Spirangien A and B, highly cytotoxic and antifungal spiroketals from the myxobacterium Sorangium cellulosum:: Isolation, structure elucidation and chemical modifications

Two novel highly cytotoxic metabolites, spirangien A (1) and B (2), were isolated from the myxobacterium. Sorangium cellulosum (strain So ce90). The structures were elucidated by detailed NMR spectroscopic analysis. The previously unknown molecular framework common to spirangien A and B includes a highly functionalized spiroketal core structure, a side chain bearing a pentaene chromophore and a terminal carboxyl group, and a total of thirteen stereocenters. The absolute configuration at C-3 was determined by degradation and subsequent fragment analysis by GC. The relative stereochemistry of the spiroketal structure was proposed on the basis of vicinal proton couplings and ROESY data for hydroperoxide derivative 4, obtained by ozonolysis of spirangien A, and for 1,3-diene 5, obtained by cross-metathesis with ethylene. X-ray crystal structure analysis of 5 confirmed its structure and unambiguously provided the complete relative stereochemistry of all twelve stereocenters. The 1,3-diene derivative 5 still shows strong cytotoxic activity. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.