Structural and biosynthetic investigations of the rubromycins

Abstract

The structure of the known secondary metabolite beta-rubromycin was corrected, 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 verified, but the identity of the starter unit and the folding mechanism of the polyketide chain are still unclear. From the culture broth of the strain A1, in addition to 6, the co-metabolites gamma-rubromycin (3), delta-rubromycin (4) and 3'-hydroxy-beta-rubromycin (7) were isolated. Their structures were determined or confirmed by detailed spectroscopic analysis. The rubromycins inhibit HIV-1 reverse transcriptase (RT) and are cytostatically active against different tumor cell lines.