Microwave assisted synthesis of 6-Substituted aminopurine analogs in water

Abstract

Aminação de derivados de 6-cloropurina em água, assistida por microondas, resultou na preparação de análogos de aminopurina 6-substituídas, em bons rendimentos. Usando um forno de microondas simples, modificado com aparelhagem para refluxo, a aminação do 6-cloro na estrutura da purina ocorreu em condições brandas. Foram preparados 19 análogos conhecidos e 16 desconhecidos de aminopurinas substituídas, através de substituição aromática nucleofílica com filtração simples ou coluna de cromatografia.Microwave assisted amination of 6-chloropurine derivatives with various amines in water resulted in a "green chemistry" protocol for the preparation of 6-substituted aminopurine analogs in very good yields. Using a simply modified microwave oven with the refluxing apparatus, the amination of the 6-chloro in the purine structure occurred smoothly. 19 known and 16 unknown 6-substituted aminopurine analogs were prepared through nucleophilic aromatic substitution with simple filtration or column chromatography.Keywords: amination, 6-substituted aminopurine analogs, nucleophilic substitution, microwave irradiation, amines IntroductionIn modern antiviral and antitumor therapy, an important role is played by modified nucleosides and their analogs, in which modified purine structures are frequently found.1,2 6-Substituted aminopurine analogs, the aminated products of the 6-functional groups in purine structures, continued focusing attention due to their wide range of biological activities (inhibitors of Clostridium feseri growth, 3 cytokinin activity, 4 CIV-CDK (CIV1) and Candida albicans as antifungal medicines, 5 selective kinase, 6 agonists of the A 1 adenosine receptor, 7 the cysteine protease cathepsin K, 8 and platelet aggregation 9 ). Prominent examples of synthetic 6-substituted aminopurine analogs are N-cyclopentyl adenosine (CPA) and N-cyclohexyl adenosine (CHA) (two agonists for the adenosine A 1 receptors). 10The traditional method for the synthesis of 6-substituted aminopurine analogs is the amination of halo, ). However, the complete conversion usually needs 2-24 h and the use of toxic organic solvents or relatively expensive reagents could not be avoided, which dose not conform to the requirement of modern pharmaceutical industry and environmental friendliness.In any case, the development of efficient protocols for the synthesis of aminopurine analogs is still an important goal. Mild reaction conditions, short reaction times and high selectivity and yields are preferable, which makes us pay attention to microwave irradiation. Microwave assisted organic synthesis and functional group conversions have been an increasingly popular field as indicated by numerous publications in the past few years.17 It often leads to rate enhancement, higher yields, easier work-up and better selectivity as well as shortening reaction times compared with the conventional heating methods. In spite of the body of literature about microwave accelerated organic synthesis, the references on the microwave-assisted synthesis of nucleoside com...

Synthesis and Antifungal Activities of Some Novel Pyrimidine Derivatives

“…Using POCl 3 as chlorination reagent [ 16 ], the intermediate 4-chloro-2-isopropyl-6-methyl-pyrimidine was synthesized and used for the next substitution directly without purification in a small-scale synthesis. Reacting 4-chloro-2-isopropyl-6-methylpyrimidine with the corresponding aminesin different solvents afforded 3a [ 17 ], 3b [ 18 ] and 3c [ 19 ], however, it was not necessary to use K 2 CO 3 in the preparation of 3a . In the preparation of compound 4a , the 4-morpholinecarbonyl chloride must be prepared freshly before use.…”

Exploiting the roles of nitrogen sources for HEA increment in Cordyceps cicadae

“…Therefore, it has attracted much attention for its potential application in the medical industry, especially in the field of cancer therapy. Currently, HEA has been obtained mainly by chemical synthesis ( Qu et al, 2006 ) and liquid fermentation mycelium extraction ( Qu et al, 2006 ). However, chemical synthesis of HEA involves multiple steps, low yields and expensive raw materials, hindering its synthesis on an industrial scale.…”

General Approach to N6,C5′-Difunctionalization of Adenosine

“…Generally, the conditions used for these transformations are variations of those originally described, , involving reaction of 6-ClP-riboside or the 2′,3′,5′-tri- O -acetyl-protected version with the amine, in an alcohol solvent (e.g., EtOH, MeOH, PrOH) or DMF, either with or without a base (e.g., CaCO 3 , BaCO 3 , Et 3 N, iPr 2 NEt, etc.). More recently, microwave-induced amination in water has also been described …”

“…More recently, microwave-induced amination in water has also been described. 11 Use of 6-bromopurine riboside (6-BrP-riboside) for such reactions is rare, but specifically, its 2′,3′,5′-tri-O-acetyl derivative readily reacted with alkyl amines at room temperature in 1,2-DME. 12 On the other hand, reaction with imidazole proceeded in DMF, and those with p-toluidine and o-anisidine proceeded in MeOH, EtOH, and DMF, at 65 °C.…”