Glycopeptide antibiotics have been attracting much interest owing to their activity against methicillin-resistant Staphylococcus aureus. Many new glycopeptides have been reported, but only vancomycin has been used clinically. It has excellent antibacterial activity but some problems remain with its intravenous administration, the most important being the side-effect of the so-called red man's syndrome and the presence of undesirable minor components. Here we report the structures of newly isolated vancomycin-type antibiotics, orienticins, and their derivatives. Orienticins were found in the metabolites of a microorganism identified as Nocardia orientalis PA-42867 and suggested to be new glycopeptides by preliminary chromatographic experiments. They are mainly composed of two components, A and B, which can be easily separated according to Scheme 1. Comparison of 1H NMR (in DMSO-d6, DMSO-d6+D2O; at 60°C, 80°C, 100°C) with vancomycin showed orienticin A has an aglycone composed of N-methylleucine and asparagine as vancomycin but two amino sugars epimeric to vancosamine at C-4 and lacks Cl substitution at the C-aromatic ring; orienticin B has the same amino sugar at the A-l' carbon (δC 74.1 (d)) but a neutral sugar linked to glucose. Structures were supported by 13C NMR and secondary ion mass spectroscopy (SI-MS), which gave satisfactory (M+H)+ values: A (C73H89N10O26Cl+H) 1557, B (C72H86N9O27Cl+H) 1544. Acid hydrolysis at lower temperatures allowed selective cleavage of sugar moieties without aglycone rearrangement (asparagine to isoaspartate), isolating 4-epi-vancosamine (purified as methyl 4-epi-vancosamine diacetate), D-glucose (by optical rotation), and L-olivose (from orienticin B). The aglycone configurations of orienticin A and vancomycin were confirmed to be the same by circular dichroism (CD) and hydrogenation experiments (vancomycin's aglycone hydrogenated on Pd-C in acetic acid gave a product identical to orienticin A's aglycone). Additional minor components C and D were isolated, with structures deduced by NMR and SI-MS. Catalytic hydrogenolysis of orienticin A gave orienticin C as expected. In vitro antibacterial activities of orienticins and vancomycin are summarized in Table 1. After completion of this work, eremomycin having properties very similar to those of orienticin A was reported without disclosing the chemical structure.