Structure and biosynthesis of kendomycin, a carbocyclic ansa-compound fromStreptomyces

Kendomycin [(-)-TAN 2162] 1 was re-isolated from Streptomyces violaceoruber (strain 3844-33C) in the course of our chemical screening programme. The s tructure with the relative configuration only was confirmed by the X-ray an alysis of 1. The absolute configuration of 1 was determined by using the ad vanced Mosher's ester method applied to kendomycin acetonide 2. The biosynt hesis of 1 was performed using stable isotope labelling experiments. From t he results it is assumed that a highly oxygenated benzoic acid, derived fro m (3,5-dihydroxyphenyl)acetic acid, serves as the starter unit of the aliph atic polyketide chain. The cyclisation generating the 18-membered ansa-brid ge by the formation of a C-C bond might follow a new type of aldol condensa tion. 1 and 2 exhibit antibacterial activity and strong cytotoxicity agains t different tumor cell lines.