Reações de carbociclização radicalar de meta-iodobenzamida derivada de D-galactose visando à sintese de benzomacrolactamas, potencias agentes bioativos

Abstract

Macrocycles display remarkable biologic activities and many of these compounds, or their derivatives, are used as drugs, among them, erythromycin, ciclosporin, vancomycin and anphotericin B. Among macrocycles with biological activities, there are the macrolactams, asvicenistatin, ascomycin, pimecrolimus, and others. Although macrocycles synthesis is considered one of the greatest challenges in organic synthesis, the immense chemical diversity and the bioactive potential of these compounds have been stimulating their synthesis investigation. Different methodologies can be used for macrocycles synthesis, among them, the tri-n-butyltin hydride-mediated radical carbocyclization reaction.To investigate the carbohydrates role and their stereochemistry in macrocyclizations by tri-nbutyltin hydride, as well as the influence of the groups directly involved in the cyclization reaction and their relative position in the carbohydrate, the research group of Laboratório de Química Farmacêutica/Faculdade de Farmácia/UFMG, in partnership with Departamento de Química/ ICEx/UFMG (QF/DQ/UFMG), have been developing researches related to benzomacrolactams synthesis by tri-n-butyltin hydride-mediated radical carbocyclization reaction.Carrying on this research program, it was synthesized the m-allyloxyiodobenzamide methyl 4-Oallyl- 2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)-a-D-galactopyranoside (GAX), which wasundergone to Bu3SnH-mediated radical carbocyclization reactions. Four reactions of GAX with Bu3SnH were carried out, in different conditions (reagents concentration and addition time, solvent). Macrolactams were not isolated from any reaction. The acyclic reduction product, methyl4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-benzoylamino-a-D-galactopyranoside (GAXC) was isolated from three reactions. In one of the reactions, which the reagents dilution and addition time were bigger than in other reactions, it was got an unexpected and unheard product, methyl 4-O-allyl-2,3-di-Obenzyl- 6-deoxy-6-(3-phenylbenzoylamino) -a-D-galactopyranoside (GAXD). This product was formedby attack of aryl radical from GAX on benzene, the reaction solvent.The structures of the synthesized compounds were elucidated by their IR and NMR spectra (1H,13C and 2D experiments). It was also obtained the high resolution mass spectra of GAX, GAXC and GAXD. The m-allyloxyiodobenzamide GAX, the products isolated from radical reactions (GAXC and GAXD), GA6 and GA7 were undergone to antibacterial and antifungal tests and did not show any activity.