Stereospecific synthesis of methyl 2-amino-2,4-dideoxy-6S-deuterio-α-D-xylo-hexopyranoside and methyl 2-amino-2,4-dideoxy-6S-deuterio-4-propyl-α-d-glucopyranoside: Side chain conformation of the novel aminoglycoside antibiotic propylamycin

Abstract

The stereospecific syntheses of methyl 2-amino-2,4-dideoxy-4-C-propyl-α-d-glucopyranoside and of methyl 2-amino-2,4-dideoxy-α-D-xylo-hexopyranoside and of their 6S-deuterioisotopomers are described as models for ring I of the aminoglycoside antibiotics propylamycin and 4′-deoxyparomomycin, respectively. Analysis of the 1H NMR spectra of these compounds and of methyl 2-amino-2-deoxy-α-d-glucopyranoside, a model for paromomycin itself, reveals that neither deoxygenation at the 4-position, nor substitution of the C–O bond at the 4-postion by a C–C bond significantly changes the distribution of the side chain population between the three possible staggered conformations. From this it is concluded that the beneficial effect on antiribosomal and antibacterial activity of the propyl group in propylamycin does not derive from a change in side chain conformation. Rather, enhanced basicity of the ring oxygen and increased hydrophobicity and/or solvation effects are implicated.