benzamidine chloride with a slight excess of silver salt of isonitrosomalononitrile gave 4,6-diamino-5-nitroso-2-phenylpyrimidine 16 as described in the literature [29,30]. Compound 16 was treated with sodium hydrosulphite to give, by reduction of the nitroso group, 4,5,6-triamino-2-phenylpyrimidine 17 [30,31]. Cyclisation of 17 with aqueous glyoxal furnished 18 [31] which reacted with the suitable isocyanates to give the 1-substituted phenyl-3-(2-phenyl-pteridin-4-yl)-ureas 19 and 20.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of New 2‐Phenyladenines and 2‐Phenylpteridines and Biological Evaluation as Adenosine Receptor Ligands

Giorgi¹,

Biagi

Livi

et al. 2007

Archiv der Pharmazie

View full text Add to dashboard Cite

Synthesis and biological assays of a series of 2-phenylpteridine derivatives are described to compare their affinities to adenosine receptors with those of the corresponding adenines, purposely prepared, and 8-azaadenines previously described. This study demonstrates that the enlargement of the five-membered ring of the adenine nucleus to a six-membered one is a modification that does not allow the molecules to maintain high activity towards adenosine receptors; in fact, pteridine derivatives did not show themselves to be good adenosine receptor ligands. On the contrary, N(6)-cycloalkyl- or N(6)-alkyl-2-phenyladenines showed a very high affinity and selectivity for A(1) adenosine receptors. We demonstrate also that the 9-benzyl substituent is crucial for conferring high affinity for A(3) receptors to molecules having a 2-phenyladenine-like nucleus.

show abstract

“…Subsequent refluxing of the isolated sulfinic acids with sulfuric acid afforded the desulfinated pyrimidines. 12 Alkaline hydrogen peroxide and sodium peroxide have also been used for the conversion of thioureas into ureas. 13 In this work, hydrogen peroxide was used for the desulfurization reaction of 1,3-dihydroimidazole-2-thiones in acid and neutral medium followed by hydroxymethylation at the 2-position.…”

