Mannopeptimycins, Novel Antibacterial Glycopeptides from Streptomyces hygroscopicus, LL-AC98

Abstract

A series of novel antibiotics with activity against methicillin-resistant staphylococci and vancomycin-resistant enterococci has been purified, and their structures have been characterized using spectroscopic analyses and chemical conversions. These antibiotics, designated mannopeptimycins α−ε (1−5), are glycosylated cyclic hexapeptides containing two stereoisomers of an unprecedented amino acid, α-amino-β-[4‘-(2‘-iminoimidazolidinyl)]-β-hydroxypropionic acid (Aiha), as a distinguishing feature. The cyclic peptide core of these antibiotics is attached to a mannosyl monosaccharide moiety in 2 and to mannosyl monosaccharide and disaccharide moieties in 1, 3, 4, and 5. The presence and position of an isovaleryl group in the terminal mannose (Man-B) in 3−5 are critical for retaining antibacterial potency.