? The purpose of this research is the development of an efficient, asymmetric synthesis of the recently isolated antimicrobial agent abyssomicin C which was identified while screening for inhibitors of the paraaminobenzoate (pABA) biosynthetic pathway. It is postulated that abyssomicin C acts as a substrate mimic of chorismate and binds irreversibly to the enzyme aminodeoxychorismate synthase. This unique mode of action suggests that abyssomicin C may act as a highly selective antibacterial or antiprotozoic agent. The proposed synthesis features a key asymmetric inverse electron demand Diels-Alder reaction to establish the core of the natural product and an intramolecular nitrone cycloaddition to complete the macrocyclic ring. This strategy will also be employed for the preparation of abyssomicin C analogs in order to further explore the unique mode of action of this compound and delineate the biologically active pharmacophore. ? ?
|Elliott, Gregory I; Fuchs, James R; Blagg, Brian S J et al. (2006) Intramolecular diels-alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles. J Am Chem Soc 128:10589-95|