Synthesis and biological characterization of arylomycin B antibiotics.

ABSTRACT

Antibiotics are virtually always isolated as families of related compounds, but the evolutionary forces underlying the observed diversity are generally poorly understood, and it is not even clear whether they are all expected to be biologically active. The arylomycin class of antibiotics is comprised of three related families that are differentiated by nitration, glycosylation, and hydroxylation of a conserved core scaffold. Previously, we reported the total synthesis of an A series member, arylomycin A2, as well as the A series derivative arylomycin C16 and showed that both are active against a broader spectrum of bacteria than previously appreciated. We now report the total synthesis of a B series analogue, arylomycin B-C16, and its aromatic amine derivative. While the aromatic amine loses activity against all bacteria tested, the B series compound shows activities that are similar to the A series compounds, except that it also gains activity against the important pathogen Streptococcus agalactiae.