Making Complanadine A

Two groups have independently synthesized the alkaloid complanadine A for the first time (J. Am. Chem. Soc., DOI: 10.1021/ja101893b and 10.1021/ja101956x). Although each team used a different strategy to attain the molecule—which is found in a small, creeping plant known as club moss—both relied on transition metals.

Complanadine A aids production of nerve growth factors, something of interest in regenerative medicine and Alzheimer’s disease research. But the molecule is too scarce to study in depth.

Captivated by complanadine A’s activity and intricate structure, organic chemists Richmond Sarpong of the University of California, Berkeley, and Dionicio Siegel of the University of Texas, Austin, set out to make it. Complanadine A is a dimer, but the attachment point differs on each of its two halves. Sarpong and Daniel F. Fischer made the natural product via an iridium-catalyzed C–H functionalization and a Suzuki coupling. Siegel, Changxia Yuan, and colleagues opted for two cobalt-catalyzed [2+2+2] cycloadditions. Both teams are working to make larger quantities and analogs.

These “exceptionally efficient and elegant” syntheses showcase the power of transition metals, says Hidetoshi Tokuyama, an expert on alkaloid synthesis at Tohoku University, in Japan.

When the teams learned that they were working on the same target, they ended up having several helpful discussions, Siegel says. “Perhaps the bigger story here is that two academics in a competitive field worked together to ensure that both papers were published back to back,” Sarpong adds.