ABSTRACT
This work demonstrates trivalent tris-(3-N-methyl-N-pyridyl propyl)amine (1) catalyzing the site-selective mono-O-acylation of glycopyranosides. Different acid anhydrides were used for the acylation of monosaccharides, mediated by catalyst 1, at a loading of 1.5 mol%; the extent of site-selectivity and the yields of mono-O-acylation products were assessed. The reactions were performed between 2 and 10 h, depending on the nature of the acid anhydride, where the bulkier pivalic anhydride required a longer duration for acylation. The glycopyranosides are maintained as diols and triols, and from a set of experiments, the site-selectivity of acylations was observed to follow the intrinsic reactivities and stereochemistry of hydroxy functionalities. The trivalent catalyst 1 mediates the reactions with excellent site-selectivities for mono-O-acylation product formation in the studied glycopyranosides, in comparison to the monovalent N,N-dimethylamino pyridine (DMAP) catalyst. This study illustrates the benefits of the multivalency of catalytic moieties in catalysis.
ABSTRACT
Pyridinoimine-functionalized poly(ether imine) (PETIM) dendrimers of 1-3 generations, possessing 4-16 moieties at the peripheries, are synthesized. Chloride-functionalized dendrimers are reacted with N-methylamino pyridine, under basic conditions, which led to functionalization of the peripheries of a dendrimer with pyridoneimine moieties. Variable-temperature 1H NMR studies are performed to assess the contributing resonance forms of pyridoneimine in the dendrimers. Solvatochromism and 15N NMR studies aid further the assessment of the contributing resonance forms. Comparison with derivatives that possess 1 and 2 pyridoneimines illustrates the contributing resonance forms between nonaromatic pyridoneimine and zwitter ionic aromatic imidopyridinium species.
ABSTRACT
The benign nature of aza-Michael addition reaction in aqueous solutions is demonstrated herein to conduct a direct glycoconjugation of amine-terminated poly(ether imine) (PETIM) dendrimers. Zero to three generations of dendrimers, possessing up to 16 amine functionalities at their peripheries, undergo aza-Michael reaction with unsaturated sugar vinyl sulfoxide in aq. MeOH solutions and afford the corresponding dendrimers modified with multiple glycosyl moieties at the periphery. First order kinetics of the glycoconjugation is monitored at varying temperatures and the rate constants are observed to be 60-508 s-1, for zero and first generation dendrimers. The antibacterial effects of amine-terminated dendrimers and the corresponding glycoconjugates are studied across Gram-positive, Gram-negative and acid-fast bacteria. Among the species, M. smegmatis and M. tuberculosis showed the greatest growth inhibition effect at micromolar concentrations, for the native amine-terminated and the corresponding glycoconjugated dendrimers. Quantitative assays are performed to adjudge the inhibition efficacies of dendrimers and the glycoconjugates. Selectivity to inhibit M. smegmatis and M. tuberculosis growth, and minimal effects on other bacterial species by dendrimers and glycoconjugates are emphasized.
ABSTRACT
A pyridoneimine-catalyzed oxa-Michael addition of protecting groups-free, native mono- and disaccharides with Michael acceptors in aq. solution is reported. Several mono- and disaccharides are reacted with acceptors, namely, methylvinyl ketone, acrylonitrile and tert-butyl acrylate in aq. solution, the addition catalyzed by n-pentylpyridone imine. The addition occurs site-selectively at the anomeric lactol and the remaining hydroxy functionalities are un-affected. The resulting keto-glycopyranoside products are explored in aldol, allylation and oxime product formation, occurring at either α-methyl moiety or at the keto-moiety, with appropriate synthons. In another direction, the keto-glycopyranoside is functionalized further with amino acids through reductive amination in aq. methanol solution. Formation of hemiacetal anion occurs in the presence of pyridoneimine in aq. Solution, enabling subsequent addition to occur with acceptors. Facile reductive amination of the resulting keto-glycoside provides an avenue for conjugations with amino acids in the present work.
Subject(s)
Disaccharides , Glycosides , Amination , Amines , Amino Acids , Catalysis , WaterABSTRACT
A site-specific deprotonation followed by alkylations and acylations of sugar hemiacetals to the corresponding alkyl glycosides and acylated sugars in aqueous solutions is disclosed herein. Pyridoneimine as a new base is developed to mediate the deprotonation of readily available sugar hemiacetals and further reactions with alkylation and acylation agents.
