De novo macrolide-glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles.

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.

Synthesis and evaluation of antimigratory and antiproliferative activities of lipid-linked [13]-macro-dilactones.

The biological activities of a family of novel, lipid-linked 13-membered-ring macro-dilactones are reported. These [13]-macro-dilactones were synthesized by diacylation of functionalized diols, followed by ring-closing metathesis under conditions we had previously reported. Antimigratory, cytostatic and cytotoxic activities of the compounds against cancer cells were evaluated. Compound 13 was the most potent in the series, while compound 10 had the broadest concentration range of subtoxic antiproliferative activity. These compounds share common structural components, namely the [13]-macro-dilactone templated by an octyl alpha-glucoside 4,6-diol.