Total Synthesis of the Polycyclic Fungal Metabolite (± )-Communesin F

摘要

In 1993, Numata et al. isolated two unique natural products from a Penicillium mold, which was found growing on the marine alga Enteromorpha intestinalis. The structures of these compounds, communesin A (1) and communesin B (5), were determined by spectroscopic analysis (Scheme 1). Nota- ble features of these complex, highly functionalized polycyclic metabolites are the two contiguous quaternary centers at C7/ 8, and the presence of the two aminal moieties. The communesins were found to have cytotoxic activity against P-388 lymphoid leukemia cells in vitro. In 2001, Hemscheidt and co-workers described an alkaloid called nomofungin, which was isolated from an unidentified fungus growing on the bark of Ficus microcarpa in Hawaii. This material was found to have cytotoxic activity against LoVo and KB cells, which resulted from the ability of the metabolite to cause microfilament disruption. The initial structural assignment of this metabolite, however, was incorrect, and nomofungin was in fact found to be communesin B (5). Notably, however, Hemscheidt and co-workers established the configuration at C21 of 5, together with the absolute configuration of the molecule; these structural features were not originally determined by the Numata group. More recently, several other structurally modified communesin derivatives have been isolated, including communesin C (6), D (7), E (2), F (8), G (3), and H (4). Some of these new compounds were found to have significant biological activity. For example, communesins D, E, and F are insecticidal, and communesins C and D are moderately active against various leukemia cell lines.