RESUMEN
Among 31 3,4-dihydro-s-triazinobenzimidazole derivatives tested 12 compounds showed in vitro antimicrobial activity against G+ bacteria. Best results were obtained with substances containing naphthyl or halogenated phenyl group on the triazine ring. The tested derivatives had no significant in vitro antimicrobial activity against either the used G- species or fungi.
Asunto(s)
Antiinfecciosos/farmacología , Bencimidazoles/farmacología , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Antibacterianos , Antiinfecciosos/química , Bencimidazoles/química , Pruebas de Sensibilidad Microbiana , Triazinas/químicaRESUMEN
D-Gluco- and D-xylopyranosylidene-spiro-hydantoins and -thiohydantoins were prepared from the parent sugars in a six-step, highly chemo-, regio-, and stereoselective procedure. In the key step of the syntheses C-(1-bromo-1-deoxy-beta-D-glycopyranosyl)formamides were reacted with cyanate ion to give spiro-hydantoins with a retained configuration at the anomeric center as the major products. On the other hand, thiocyanate ions gave spiro-thiohydantoins with an inverted anomeric carbon as the only products. On the basis of radical inhibition studies, a mechanistic rationale was proposed to explain this unique stereoselectivity and the formation of C-(1-hydroxy-beta-D-glycopyranosyl)formamides as byproducts. Enzyme assays with a and b forms of muscle and liver glycogen phosphorylases showed spiro-hydantoin 12 and spiro-thiohydantoin 14 to be the best and equipotent inhibitors with K(i) values in the low micromolar range. The study of epimeric pairs of D-gluco and D-xylo configurated spiro-hydantoins and N-(D-glucopyranosyl)amides corroborated the role of specific hydrogen bridges in binding the inhibitors to the enzyme.
Asunto(s)
Inhibidores Enzimáticos/síntesis química , Hidantoínas/síntesis química , Hígado/enzimología , Monosacáridos/síntesis química , Músculos/enzimología , Fosforilasas/antagonistas & inhibidores , Compuestos de Espiro/síntesis química , Amidas/síntesis química , Amidas/química , Inhibidores Enzimáticos/química , Hidantoínas/química , Enlace de Hidrógeno , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Conformación Molecular , Monosacáridos/química , Fosforilasa a/antagonistas & inhibidores , Fosforilasa b/antagonistas & inhibidores , Compuestos de Espiro/química , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
We studied the mass spectrometric behaviour of peracetylated and underivatized anomeric hexopyranosyl azides and 5-thioglucopyranosyl azides by means of different mass spectrometric techniques. The unstable molecular ions fragment predominantly by losing either N3 radical or N2 molecule. Loss of N2 molecule and the protonation of the derived nitrene were characteristic of the studied compounds. The presence of BF3.Et2O in the ion source is favorable for producing the protonated nitrene form. The protonated nitrene shows a new type of ring expansion rearrangement. The abundances of the [M + H - N2]+ ion makes it possible to identify the anomeric configuration of the azido group.
Asunto(s)
Azidas/química , Espectrometría de MasasRESUMEN
For the synthesis of the threefold-branched pentasaccharide, O-alpha-D-mannopyranosyl-(1----3)-O-[(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----4)]-O-[alpha-D-mannopyranosyl-(1----6)]-O-beta-D- mannopyranosyl-(1----4)-2-acetamido-2-deoxy-D-glucopyranose (20), which is a part of the structure of the N-glycoproteins, the disaccharide 4-O-(4-O-acetyl-3,6-di-O-allyl-2-O-benzyl-beta-D-mannopyranosyl) -1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranose was synthesized as a key compound by use of the silver silicate-catalyst procedure. After elimination of the 4-O-acetyl group, a 2-acetamido-2-deoxy-beta-D-glucopyranosyl group was attached according to the phthalimido method. Further elimination of the allyl groups allowed the linkage of two alpha-D-mannopyranosyl groups in the presence of mercury salt. A deblocking sequence consisting of four steps gave 20.