Antibiotics from Gliding Bacteria, LXXX. Chivosazoles A–F: Novel Antifungal and Cytotoxic Macrolides from Sorangium cellulosum (myxobacteria)

The myxobacterial metabolites chivosazole A (1) and its variants (2–6) were discovered in Sorangium cellulosum, strain So ce12, which simultaneously provides the broad spectrum antibiotic sorangicin as well as the sorangiolides and disorazoles. The antifungal and cytotoxic chivosazoles (1–6) are novel glycosides of 6‐deoxyglucopyranose derivatives and an aglycon that includes an oxazole in its 31‐membered macrolide ring. The aglycon itself, chivosazole F (7), was formed by strain So ce885 and showed similar activity antibiotic and cytotoxic. The biogenetic origin of the structural elements in chivosazole F (7) was studied by feeding experiments with [1‐13C]‐, [1,2‐13C]acetate, [methyl‐13C]methionine and [1‐13C]serine. Accordingly, the aglycon 7 is a polyketide assembled by condensation of nine acetate units, one serine unit and a further seven acetate units. While C‐1 of serine is part of the macrolide ring, the amido to hydroxyl part of the serine together with C‐1 of the adjacent N‐acetyl unit form the 1,3‐oxazole ring. C‐ and O‐methyl groups are derived from methionine.