title: De novo macrolide-glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles.
abstract: Natural product-like macrocycles were designed as potential antibacterial compounds. The macrocycles featured a D-glucose unit fused into a 12- or 13-member macrolactone. The rings are connected via the C6' and anomeric (C1') positions of the monosaccharide. The new macrocycles/macrolides were characterized by X-ray crystallography. Their structures showed that, in addition to the ester and alkene units, the dihedral angle about the glycosidic linkage (exo-anomeric effect) influenced the overall shape of the molecules. Glycosylation of an available hydroxy group on the macrocycle gave a hybrid macrolide with features common to erythromycin and sophorlipid macrolactone. Weak antibiotic activity (MICs <100 μg/mL) was observed for several of the compounds.
authors.affiliation: Department of Chemistry, University of Connecticut, 55 N. Eagleville Road, U3060, Storrs, CT 06269, USA, +1-860-486-1605 FAX: +1-860-486-2981.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Desmond
authors.affiliation: Department of Chemistry, University of Connecticut, 55 N. Eagleville Road, U3060, Storrs, CT 06269, USA, +1-860-486-1605 FAX: +1-860-486-2981.
authors.forename: Anniefer N
authors.initials: AN
authors.lastname: Magpusao
authors.affiliation: Department of Chemistry, University of Connecticut, 55 N. Eagleville Road, U3060, Storrs, CT 06269, USA, +1-860-486-1605 FAX: +1-860-486-2981.
authors.forename: Chris
authors.initials: C
authors.lastname: Lorenc
authors.affiliation: Department of Chemistry and Biochemistry, University of Montana, Missoula, MT 59812, USA.
authors.forename: Jeremy B
authors.initials: JB
authors.lastname: Alverson
authors.affiliation: Department of Chemistry and Biochemistry, University of Montana, Missoula, MT 59812, USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Priestley
authors.affiliation: Department of Chemistry, University of Connecticut, 55 N. Eagleville Road, U3060, Storrs, CT 06269, USA, +1-860-486-1605 FAX: +1-860-486-2981.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Peczuh
keywords: antibiotic; carbohydrate; exo-anomeric effect; macrolide; structure; synthesis