3013-82-9Relevant academic research and scientific papers
Regiospecific N9 alkylation of 6-(heteroaryl)purines: Shielding of N7 by a proximal heteroaryl C-H
Zhong, Minghong,Robins, Morris J.
, p. 8901 - 8906 (2006)
Purine alkylations have been plagued with formation of mixtures of N9 (usually desired), N7, and other regioisomers. We have developed methods for synthesis of 6-(azolyl)purine derivatives whose X-ray crystal structures show essentially coplanar conformations of the linked azole-purine rings. Such ring orientations position the C-H of the azole above N7 of the purine, which results in protection of N7 from alkylating agents. Treatment of 6-(2-butylimidazol-1- yl)-2-chloropurine (9) with sodium hydride in DMF followed by addition of ethyl iodide resulted in exclusive formation of 6-(2-butylimidazol-1-yl)-2-chloro-9- ethylpurine (10), whereas identical treatment of 2-chloro-6-(4,5- diphenylimidazol-1-yl)purine (11) produced a regioisomeric mixture 12/13 (N9/N7, ～5:1). The linked imidazole and purine rings are coplanar in 9 (the butyl side chain is extended away from the purine ring and C-H is over N7) but are rotated ～57° in 11, and the more bulky azole substituent in 11 did not prevent formation of the minor N7 regioisomer 13. Access to various regioisomerically pure 9-alkylpurines is now readily available.
A new approach to the synthesis of N,N-dialkyladenine derivatives
Alves, M. Jose,Carvalho, M. Alice,Carvalho, Silvia,Dias, Alice M.,Fernandes, Francisco H.,Proenca, M. Fernanda
, p. 4881 - 4887 (2008/03/14)
N,N-Dialkyladenine derivatives were prepared by two different reaction sequences starting from 5-amino-4-cyanoformimidoylimidazoles. When these imidazoles were treated with dimethylformamide diethyl acetal, a 5-aminomethyleneamino-4-cyanoformimidoylimidazole was isolated and evolved to the N,N-dialkyladenine in the presence of a secondary alkylamine. The same purine structure was isolated when the 5-amino-4-cyanoformimidoylimidazole was first treated with a secondary amine to give a stable 4-amidino-5- aminoimidazole. The desired product was generated when the 4-amidino-5- aminoimidazole was combined with dimethylformamide diethyl acetal, at room temperature. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
Nucleic acid related compounds. 86. Nucleophilic functionalization of adenine, adenosine, tubercidin, and formycin derivatives via elaboration of the heterocyclic amino group into a readily displaced 1,2,4-triazol-4-yl substituent
Miles, Robert W.,Samano, Vicente,Robins, Morris J.
, p. 5951 - 5957 (2007/10/02)
Treatment of 9-methyladenine and hydroxyl-protected derivatives of adenosine and 2′-deoxyadenosine with 1,2-bis[(dimethylamino)methylene]hydrazine and/or its dihydrochloride at elevated temperatures in appropriate solvents resulted in elaboration of the 6-amino group into a 6-(1,2,4-triazol-4-yl) substituent in excellent yields. Analogous functionalization of the amino groups of tubercidin {4-amino-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]-pyrimidine} and formycin {7-amino-3-(β-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine} gave the respective 4- and 7-(1,2,4-triazol-4-yl) derivatives. Nucleophilic replacement of the triazole moiety gave the respective 6-, 4-, and 7-substituted purine, pyrrolo[2,3-d]pyrimidine, and pyrazolo[4,3-d]pyrimidine products. This first general method for "direct" nucleophilic replacement of an amino group on these nitrogen heterocycles also provides a new class of compounds for potential postsynthetic modifications after incorporation into oligonucleotides.
Pattern of OH Radical Reaction with N6,N6,9-Trimethyladenine. Dehydroxylation and Ring Opening of Isomeric OH Adducts
Vieira, A. J. S. C.,Steenken, S.
, p. 9340 - 9346 (2007/10/02)
The OH radical reacts with N6,N6,9-trimethyladanine (A) in aqueous solution by addition to carbons 4 and 8 of the purine system (k = 8.4 * 109 M-1 s-1).The resulting radicals A4OH* and A(OH* undergo elimination of OH(1-) (identified by conductance; kel = 2*106 s-1) and ring opening (k = 2.3*105 s-1), respectively.The two types of reaction have different activation parameters.The (heterolytic) dehydroxylation reaction of A4OH* is inhibited by H(1+) and by OH(1-).The radical cation (the yield per OH* is 50percent) formed by elimination of OH(1-) from A4OH* is oxidizing (with respect to N,N,N',N'-tetramethyl-p-phenylenediamine); in contrast, A8OH* or its ring-opened product is reducing (toward tetranitromethane or viologens).On one-electron oxidation, A8OH* is converted into 8-hydroxy-N6,N6,9-trimethyladenine, which was measured by HPLC with optical and electrochemical detection.
6-(Alkylamino)-9-benzyl-9H-purines. A New Class of Anticonvulsant Agents
Kelley, James L.,Krochmal, Mark P.,Linn, James A.,McLean, Ed W.,Soroko, Francis E.
, p. 606 - 612 (2007/10/02)
Several 9-alkyl-6-substituted-purines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats.Most compounds were prepared in three steps from 5-amino-4,6-dichloropyrimidine or in two steps via alkylation of 6-chloropurine.Potent anticonvulsant activity against MES resided in compounds that contain a benzyl substituent at the 9-position of 6-(methylamino)- or 6-(dimethylamino)purine.Among commonly used agents for control of seizures, this type of structure represents a new class of potent anticonvulsant agents.
SYNTHESES OF N,N,3- AND N,N,9-TRIALKYLADENINES BY ALKYLATION OF N,N-DIYLKYLADENINES
Itaya, Taisuke,Matsumoto, Hiroo,Ogawa, Kazuo
, p. 1920 - 1924 (2007/10/02)
Alkylation of N,B,N-dimethyl- (Ia) and N,N-diethyladenine (Ib) with methyl iodide, ethyl iodide, and benzyl bromide in N,N-dimethylacetamide in the presence of potassium carbonate gave the corresponding N,N,9-trialkyladenines (II) in 54-74percent yields, as well as minor amounts of N,N,3-trialkyladenines (III).The alkylation of I without base gave the latter compounds (III) in 76-90percent yields.Keywords - N,N,3-tryalkyladenines: N,N,9-trialkyladenines; regioselective N-alykaltion; N,N-dialkyladenines; isomer ratio.
