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

Liebigs Annalen
1997.0

Abstract

<jats:title>Abstract</jats:title><jats:p>The myxobacterial metabolites chivosazole A (<jats:bold>1</jats:bold>) and its variants (<jats:bold>2–6</jats:bold>) were discovered in <jats:italic>Sorangium cellulosum</jats:italic>, strain So ce12, which simultaneously provides the broad spectrum antibiotic sorangicin as well as the sorangiolides and disorazoles. The antifungal and cytotoxic chivosazoles (<jats:bold>1–6</jats:bold>) 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 (<jats:bold>7</jats:bold>), was formed by strain So ce885 and showed similar activity antibiotic and cytotoxic.<jats:p>The biogenetic origin of the structural elements in chivosazole F (<jats:bold>7</jats:bold>) was studied by feeding experiments with [1‐<jats:sup>13</jats:sup>C]‐, [1,2‐<jats:sup>13</jats:sup>C]acetate, [<jats:italic>methyl</jats:italic>‐<jats:sup>13</jats:sup>C]methionine and [1‐<jats:sup>13</jats:sup>C]serine. Accordingly, the aglycon <jats:bold>7</jats:bold> 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 <jats:italic>N</jats:italic>‐acetyl unit form the 1,3‐oxazole ring. C‐ and <jats:italic>O</jats:italic>‐methyl groups are derived from methionine.

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