Synthesis of quinoxalines and benzoquinoxalines with potential pharmacologic activity

GLISONI R.J.; FERNANDEZ B.M.; MOGLIONI A.

Molecular Medicinal Chemistry

INSTITUTO DE INVESTIGACIÓN DE LAS CIENCIAS EXACTAS FÍSICAS Y NATURALES

Año: 2007 vol. 13 p. 19 - 21

1666-888X

Some 3-quinoxalin-2-one carboxylic acids (I) and its esters showed some anticancer activity, further revealing moderate antibacterial and antifungal activity (Di Nardo et al., 1984; Sanna et al., 1998; Vitale et al., 1998). Moreover, 3-alkyl substituted derivatives of quinoxalin-2(1H)-one (II) proved to have a similar moderate anti-tumor activity (Sanna et al., 1999). The introduction of a benzene ring in the quinoxalinone (III) resulted in the corresponding benzoquinoxalinone (IV), which showed activity on human lung tumor cells (EKVX cell line), human kidney tumor cells (LC A498), and on tumor cells of the central nervous system (SNB-75 line) (Rodrigo et al., 1997). Furthermore, the search for effective agents for the AIDS treatment is an open field of research in medicinal chemistry. In that sense, compounds with different chemical structures have been prepared, including quinoxalines, which act as non-nucleoside inhibitors of HIV reverse transcriptase. On the basis of these considerations the organic synthesis of quinoxalinones and benzoquinoxalinones was carried out by the traditional method of Hinsberg (1887). Since the conventional reaction of Hinsberg shows difficulties for the preparation of quinoxalinic heterocycles and produces, when the benzene ring is substituted, a mixture of position isomers very difficult to separate, an alternative synthetic route of quinoxaline derivatives was explored: a reaction of biocatalysis using yeasts. This technique led to yields of 90-95%, while the amount used as starting material was not a limiting factor for this reaction, but it is for the traditional Hinsberg reaction. Furthermore, it has been observed that the enantioselective reactions were possible when using the enzymatic route, thus leading to a unique final product of higher purity, and hence to higher yields.The biocatalysis is a new synthetic route that uses the enzymatic machinery of some species of microorganisms to carry out reactions of oxidation-reduction, condensation, acylation and cyclization, among others. This new approach has the advantage of being economic and less toxic than the traditional routes, since the reactions occur in aqueous layer and not in organic solvents. In addition, the induction of the enzymes of interest can be achieved, in case of obtaining low yields, as well as also the inhibition of other enzymes that give secondary products of reaction.