Stereochemical integrity of oxazolone ring-containing jadomycins

The jadomycins are a series of natural products produced by Streptomyces venzuelae ISP5230 in response to ethanol shock. A unique structural feature of these angucyclines is the oxazolone ring, the formation of which is catalyzed by condensation of a biosynthetic aldehyde intermediate and an amino acid. The feeding of enantiomeric forms of α-amino acids indicates that the amino acid is incorporated by S. venezuelae ISP5230 without isomerization at the α-carbon. The characterization of the first two six-membered E-ring-containing jadomycins is reported. These precursor-directed biosynthesis studies indicate flexibility in the acceptor substrate specificity of the glycosyltransferase, JadS. Analysis of cytotoxicity data against two human breast cancer cell lines indicates that the nature of the substitution at the α-carbon, rather than the stereochemistry, influences biological activity.