Biosynthetic studies of ottelione A and the structural re-analysis of the "Jones isomers"; the structural reassignment of Phomopsichalasin to that of Diaporthichalasin

Abstract

Part 1 Ottelione A, isolated from the fresh water plant Ottelia alismoides, is a cytotoxic agent at nanomolar levels against 60 human cancer cell lines. Among other compounds isolated were a group of novel 1,7-diarylheptanoids. We propose that one of these diarylheptanoids shares a biogenetic linkage with ottelione A. Namely, we hypothesize that a spontaneous (i.e., non-enzyme catalyzed) Cope rearrangement, almost entirely unprecedented in nature, is central to the biosynthesis of ottelione A. The successful synthesis of the hypothesized biologically relevant diarylheptanoid has now enabled us to probe its possible biogenetic linkage to ottelione A. During the course of our studies we have also performed the structure reanalysis of two related hydrienone compounds that share the exact same core as ottelione A. Part II Phomopsichalasin, a cytochalasin-like secondary metabolite, was isolated from an endophytic fungus Phomopsis sp. in 1995. Diporthichalasin, from the endophytic fungus Diaporthe sp. Bkk3, was isolated several years later in 2007. Both were assigned different structures and their spectroscopic characterization reported in two different solvents. By way of detailed NMR analysis and pertinent computational models we have demonstrated that the structure originally proposed for Phomopsichalasin was incorrect and is in fact that of the more recently isolated compound Diaporthichalasin.