mentioning

confidence: 99%

Synthesis of 2-Hydroxymethyl-1H-imidazoles from 1,3-Dihydroimidazole-2-thiones

Loksha¹,

El‐Barbary²,

El‐Badawi³

et al. 2003

Synthesis

View full text Add to dashboard Cite

S y n t h e s i s o f 2 -H y d r o x y m e t h y l -1 H -i m i d a z o l e s f r o m 1 , 3 -D i h y d r o i m i d a z o l e -2 -t h i o n e sAbstract: 1,3-Dihydroimidazole-2-thiones 1a-d were desulfurized by hydrogen peroxide in either acid or neutral medium to afford 1H-imidazoles 3a-d. Reaction of 3b,d with dimethylsulfamoyl chloride furnished N,N-dimethylsulfamoylimidazoles 5 and 6a,b. Lithiation of 5 and 6a,b followed by formylation and reduction yielded the 2-hydroxymethyl derivatives 7 and 8a,b. 4-Alkyl-5-cyclohexylmethyl-1H-imidazol-2-yl)methanols 9a,b were obtained by hydrolysis of 7 and 8a,b.Desulfurization of sulfur-containing compounds, including thioureas, has been achieved by using a number of different reagents. Raney nickel has being the most often employed; 1 other methods involved the use of nickel-sodium hydride complexes 2 and transition metal compounds, 3 alkali bromates and iodates, 4 nitric acid, 5 potassium superoxide, 6 oxygen and potassium tert-butoxide, 7 ozone, 8 3,3-dimethyldioxirine, 9 and a photochemical reaction involving singlet oxygen. 10,11 Alkaline hydrogen peroxide has been used for the oxidation of pyrimidine-2-thiones to the corresponding sulfinic acids. Subsequent refluxing of the isolated sulfinic acids with sulfuric acid afforded the desulfinated pyrimidines. 12 Alkaline hydrogen peroxide and sodium peroxide have also been used for the conversion of thioureas into ureas. 13 In this work, hydrogen peroxide was used for the desulfurization reaction of 1,3-dihydroimidazole-2-thiones in acid and neutral medium followed by hydroxymethylation at the 2-position. 2-(Hydroxymethyl)imidazoles are interesting starting materials and have been used in a practical synthesis of immunosuppressant compounds. 14 4-Benzyl-5-ethyl-1,3-dihydroimidazole-2-thione (1a) has been previously synthesized by Bullerwell and Lawson, 15 4-benzyl-5-isopropyl-1,3-dihydroimidazole-2-thione (1c) 16 and 5-alkyl-4-cyclohexyl-1,3-dihydroimidazole-2-thiones 1b,d 17 have been synthesized by Loksha et al. 16,17 In the present investigation we found that treatment of 1,3-dihydroimidazole-2-thiones 1a-d with hydrogen peroxide in an acidic medium afforded 1H-imidazole-2-sulfinic acids 2a-d as the major products and the desulfurized imidazoles 3a-d as the minor products. Treating compounds 1a-d with hydrogen peroxide in a neutral medium in ethanol furnished the desulfurized imidazoles 3a-d as the major products and the ethyl esters of 1H-imidazole-2-sulfinic acids 4a-d as the minor products. The imidazole-2-sulfinic acids 2a-d are somewhat stable in acidic medium and only small amounts were converted to the desulfinated imidazoles 3a-d through elimination of sulfur dioxide which is further oxidized to sulfuric acid by an excess of hydrogen peroxide. Under neutral reaction conditions in ethanol, small amounts of the initially formed sulfinic acids were esterified by the solvent to compounds 4a-d, whereas the major part of the sulfinic acids were converted to compounds 3a-d (Scheme 1). 5-Benzyl-4-ethyl-1H-imidazole (3a...

show abstract

793. The preparation of 4-amino- and other pteridines

Abstract: 12 hr., then evaporated, and the residue extracted with ethyl acetate. Evaporation of the ethyl acetate gave a gum which was chromatographed in benzene on acid-washed alumina. Elution with light petroleuni-benzene (1 : 9) and evaporation of the eluate gave bright yellow

Cited by 25 publications

References 0 publications

Syntheses of all singly labeled [ ¹⁵ N]adenines: Mass spectral fragmentation of adenine

Syntheses of all singly labeled [ ¹⁵ N]adenines: Mass spectral fragmentation of adenine

Synthesis of New 2‐Phenyladenines and 2‐Phenylpteridines and Biological Evaluation as Adenosine Receptor Ligands

Synthesis of 2-Hydroxymethyl-1H-imidazoles from 1,3-Dihydroimidazole-2-thiones

Contact Info

Product

Resources

About

793. The preparation of 4-amino- and other pteridines

Abstract: 12 hr., then evaporated, and the residue extracted with ethyl acetate. Evaporation of the ethyl acetate gave a gum which was chromatographed in benzene on acid-washed alumina. Elution with light petroleuni-benzene (1 : 9) and evaporation of the eluate gave bright yellow

Cited by 25 publications

References 0 publications

Syntheses of all singly labeled [ 15 N]adenines: Mass spectral fragmentation of adenine

Syntheses of all singly labeled [ 15 N]adenines: Mass spectral fragmentation of adenine

Synthesis of New 2‐Phenyladenines and 2‐Phenylpteridines and Biological Evaluation as Adenosine Receptor Ligands

Synthesis of 2-Hydroxymethyl-1H-imidazoles from 1,3-Dihydroimidazole-2-thiones

Contact Info

Product

Resources

About

Syntheses of all singly labeled [ ¹⁵ N]adenines: Mass spectral fragmentation of adenine

Syntheses of all singly labeled [ ¹⁵ N]adenines: Mass spectral fragmentation of adenine