Synthesis of a library of stereo- and regiochemically diverse aminoglycoside derivatives

Abstract

A library of forty modified aminoglycosides was prepared in which the configuration and regiochemistry of two or three rings was widely varied. The library was based around three core ring systems: the 2-deoxystreptamine ring system found in the natural products, and both enantiomers of (1R*,2R*,4R*,5R*)-2,5-diamino-cyclohexane-1,4-diol and (1R*,3R*,4R*,6R*)-4,6-diaminocyclohexane-1,3-diol. In each case, the core was modified by glycosylation with one or two sugar rings. The absolute configuration of the sugar substituents (d or l), the configuration of the anomeric centres (alpha or beta), and the regiochemical arrangement of the amine(s) were varied.