PUROMYCIN.<sup>1</sup> SYNTHETIC STUDIES. I. SYNTHESIS OF 6-DIMETHYLAMINOPURINE, AN HYDROLYTIC FRAGMENT

Baker, B. R.; Joseph, Joseph P.; Schaub, Robert E.

doi:10.1021/jo01369a024

Cited by 51 publications

(11 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the formation of pteridines from 5-nitrosopyrimidines had proved robust and had delivered single regioisomers, this approach was adopted, in which the 4-amino group would be introduced by displacement of 4-amino-6-chloro-2-(methylthio)pyrimidine 14 ( Figure 5 ). However, displacement of the chloro group had been reported only for pyrimidine 14 , using dimethylamine to install a 4-dimethylamino group [ 26 ]. 4,6-Diamino-2-methylthiopyrimdines such as 15 would be required, and would be obtained by displacement of 14 with benzylamine derivatives or with heteroarylmethylamines ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

Pteridine-2,4-Diamine Derivatives as Radical Scavengers and Inhibitors of Lipoxygenase that can Possess Anti-Inflammatory Properties

et al. 2015

View full text Add to dashboard Cite

BackgroundReactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. The complex nature of inflammation and of oxidative stress suggests that dual-target agents may be effective in combating diseases involving reactive oxygen species.ResultsA novel series of N-substituted 2,4-diaminopteridines has been synthesized and evaluated as antioxidants in several assays. Many exhibited potent lipid antioxidant properties, and some are inhibitors of soybean lipoxygenase, IC50 values extending down to 100 nM for both targets. Several pteridine derivatives showed efficacy at 0.01 mmol/kg with little tissue damage in a rat model of colitis. 2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)pteridin-4-amine (18f) at 0.01 mmol/kg exhibited potent anti-inflammatory activity (reduction by 41%).ConclusionThe 2,4-diaminopteridine core represents a new scaffold for lipoxygenase inhibition as well as sustaining anti-inflammatory properties.

show abstract

Section: Resultsmentioning

confidence: 99%

Pteridine-2,4-Diamine Derivatives as Radical Scavengers and Inhibitors of Lipoxygenase that can Possess Anti-Inflammatory Properties

et al. 2015

View full text Add to dashboard Cite

show abstract

“…of carbon disulfide in 37 cc. of pyridine (5) for 90 minutes. The solution was evaporated to dryness in vacuo.…”

Section: -N-methylanilinopurine (Vllb) (A)mentioning

confidence: 99%

“…of dimethylaniline at the b.p. for eight hours, then work-up as described for 2-methylmercapto-4-amino-6-chloropyrimidine (5) gave 6.4 g. (53%) of product, m.p. 93-95°.…”

