Synthesis of Potential Anticancer Agents. XIII. Ribosides of 6-Substituted Purines

Johnson, James A.; Thomas, H. Jeanette; Schaeffer, Howard J.

doi:10.1021/ja01536a044

Cited by 86 publications

(45 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three methods have been reported in the literature for the synthesis of 6-azido-9-β- d -ribofuranosylpurine. The oldest method involves conversion of 6-chloro-9-β- d -ribofuranosylpurine to an unstable 6-hydrazino derivative followed by treatment with nitrous acid 16. The acidic conditions are obviously not compatible with the labile 2′-deoxyribonucleosides.…”

Section: Resultsmentioning

confidence: 99%

“…In a second method, 6-methylsulfonyl-9-β- d -ribofuranosylpurine was converted to the azidopurine nucleoside 17. It has been noted in these reports that displacement of chloride from 6-chloro-9-β- d -ribofuranosylpurine by azide ion results in decomposition 16,17. Consistent with these observations, more recent syntheses of 6-azido-9-β- d -ribofuranosylpurine18 and 6-azido-9-β- d -arabinofuranosylpurine19 by replacement of chloride with azide gave low 21% and 38.4% yields of the respective azidopurine nucleoside derivatives.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Azide−Tetrazole Equilibrium of C-6 Azidopurine Nucleosides and Their Ligation Reactions with Alkynes

et al. 2010

View full text Add to dashboard Cite

Facile syntheses of C-6 azidopurine ribonucleosides and 2′-deoxyribonucleosides have been developed. For silyl and acetyl protected as well as unprotected nucleosides, access to the azido derivatives could be readily attained via displacement of BtO − from the O 6 -(benzotriazol-1-yl) inosine nucleosides by azide anion. Use of diphenylphosphoryl azide/DBU as a simple route to the acetyl-protected azido nucleosides was also evaluated, but this proved to be inferior. Since these azido nucleosides can exist in an azide•tetrazole equilibrium, the effect of solvent polarity on this equilibrium was investigated. Subsequently, a detailed analysis of Cu-mediated azide-alkyne ("click") ligation was undertaken. Biphasic CH 2 Cl 2 /H 2 O medium proved to be best for the ligation reactions, suppressing the undesired azide reduction that was competing. Interestingly, although the tetrazolyl isomer predominates (ca 80%) in CD 2 Cl 2 and in CD 2 Cl 2 /D 2 O, the Cu-catalyzed click reactions proceed smoothly with the silyl-protected ribo and 2′-deoxyribonucleosides, leading to the C-6 triazolyl products in good to excellent yields. Thus, depletion of azido form from the reaction mixture shifts the azide•tetrazole equilibrium, eventually resulting in complete consumption of azide and tetrazole. In several cases, major and minor azide-alkyne ligation products were observed and characterization data are provided for both. In order to confirm the regiochemistry leading to the major isomer, one product was crystallized and evaluated by X-ray crystallography. The Cucatalyzed azide-alkyne ligation is clearly efficient and significantly superior to thermal reactions, which were slow. Biological evaluation showed low cytotoxicities for the agents, suggesting their usefulness as biological probes.* To whom correspondence should be addressed. Tel.: (212) 650-7835; fax: (212) 650-6107. lakshman@sci.ccny.cuny.edu. Supporting Information Available: General experimental details, materials and methods for antiproliferative tests and the results, ORTEP of 4b, copies of 1 H and 13 C NMR spectra of 2c, 2d, 3a-f, 4a-g, 4f′, 5a-g, 5a′, 5c′-f′, 6a-6g and 7a-7g. This information is available free of charge via the Internet at

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Azide−Tetrazole Equilibrium of C-6 Azidopurine Nucleosides and Their Ligation Reactions with Alkynes

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The 1 H NMR and UV spectra were identical to those reported previously. [22] N 6 -Methyladenosine (3c): N 6 -Methyladenosine was synthesised by a procedure modified from that of Johnson et al [23] Accordingly, a solution of 6-chloropurine riboside (0.78 mmol; 250 mg) in aqueous methylamine (40%, 12.5 mL) was heated in a Parr reactor at 70°C and 1.5 bar for 16 hours. The solution was concentrated down to a small volume, and the precipitate was filtered.…”

Section: Methodsmentioning

confidence: 99%

Reactions of Adenosine with Bromo- and Chloromalonaldehydes in Aqueous Solution: Kinetics and Mechanism

et al. 2000

View full text Add to dashboard Cite

“…This solution was frozen and lyophilized to give 1.09g (quantitative) of a photosensitive white powder. The lH nmr spectrum of this powder indicated an equilibrium of two products (6-azidoe cyclic tetrazole) (23 B. Alternatively, this reaction can be completed in 1.5h at room temperature using 0.6g (10.2mmol) of Me3N and 1.0g (15.4 mmol) of NaN, with 0.5g (1.2mmol) of 7 in 30mL of acetonitrile.…”

Section: -(235-tri-0-acetyl-j3-d-ribofuranosy1)-2-amino-6-azido-mentioning

confidence: 98%

Nucleic acid related compounds. 33. Conversions of adenosine and guanosine to 2,6-dichloro, 2-amino-6-chloro, and derived purine nucleosides

Robins¹,

Uznański²

1981

Can. J. Chem.

136

View full text Add to dashboard Cite

Enzymatic deamination of adenosine 1-N-oxide gave 1-hydroxyinosine (2a) which was acetylated and then chlorinated to give 2,6-dichloro-9-(2,3,5-tri-O-acetyl-(β-D-ribofuranosyl)purine (3). Ammonia in dry 1,2-dimethoxyethane converted 3 into 2-chloro-adenosine triacetate (4a). Treatment of 4a with trimethylamine at elevated temperatures in acetonitrile resulted in formation of 2-N,N-dimethylaminoadenosine triacetate (4b). Guanosine (5) was acetylated smoothly by an improved procedure. The resulting triacetate (6) was chlorinated in ∼85% yield to give 2-amino-6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (7). Treatment of 7 with trimethylamine at ambient temperature for 28 hours gave the 6-N,N-dimethylamino compound (8d). However, potassium fluoride or sodium azide with catalytic quantities of trimethylamine in DMF or acetonitrile gave the 2-amino-6-fluoro (8a) or 2-amino-6-azido (8b) products in yields of greater than 90%.

show abstract

Synthesis of Potential Anticancer Agents. XIII. Ribosides of 6-Substituted Purines

Abstract: The syntheses of six 6-substituted-9-,B-~-ribofuranosplpurines from 6-chloro-9-P-~-ribofuranosylpurine have been accomplished.i o 0

Cited by 86 publications

References 7 publications

Azide−Tetrazole Equilibrium of C-6 Azidopurine Nucleosides and Their Ligation Reactions with Alkynes

Azide−Tetrazole Equilibrium of C-6 Azidopurine Nucleosides and Their Ligation Reactions with Alkynes

Reactions of Adenosine with Bromo- and Chloromalonaldehydes in Aqueous Solution: Kinetics and Mechanism

Nucleic acid related compounds. 33. Conversions of adenosine and guanosine to 2,6-dichloro, 2-amino-6-chloro, and derived purine nucleosides

Contact Info

Product

Resources

About