Structural and biosynthetic investigations of the rubromycins

The structure of the known secondary metabolite beta-rubromycin was correct ed, based on spectroscopic and chemical investigations, from o-quinone 1 to p-quinone 6. By feeding [U-(13)C3]malonic acid to the rubromycin-producing strain, Streptomyces sp. Al, the polyketide origin of the skeleton was ver ified, but the identity of the starter unit and the folding mechanism of th e polyketide chain are still unclear. From the culture broth of the strain A1, in addition to 6, the co-metabolites gamma-rubromycin (3), delta-rubrom ycin (4) and 3'-hydroxy-beta-rubromycin (7) were isolated. Their structures were determined or confirmed by detailed spectroscopic analysis. The rubro mycins inhibit HIV-1 reverse transcriptase (RT) and are cytostatically acti ve against different tumor cell lines.