Cytosaminomycin C

Streptomyces amakusaensis KO-8119, a soil isolate, was found to produce a series of new anticoccidial compounds. Four active compounds, designated as cytosaminomycins A, B, C and D, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and preparative HPLC. Cytosaminomycins inhibited the growth of Eimeria tenella in an in vitro assay system using primary chicken embryonic cells as a host. No schizont in the cells was observed at concentrations ranging from 0.3 to 0.6 microgram/ml for cytosaminomycins A, B and C, and at 2.5 micrograms/ml for cytosaminomycin D.

Structures of novel anticoccidial antibiotics, cytosaminomycins A, B, C and D, were elucidated by NMR studies. Cytosaminomycins were shown to be nucleoside antibiotics related to oxyplicacetin. Their carboxylic acid moieties bonded to the cytosine residue were different from that of oxyplicacetin. The carboxylic acids contained in cytosaminomycins A, B, C and D were (E)-3-(methylthio)acrylic acid, 4-methylaminobenzoic acid, 3-methylcrotonic acid, and tiglic acid, respectively.

2',6'-Dideoxy-beta-D-hexopyranosyl pyrimidine nucleoside, which is a component of anticoccidal antibiotics--cytosaminomycins, was synthesized in a stereoselective manner via the intramolecular pyrimidine delivery method. Further glycosylaion of the 4'-position with a glycosyl fluoride gave the disaccharide nucleoside skeleton of the cytosaminomycins.