Spirangien Derivatives from the Myxobacterium Sorangium cellulosum: Isolation, Structure Elucidation, and Biological Activity

Abstract

AbstractIn addition to spirangiens A (1) and B (2), 11 new spirangiens have been isolated from the myxobacterium Sorangium cellulosum (strain So ce90). Spirangiens A and B consist of a polyketide backbone with a spiroketal core, 13 stereocenters, and a conjugated pentaene chromophore with a terminal carboxylic acid. The structures of the derivatives were elucidated on the basis of NMR and MS data. The stereochemistry was determined by 1D and 2D NMR experiments as well as by biosynthetic studies. Four derivatives 6–9 differ in the cis/trans double‐bond geometry of the pentaene chromophore side‐chain and four of them (4–6 and 10) are characterized by the absence of methoxy groups. Derivative 13 does not exhibit the spiroketal core due to reduction of the acetalic carbonyl group. In addition, 11 and 12 exhibit the opposite configuration at C‐20 compared with the known spirangiens A and B. Derivative 3 contains an additional hydroxy group at the end of the side‐chain. All the new spirangien derivatives, as well as spirangiens A and B, were tested in cytotoxicity assays against two different cell lines and showed strong cytotoxic activity. Even though spirangien A was identified as the most cytotoxic compound, other derivatives, such as 3, 4, 6, and 10, showed significantly higher activity against the KB‐3‐1 cell line than against the nontransformed cells (L‐929).