Mannopeptimycins, Novel Antibacterial Glycopeptides from <i>Streptomyces </i><i>h</i><i>ygroscopicus</i>, LL-AC98

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 (<b>1</b>−<b>5</b>), 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 <b>2</b> and to mannosyl monosaccharide and disaccharide moieties in <b>1</b>, <b>3</b>, <b>4</b>, and <b>5</b>. The presence and position of an isovaleryl group in the terminal mannose (Man-B) in <b>3</b>−<b>5</b> are critical for retaining antibacterial potency.