Natural products provide potential drug candidates, but the synthetic route to a natural product can be difficult to achieve. A recent breakthrough was reported by researchers at the Scripps Research Institute in La Jolla, California, who successfully synthesized palua'amine, a complex alkaloid that has shown potential as a possible anticancer, antibacterial, and antifungal agent. The compound is derived from a sponge off Palau, an island nation in the Pacific Ocean. The compound was discovered in 1993, but the complexity of the molecule has made its synthesis very challenging, according to a Jan. 7, 2010, Scripps Research Institute press release.
The compound has eight contiguous stereogenic centers, several reactive nitrogen-containing moieties, and a highly strained core that forms a junction between two five- membered rings (3). Scripps Research chemist Phil Baran, who led the team that made the breakthrough, has been working on the synthesis since he arrived as a faculty member at Scripps Research more than six years ago, according to the release.
Another group of researchers at Scripps Research Institute reported on a strategy for aryl carbon–hydrogen olefination, an approach that may be useful for synthesizing natural products and other drugs. The palladium-catalyzed Mizoroki–Heck reaction, which couples aryl halides with olefins, is widely used to forge carbon–carbon bonds (5). But this approach has certain disadvantages, namely installing the halide of interest is not always easy, according to a Dec. 3, 2009 Scripps Research Institute release. An alternative method, palladium-catalyzed carbon–hydrogenation olefination, has been limited to specific cases that generally include electron-rich heterocyles and/or stoichiometric palladium (5). The researchers instead used a carboxylate-directed palladium (II)-catalyzed carbon–hydrogen olefination reaction using phenylacetic acid and 3-phenylpropionic acid substrates with oxygen at atmospheric pressure as the oxidant and amino-acid derivatives as the ligands. This approach was used to produce commercial drug scaffolds and to synthesize 2-tetralone and naphtholic acid natural product cores (5).