Semisynthetic aminoglycoside antibacterials. Part 11. Solution conformations of semisynthetic and naturally occurring aminoglycoside antibiotics

Abstract

A critical analysis of the ¹³C n.m.r. spectral data for a wide range of naturally occurring aminoglycoside antibiotics, as well as for a diverse assortment of semisynthetic aminoglycoside antibacterials, has revealed new insights into the solution conformation of these clinically important drugs. Correlation of the Δδ_c values for C-4 and C-6 determined in going from deoxystreptamine to the pseudo di-or tri-saccharides, as well as changes in the chemical shifts of C-1′ and C-1″, has revealed that these molecules adopt a wide range of well defined conformations in solution, that are dependent not only on the structure, but also the pH. The limitations of the ‘Nagabhushan–Daniels Rule,’ which has been reported to break down when applied to some classes of aminoglycosides, are discussed in the light of these new observations.