mentioning

confidence: 99%

Puromycin. Synthetic Studies. Vi. Analogs of 6-Dimethylaminopurine

Baker¹,

Joseph²,

Williams³

1954

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

Degradation studies on puromycin have shown that this antibiotic is a derivative of 6-dimethylamino-9-(3'-aminoribosyl)purine (1). Synthetic studies directed towards a total synthesis of this antibiotic have led to a general method for the glycosidation of 6-dimethylaminopurine on the required 9-position (2, 3). It was observed that glycosidation of the chloromercury salts of 6-dimethylaminopurine or 2,8-bis-methylmercapto-6-dimethylaminopurine occurred on the 7-position, but that of 2-methylmercapto-6-dimethylaminopurine occurred on the 9-position. A series of N-6 substituted purines are described in this communication which should prove useful for the synthesis of puromycin analogs.An elegant synthesis of 6-alkylaminopurines by reaction of 6-methylmercaptopurine with amines has been recently described by Elion, Burgi, and Hitchings (4). This synthesis has the definite advantage that from one intermediate a series of 6-alkylaminopurines can be made by one further reaction. Unfortunately, these 6-alkylaminopurines, particularly if the amine is tertiary, will orientate to the 7-position during glycosidation and would not be useful for synthesis of N-6 structural variants of puromycin. Since 2-methylmercapto-6dimethylaminopurine will orientate to the 9-position, the synthesis of this compound (I -> IX) described in an earlier paper of this series (5) has now been shown to be adaptable to the preparation of N-6 variants of 2-methylmercapto-6-dimethylaminopurine.To show the wide adaptability of this synthesis, four types of amines were selected for study, (a) another symmetrical dialkylamine, diethylamine; (b) an aryl alkyl amine, N-methylaniline; (c) a cyclic secondary amine, piperidine; and (d) an unsymmetrical dialkyl amine, benzyl-n-butylamine. The last amine serves additional useful purposes discussed later.The reaction of the chloropyrimidine, I, with these amines was run in refluxing Methyl Cellosolve1 in the case of diethylamine and piperidine, whereas direct fusion was employed for the higher-boiling benzyl-n-butylamine and N-methylaniline. In all cases the yields of diamines, II, were good. The nitrosation reaction to III was varied in concentration of acetic acid in water depending upon the solubility of the diamines. Reduction to the non-crystalline triamines, V, was efficient with sodium hydrosulfite in 50% acetone. The crude triamines were immediately reacted with 90 % formic acid giving the 5-formamidopyrimidines, VI, as crystalline solids.2 Cyclization to the desired 2-methylmercapto-6-dialkyl-

show abstract

“…The values of µ 1 , µ 2 , µ 3 , were calculated as averages of three measurements. 2-Thio-6-aminouracil was obtained according to literature [17,18].…”

mentioning

confidence: 99%

New isomeric 2‐ortho‐(meta‐ and para‐) chloro‐(bromo and nitro‐)benzylthio‐6‐aminouracils

Wyrzykiewicz

Szponar

2001

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

Ten new ortho, meta and para substituted derivatives of 2-benzylthio-6-aminouracils have been prepared. Electron Impact (EI) induced mass spectral fragmentation of these compounds was investigated. Fragmentation pathways are proposed on the basis of accurate mass and metastable transition measurements. The correlation between the intensities of the M +. and the selected fragment ions of these compounds is discussed. The data obtained create the basis for dinstinguishing isomers. The 1 H and 13 C NMR spectra of these compounds were assigned unambiguously using a combination of heteronuclear (HETCOR) spectra the chemical shifts. The data derived from these spectra can be used to differentiate the isomers.

show abstract

PUROMYCIN.¹ SYNTHETIC STUDIES. I. SYNTHESIS OF 6-DIMETHYLAMINOPURINE, AN HYDROLYTIC FRAGMENT

Cited by 51 publications

References 4 publications

Pteridine-2,4-Diamine Derivatives as Radical Scavengers and Inhibitors of Lipoxygenase that can Possess Anti-Inflammatory Properties

Pteridine-2,4-Diamine Derivatives as Radical Scavengers and Inhibitors of Lipoxygenase that can Possess Anti-Inflammatory Properties

Puromycin. Synthetic Studies. Vi. Analogs of 6-Dimethylaminopurine

New isomeric 2‐ortho‐(meta‐ and para‐) chloro‐(bromo and nitro‐)benzylthio‐6‐aminouracils

Contact Info

Product

Resources

About

PUROMYCIN.1 SYNTHETIC STUDIES. I. SYNTHESIS OF 6-DIMETHYLAMINOPURINE, AN HYDROLYTIC FRAGMENT

Cited by 51 publications

References 4 publications

Pteridine-2,4-Diamine Derivatives as Radical Scavengers and Inhibitors of Lipoxygenase that can Possess Anti-Inflammatory Properties

Pteridine-2,4-Diamine Derivatives as Radical Scavengers and Inhibitors of Lipoxygenase that can Possess Anti-Inflammatory Properties

Puromycin. Synthetic Studies. Vi. Analogs of 6-Dimethylaminopurine

New isomeric 2‐ortho‐(meta‐ and para‐) chloro‐(bromo and nitro‐)benzylthio‐6‐aminouracils

Contact Info

Product

Resources

About

PUROMYCIN.¹ SYNTHETIC STUDIES. I. SYNTHESIS OF 6-DIMETHYLAMINOPURINE, AN HYDROLYTIC FRAGMENT