title: Design and synthesis of a structurally constrained aminoglycoside.
abstract: The synthesis of a constrained tricyclic aminoglycoside derivative is described. This constrained compound fixes the spatial orientation of two critical rings for the minimal motif for binding to biological macromolecules such as RNA and proteins. Methanolysis of neomycin B under acidic conditions produced the bicyclic neamine. Transient protection by the Cu2+ ion and regioselective introduction of protective groups led to intermediate 7, which was used for a key annulation reaction that introduced the tricyclic nucleus into the structural framework. A final hydrogenolysis step to remove the protective groups produced the desired target molecule. The efficient eight-step synthesis was accomplished in 8% overall yield.
authors.affiliation: Department of Chemistry and Biochemistry, University of otre Dame, Notre Dame, Indiana 46556, USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Kling
authors.forename: Dusan
authors.initials: D
authors.lastname: Hesek
authors.forename: Qicun
authors.initials: Q
authors.lastname: Shi
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D000617:Aminoglycosides