Conformations of fortimicins and three-dimensional structure-activity relationship in the aminoglycoside antibiotics

N Hirayama, K Shirahata, Y Ohashi and Y Sasada

The fortimicins are pseudodisaccharide antibiotics consisting of purpurosamine and fortamine moieties which are connected through an alpha-linkage. NMR spectra indicate that the fortamine ring in fortimicin A takes a chair conformation which corresponds to an inverted one in the conformation of fortimicin B free base. Fortimicin A is unstable in solution, and we were unable to obtain any crystals of it. To elucidate the structure of fortimicin A and to clarify the stereochemistry of fortimicins, we have undertaken to calculate their empirical force-fields starting from the X-ray structures of fortamines and fortimicin B free base. Nuclear Overhauser enhancement data were also employed to confirm the calculated relative orientation of the two rings around the glycosidic linkage. The 3-dimensional structure- activity relationship of aminoglycoside antibiotics is discussed on the basis of these results.

Volume 23, Issue 1, pp. 127-132, 01/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics