Structure and biosynthesis of kendomycin, a carbocyclic ansa-compound from Streptomyces

Kendomycin [(-)-TAN 2162] 1 was re-isolated from Streptomyces violaceoruber (strain 3844-33C) in the course of our chemical screening programme. The structure with the relative configuration only was confirmed by the X-ray analysis of 1. The absolute configuration of 1 was determined by using the advanced Mosher's ester method applied to kendomycin acetonide 2. The biosynthesis of 1 was performed using stable isotope labelling experiments. From the results it is assumed that a highly oxygenated benzoic acid, derived from (3,5-dihydroxyphenyl)acetic acid, serves as the starter unit of the aliphatic polyketide chain. The cyclisation generating the 18-membered ansa-bridge by the formation of a C-C bond might follow a new type of aldol condensation. 1 and 2 exhibit antibacterial activity and strong cytotoxicity against different tumor cell lines.