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‐ 13 C]‐, [1,2‐ 13 C]acetate, [ methyl ‐ 13 C]methionine and [1‐ 13 C]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.