Band 19, Heft 5

Xanthines are a widely known group of alkaloids, commonly used as bronchodilators and psycho and cardiac stimulants. Most of their actions are principally connected with either antagonism of adenosine receptors or phosphodiesterase inhibition; nevertheless, other profiles of their biological activity – antiviral, antitumor or anticancer – are also known. Here, we present a review of the main synthetic methods to obtain xanthine-derived heterocyclic fused systems. The five-, six- or seven-membered heterocyclic ring is attached to the purine-2,6-dione core with one or two bridgehead (ring junction) nitrogen atoms. The biological activity profile of the individual heterocyclic systems is mentioned.

After a long history of medical and biochemical investigations of vitamin B 1 , N -heterocyclic carbenes (NHCs) have recently been used as organocatalysts for a variety of synthetic reactions. This review article highlights the application of NHC-catalyzed reactions including enantioselective reactions to the heterocyclic synthesis. NHC-catalyzed benzoin condensation and Stetter reaction of ether- and amine-linked aldehydes give four- to six-membered oxygen and nitrogen heterocycles. NHC-catalyzed conjugate additions of enals to ketones and imines afford γ-lactones and γ-lactams. When the NHC-catalyzed reaction intermediates of enals are protonated, the reaction of the resulting enols with enones and ene-imines furnish formal hetero-Diels-Alder products. Acyl fluoride and esters can be activated by NHCs, and subsequent aldol and Michael reactions give β-lactones. Oxidation of intermediates derived from enals or the intermediates from ynals provide unsaturated acyl azolium which are transformed into cyclic products via subsequent nucleophilic reactions. NHCs also catalyze [2+2] cycloadditions of ketenes and other heterocumulenes and ring expansion of cyclic aldehydes.

An efficient approach to the synthesis of 1-methylimidazo[4,5- b ]pyridine derivatives 5–10 of biological interest has been developed. The key intermediate product 4 is obtained by cyclization of 2-amino-3-methylaminopyridine ( 3 ) with phenylacetic acid.

Small libraries of 1-(2-pyridyl)imidazolidin-2-one and 1-(2-pyridyl)-2,3,7,8-tetrahydro-1 H -imidazo[2,1- b ]- [1,3,5]triazepin-5(6 H )-one derivatives were prepared from substituted pyridine or quinoline N -oxides and 2-chloro-4,5-dihydroimidazole by means of the α-ureation and α-amination reactions. The α-ureation reaction of pyridine and quinoline N -oxides was studied theoretically by means of quantum chemical calculations at the density functional theory level. The newly obtained compounds were screened for their potential in vitro cytotoxic activity against human tumor cell lines LCLC-103H, 5637 and A-427.

A series of novel 3-substituted coumarinyl-triazine derivatives were designed and synthesized from 3-carboxycoumarins via consecutive Knoevenagel and Pinner reactions in water. All synthesized compounds were characterized by IR, 1 H NMR, 13 C NMR, MS, and elemental analysis. Further, in vitro screening was carried out against four bacterial strains ( Staphylococcus aureus, Bacillus subtilis, Escherichia coli , and Salmonella typhi ) and two fungal strains ( Aspergillus niger and Aspergillus clavatus ).

Two series of s -triazines linked with piperazine or aniline scaffolds ( 4a–i and 5a–j ) were synthesized and evaluated for their in vitro biological efficacy against Gram positive and Gram negative bacteria ( Klebsiella pneumoniae MTCC 109, Pseudomonas aeruginosa MTCC 741, Staphylococcus aureus MTCC 96, Bacillus cereus MTCC 619) and fungi ( Candida albicans MTCC 183 and Aspergillus niger MTCC 282) using a broth dilution technique. Compounds most active against certain bacteria and fungi are 4e , 4g , 4i , 5d , and 5i .

Treatment of 2-(perfluoroalkyl)aniline with 2-tolylmagnesium bromide or chloride or their substituted analogs yields an acridine containing a shorter perfluoroalkyl group at the 9 position and devoid of the methyl group of the Grignard substrate. Interestingly, no acridine is produced in an attempted reaction with aryl magnesium bromide without the ortho methyl group. With 2-fluoro-6-methylphenylmagnesium bromide the methyl group is eliminated and the fluorine is retained in the acridine product. Results of the mechanistic studies strongly suggest that loss of the methyl group occurs as methanol during air oxidation and hydrolysis of the intermediate products during aqueous workup.

A series of pyrazolines 4a–h has been synthesized by Michael addition of chalcones 3a–h with hydrazine hydrate in the presence of sodium acetate under conventional heating or microwave irradiation. Structures of the newly synthesized pyrazolines 4a–h have been established on the basis of IR, 1 H, 13 C NMR and mass spectral data.

All possible aza analogs of azulene, containing from one to three nitrogen atoms in the five-membered ring or from one to five nitrogen atoms in the seven-membered ring, have been theoretically considered to obtain information about their stabilities and aromaticities. Total electronic energy and nucleus independent chemical shift (NICS) data have been used to evaluate stability and aromaticity, respectively. The stabilities of the structures are strongly affected by the positions of the nitrogen atoms. Calculations of azaazulenes show that stability is decreased with close proximity of the nitrogen atoms. When nitrogen in the five-membered ring is adjacent to a ring junction, aromaticity of the cyclopentadienyl anion is reduced and that of the tropylium cation is increased. The number of nitrogen atoms affects the aromaticity of the system.