Isolation and Structure Elucidation of Cruentarens A and B — Novel Members of the Benzolactone Class of ATPase Inhibitors from the Myxobacterium Byssovorax cruenta

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Abstract

Two novel secondary metabolites, namely cruentaren A (1) and B (2), have been isolated from the myxobacterium Byssovorax cruenta. Their structures have been elucidated by detailed NMR spectroscopic analysis. Both compounds are isomers of a C₂₂ polyketide with a 2-hydroxy-4-methoxybenzoic acid terminus, which forms a 12-membered lactone in 1 and a six-membered lactone in 2. An amino group at C-22 is acylated by a 3-hydroxy-2-methylhexanoic acid group whose absolute configuration has been determined by GC analysis after hydrolysis and stereoselective synthesis. Degradation of 2 by olefin cross-metathesis in the presence of ethylene yields the C-12 to C-21 fragment 8, whose relative configuration has been predicted applying Kishi’s ¹³C NMR spectroscopic data base approach, and whose absolute configuration has been proven by comparison with two synthetic stereoisomers. The configuration of C-9 and C-10 has been determined by Mosher’s method and NMR spectroscopy. Degradation of cruentaren A (1) by olefin cross-metathesis in the presence of ethylene gives crystalline 21,22-seco-cruentaren (14). Its crystal structure analysis reveals the relative configuration and conformation of the macrocycle and enables solution conformation analysis. The high cytotoxic activity of 1 is essentially lost on derivatisation or rearrangement to 2.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)